Surbhi Sidana

All Publications

• Antibody-Based Treatment Approaches in Multiple Myeloma. Current hematologic malignancy reports Hosoya, H., Sidana, S. 2021

  Abstract

  PURPOSE OF REVIEW: The field of multiple myeloma treatment has entered a new era with antibody-based approaches in clinical practice. In this review, we focus on the clinical approaches of utilizing antibody-based modality, specifically monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell antibodies in the treatment of multiple myeloma.RECENT FINDINGS: Three monoclonal antibodies (daratumumab, isatuximab, elotuzumab) and one anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (belantamab mafodotin) have been approved by the FDA in the last 5 years for the treatment of multiple myeloma. There are many ongoing clinical trials using novel targets and constructs, including bispecific antibodies against BCMA, GPRC5D, and FCRH5. In addition to exploring efficacy, there are ongoing efforts to overcome the resistance to therapy. Antibody-based therapy has improved the outcomes of patients with multiple myeloma and has been incorporated in the standard of care. We expect to see novel targets and constructs that can achieve a deeper and more durable response while minimizing toxicity, as well as better strategies for toxicity management for existing agents. We also expect that antibody-based strategies will be used in earlier lines of therapy in the future.

  View details for DOI 10.1007/s11899-021-00624-6

  View details for PubMedID 33730360

• Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma BLOOD ADVANCES Baird, J. H., Epstein, D. J., Tamaresis, J. S., Ehlinger, Z., Spiegel, J. Y., Craig, J., Claire, G. K., Frank, M. J., Muffly, L., Shiraz, P., Meyer, E., Arai, S., Brown, J., Johnston, L., Lowsky, R., Negrin, R. S., Rezvani, A. R., Weng, W., Latchford, T., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S. 2021; 5 (1): 143–55

  View details for DOI 10.1182/bloodadvances.2020002732

  View details for Web of Science ID 000607932700016

• Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. The Lancet. Oncology Moreau, P. n., Kumar, S. K., San Miguel, J. n., Davies, F. n., Zamagni, E. n., Bahlis, N. n., Ludwig, H. n., Mikhael, J. n., Terpos, E. n., Schjesvold, F. n., Martin, T. n., Yong, K. n., Durie, B. G., Facon, T. n., Jurczyszyn, A. n., Sidana, S. n., Raje, N. n., van de Donk, N. n., Lonial, S. n., Cavo, M. n., Kristinsson, S. Y., Lentzsch, S. n., Hajek, R. n., Anderson, K. C., João, C. n., Einsele, H. n., Sonneveld, P. n., Engelhardt, M. n., Fonseca, R. n., Vangsted, A. n., Weisel, K. n., Baz, R. n., Hungria, V. n., Berdeja, J. G., Leal da Costa, F. n., Maiolino, A. n., Waage, A. n., Vesole, D. H., Ocio, E. M., Quach, H. n., Driessen, C. n., Bladé, J. n., Leleu, X. n., Riva, E. n., Bergsagel, P. L., Hou, J. n., Chng, W. J., Mellqvist, U. H., Dytfeld, D. n., Harousseau, J. L., Goldschmidt, H. n., Laubach, J. n., Munshi, N. C., Gay, F. n., Beksac, M. n., Costa, L. J., Kaiser, M. n., Hari, P. n., Boccadoro, M. n., Usmani, S. Z., Zweegman, S. n., Holstein, S. n., Sezer, O. n., Harrison, S. n., Nahi, H. n., Cook, G. n., Mateos, M. V., Rajkumar, S. V., Dimopoulos, M. A., Richardson, P. G. 2021; 22 (3): e105–e118

  Abstract

  This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.

  View details for DOI 10.1016/S1470-2045(20)30756-7

  View details for PubMedID 33662288

• Comparison of the current renal staging, progression and response criteria to predict renal survival in AL amyloidosis using a Mayo cohort. American journal of hematology Drosou, M. E., Vaughan, L. E., Muchtar, E. n., Buadi, F. K., Dingli, D. n., Dispenzieri, A. n., Fonder, A. L., Gertz, M. A., Go, R. S., Gonsalves, W. I., Hayman, S. R., Hobbs, M. A., Hwa, Y. L., Kapoor, P. n., Kourelis, T. n., Kumar, S. n., Kyle, R. A., Lacy, M. Q., Lin, Y. n., Lopez, C. L., Lust, J. A., Rajkumar, S. V., Russell, S. J., Sidana, S. n., Siddiqui, M. A., Sidiqi, M. H., Warsame, R. n., Leung, N. n. 2021

  Abstract

  Three sets of criteria (International Society of Amyloidosis (ISA), Palladini and Kastritis) were independently developed for staging, progression and response criteria to predict renal survival in patients with AL amyloidosis. We evaluated these criteria using a cohort of 495 newly diagnosed AL amyloidosis patients with renal involvement using time to event competing risk analysis at baseline, 3, 6 and 12 months after treatment. Only Palladini and Kastritis had a staging system and both predicted a higher risk of end stage renal disease (ESRD) in the stage III vs stage I patients but only Palladini model was predictive for stage II patients. At 3 months, risk of ESRD was significantly higher for Palladini and ISA renal progression (hazard ratio (HR) 2.8 (95% CI: 1.5-5.3, p=0.001) and 2.5 (CI: 1.4-4.6, p=0.004, respectively)), but renal response was not significantly protective; conversely, the risk of ESRD was not significantly higher for the Kastritis renal progression, but was significantly protective for the Kastritis renal responders (HR 0.38 (95% CI: 0.17-0.84), p=0.017). Both progression and response with ISA, Palladini and Kastritis criteria were predictive of ESRD at 6 months and 12 months. While the Palladini staging criteria at baseline, and the ISA and Palladini criteria for progression at 3 months performed better than the Kastritis criteria at baseline and 3 months post-treatment, the Kastritis criteria performed better for response 3 months after treatment. All 3 sets of criteria performed well at and after 6 months post-treatment. These differences are important when choosing endpoints for clinical trials. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26092

  View details for PubMedID 33428787

• Outcomes with different administration schedules of Bortezomib in Bortezomib, Lenalidomide and dexamethasone (VRd) as first-line therapy in Multiple Myeloma. American journal of hematology Cook, J., Johnson, I., Higgins, A., Sidana, S., Warsame, R., Gonsalves, W., Gertz, M. A., Buadi, F., Lacy, M., Kapoor, P., Dispenzieri, A., Kourelis, T., Dingli, D., Amie Fonder, P. A., Hayman, S., Hobbs, M., Hwa, Y. L., Kyle, R., Leung, N., Go, R., Rajkumar, V. S., Kumar, S. 2020

  Abstract

  Induction therapy for multiple myeloma with bortezomib (V), lenalidomide (R), and dexamethasone (d) (VRd) was traditionally administered as bortezomib given twice weekly on a 3 week cycle. A modified schedule of weekly bortezomib has been adopted over time to decrease treatment burden for patients and reduce treatment-emergent neuropathy. This study evaluates the response rates and outcomes with different schedules of bortezomib in VRd administered for first-line treatment for patient with newly diagnosed MM (NDMM). We retrospectively analyzed patients treated with upfront VRd from June 30th 2008 to December 31st 2018 for variations of bortezomib administration. Five hundred and fifty five (555) NDMM patients met inclusion criteria; median age 63years and 61% men. Bortezomib was administered twice weekly every 21days in 42%, once weekly every 21days in 41% and once weekly every 28days in 16%. Though peripheral sensory neuropathy was more frequent with twice weekly dosing (p=0.002), this group achieved shorter time to best response (p=0.01). Weekly every 21 day treatment saw higher VGPR or better rates (p=0.02). However, with median follow up time of 37 months (IQR 22-56), we found no difference in PFS or OS among the groups. While small differences in response rates were found among the varying administration schedules of bortezomib administration, there was no significant effect on PFS or OS. Given that VRd remains a first line standard of care option for newly diagnosed MM, in the absence of a large trial comparing bortezomib dosing schedule modifications, these results are helpful in supporting current practices of once weekly administration. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26074

  View details for PubMedID 33326116

• Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Lemieux, C., Johnston, L. J., Lowsky, R., Muffly, L. S., Craig, J. K., Shiraz, P., Rezvani, A., Frank, M. J., Weng, W., Meyer, E., Shizuru, J., Arai, S., Negrin, R., Miklos, D. B., Sidana, S. 2020

  Abstract

  Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (autoSCT) or allogeneic (alloSCT) transplant is not clear as there is lack of clinical trial based evidence. This single center retrospective study describes the outcomes of 16 patients with PCL (N=14 primary PCL) who underwent either autoSCT (N=9) or alloSCT (N=7) for PCL in the era of novel agents, between 2007 and 2019. Median age of the cohort was 58 years. High-risk cytogenetics were seen in 50% of patients. All patients received a proteasome inhibitor (PI) and/or immunomodulatory drug (IMiD) based regimen before transplant. At transplant, 10 (62%) patients obtained at least a very good partial response. Response after autoSCT (3 month) was at least VGPR in 6 (67%, CR=5) patients. All patients undergoing alloSCT achieved CR at 3 months. Maintenance was used in 5 patients (56%) after autoSCT. Median PFS from transplant in the autoSCT vs. alloSCT group was 6 vs. 18 months, p=0.09, while median OS from transplant was 19 vs. 40 months (p=0.41), respectively. The median OS from diagnosis was 27 vs. 49 months, p=0.50, respectively. Of all the deaths, 10 (91%) patients died of relapsed disease. In conclusion, alloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, which is comparable to other recent reports and relapse remains the primary cause of death.

  View details for DOI 10.1016/j.bbmt.2020.08.035

  View details for PubMedID 32961371

• International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials. Leukemia Costa, L. J., Derman, B. A., Bal, S., Sidana, S., Chhabra, S., Silbermann, R., Ye, J. C., Cook, G., Cornell, R. F., Holstein, S. A., Shi, Q., Omel, J., Callander, N. S., Chng, W. J., Hungria, V., Maiolino, A., Stadtmauer, E., Giralt, S., Pasquini, M., Jakubowiak, A. J., Morgan, G. J., Krishnan, A., Jackson, G. H., Mohty, M., Mateos, M. V., Dimopoulos, M. A., Facon, T., Spencer, A., Miguel, J. S., Hari, P., Usmani, S. Z., Manier, S., McCarthy, P., Kumar, S., Gay, F., Paiva, B. 2020

  Abstract

  Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

  View details for DOI 10.1038/s41375-020-01012-4

  View details for PubMedID 32778736

• Outcomes with early vs. deferred stem cell transplantation in light chain amyloidosis. Bone marrow transplantation Abdallah, N., Sidana, S., Dispenzieri, A., Lacy, M., Buadi, F., Hayman, S., Kapoor, P., Leung, N., Dingli, D., Hwa, Y. L., Lust, J., Russell, S., Gonsalves, W., Go, R., Hogan, W., Kyle, R., Rajkumar, S. V., Gertz, M., Kumar, S. 2020

  Abstract

  In the presence of effective treatment options for systemic light chain (AL) amyloidosis, autologous stem cell transplantation (ASCT) is sometimes deferred after stem cell collection. We designed this retrospective study to compare overall survival (OS) between patients who proceed directly to ASCT after stem cell collection and those who defer ASCT. We included patients with AL amyloidosis who had stem cell collection at Mayo Clinic, Minnesota, from 2004 to 2018. ASCT was considered "early" if performed within 90 days of collection, and "deferred" if performed after 90 days, or not done by last follow up. We included 651 patients; 527 underwent early ASCT and 124 deferred ASCT. There was no difference in OS with early vs. deferred ASCT (median OS: 13.0 vs. 11.4 years, respectively, P=0.28). There was no difference in OS between the 2 groups among patients with early or advanced Mayo Stage. Among patients who achieved ≥very good partial response at the time of collection, OS in the early and deferred groups was 14.2 and 13.4 years, respectively (P=0.06). Survival outcomes are similar with early and deferred ASCT. Further studies are needed to identify patients who would benefit from each approach.

  View details for DOI 10.1038/s41409-020-0964-8

  View details for PubMedID 32518290

• Quality of life (QOL), financial burden, and perception of care in patients enrolled on clinical trials (CTs). Sidana, S., Allmer, C., Larson, M. C., Dueck, A. C., Yost, K. J., Warsame, R. M., Thanarajasingam, G., Cerhan, J., Paludo, J., Rajkumar, S., Habermann, T., Nowakowski, G. S., Lin, Y., Gertz, M. A., Witzig, T. E., Dispenzieri, A., Gonsalves, W., Ansell, S. M., Thompson, C. A., Kumar, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307086

• Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM). Tam, E., Iberri, D., Liedtke, M., Muffly, L. S., Shiraz, P., Frank, M., Lowsky, R., Rezvani, A., Negrin, R., Meyer, E., Arai, S., Johnston, L. J., Shizuru, J., Weng, W., Miklos, D., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307484

• Glycosylation of Immunoglobulin Light Chains is Highly Prevalent in Cold Agglutinin Disease. American journal of hematology Sidana, S., Murray, D. L., Dasari, S., Go, R. S., Muchtar, E., Willrich, M. A., Snyder, M., Kohlhagen, M., Lust, J. A., Kourelis, T. V., Kumar, S. K., Dispenzieri, A., Gertz, M. A. 2020

  View details for DOI 10.1002/ajh.25843

  View details for PubMedID 32356376

• A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis. Blood cancer journal Sidana, S., Milani, P., Binder, M., Basset, M., Tandon, N., Foli, A., Dispenzieri, A., Gertz, M. A., Hayman, S. R., Buadi, F. K., Lacy, M. Q., Kapoor, P., Leung, N., Rajkumar, S. V., Merlini, G., Palladini, G., Kumar, S. K. 2020; 10 (4): 41

  Abstract

  Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n=473; validation cohort, Pavia: n=575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using incremental scoring based on hazard ratios with scores of 0-3 for HR (0-CR, 1-VGPR, 2-PR, 3-no response) and 0-2 for OR (0-AOR, 1-MOR, 2-NOR). Patients could be divided into two distinct CHOR groups (scores 0-3 and 4-5), with median OS in group 1 and group 2: Not reached vs. 34 months, p<0.001 [Mayo] and 87 vs. 23 months, p<0.001 [Pavia]. In conclusion, we developed a model that can assess multiple organs concurrently, and integrate both HR and OR assessments to determine early clinical benefit with treatment, which may be used as a surrogate end-point in trials and to compare outcomes with different therapies.

  View details for DOI 10.1038/s41408-020-0306-5

  View details for PubMedID 32286270

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era Muffly, L., Arai, S., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R. S., Rezvani, A., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Cunanan, K. ELSEVIER SCIENCE INC. 2020: S106

  View details for Web of Science ID 000516887900144

• Impact of Minimal Residual Negativity using Next Generation Flow Cytometry on Outcomes in Light Chain Amyloidosis. American journal of hematology Sidana, S., Muchtar, E., Sidiqi, M. H., Jevremovic, D., Dispenzieri, A., Gonsalves, W., Buadi, F., Lacy, M. Q., Hayman, S. R., Kourelis, T., Kapoor, P., Go, R. S., Warsame, R., Leung, N., Rajkumar, S. V., Kyle, R. A., Gertz, M. A., Kumar, S. K. 2020

  Abstract

  We evaluated bone marrow minimal residual disease (MRD) negativity in 44 patients with light chain (AL) amyloidosis using next generation flow cytometry (sensitivity > 1x 10-5 ; median events analyzed: 8.7 million, range: 4.8 to 9.7 million). All patients underwent MRD testing in two years from start of therapy (median: 7 months). Overall MRD negative rate was 64% (n=28). MRD-negative rate after one-line of therapy was 71% (20/28). MRD negative rates were higher with stem-cell transplant as first-line therapy (86%, 18/21) vs. chemotherapy alone as first-line treatment (29%, 2/7), p=0.005. MRD negative rate amongst patients in complete response were 75% (15/20); in very good partial response: 50% (11/22) and there were two patients in partial response/rising light chains (with renal dysfunction) who were MRD negative. There were no differences in baseline characteristics of MRD negative vs. MRD positive patients, except younger age among MRD-negative patients. MRD negative patients were more likely to have achieved cardiac response at the time of MRD assessment, 67% (8/12) vs. 22% (2/7), p=0.04. Renal response rates were similar in both groups. Progression free survival was assessed in the 42 patients achieving CR or VGPR. After median follow-up of 14 months, the estimated 1-year progression free survival in MRD negative vs. MRD positive patients was 100% (26 patients, 0 events) vs. 64% (16 patients, 5 events), p=0.006, respectively. MRD assessment should be explored as a surrogate endpoint in clinical trials and MRD risk-adapted trials may help optimize treatment in AL amyloidosis. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.25746

  View details for PubMedID 32010993

• Organ responses with daratumumab therapy in previously treated AL amyloidosis. Blood advances Chung, A. n., Kaufman, G. P., Sidana, S. n., Eckhert, E. n., Schrier, S. L., Lafayette, R. A., Arai, S. n., Witteles, R. M., Liedtke, M. n. 2020; 4 (3): 458–66

  Abstract

  Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)-free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P = .051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function.

  View details for DOI 10.1182/bloodadvances.2019000776

  View details for PubMedID 32027745

• CD22-Directed CAR T-Cell Therapy Induces Complete Remissions in CD19-Directed CAR-Refractory Large B-Cell Lymphoma. Blood Baird, J. H., Frank, M. J., Craig, J. n., Patel, S. n., Spiegel, J. Y., Sahaf, B. n., Oak, J. S., Younes, S. n., Ozawa, M. n., Yang, E. n., Natkunam, Y. n., Tamaresis, J. S., Ehlinger, Z. n., Reynolds, W. D., Arai, S. n., Johnston, L. n., Lowsky, R. n., Meyer, E. n., Negrin, R. S., Rezvani, A. R., Shiraz, P. n., Sidana, S. n., Weng, W. K., Davis, K. L., Ramakrishna, S. n., Schultz, L. n., Mullins, C. D., Jacob, A. P., Kirsch, I. R., Feldman, S. A., Mackall, C. L., Miklos, D. B., Muffly, L. n. 2020

  Abstract

  The prognosis for patients with large B-cell lymphoma (LBCL) progressing after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first three consecutive patients with autologous CAR19-refractory LBCL treated with a single infusion of autologous 1×106 CAR+ T-cells/kg targeting CD22 (CAR22) as part of a phase I dose escalation study. CAR22 therapy was relatively well tolerated, without any observed non-hematologic adverse events higher than grade 2. Following infusion, all three patients achieved complete remission, with all responses ongoing at the time of last follow up (mean 7.8 months, range 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range 85.4-350 cells/µL), and persisted beyond three months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA (ctDNA) beyond six months post-infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients who have failed prior CAR T-cell therapies. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT04088890).

  View details for DOI 10.1182/blood.2020009432

  View details for PubMedID 33512414

• Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma. Bone marrow transplantation Lemieux, C. n., Muffly, L. S., Rezvani, A. n., Lowsky, R. n., Iberri, D. J., Craig, J. K., Frank, M. J., Johnston, L. J., Liedtke, M. n., Negrin, R. n., Weng, W. K., Meyer, E. n., Shizuru, J. n., Shiraz, P. n., Arai, S. n., Miklos, D. B., Sidana, S. n. 2020

  Abstract

  We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.

  View details for DOI 10.1038/s41409-020-01026-7

  View details for PubMedID 32782351

• Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients? Sidana, S., Manasanch, E. AMER SOC HEMATOLOGY. 2019: 142–47

  View details for Web of Science ID 000538564000020

• CAR T-cell therapy: is it prime time in myeloma? Sidana, S., Shah, N. AMER SOC HEMATOLOGY. 2019: 260–65

  View details for Web of Science ID 000538564000038

• Revisiting complete response in light chain amyloidosis. Leukemia Sidana, S., Dispenzieri, A., Murray, D. L., Go, R. S., Buadi, F. K., Lacy, M. Q., Gonsalves, W. I., Dingli, D., Warsame, R., Kourelis, T., Muchtar, E., Hayman, S. R., Kapoor, P., Kyle, R. A., Leung, N., Rajkumar, S. V., Gertz, M. A., Kumar, S. K. 2019

  View details for DOI 10.1038/s41375-019-0664-9

  View details for PubMedID 31772296

• Bone marrow plasma cells 20% or greater discriminate presentation, response, and survival in AL amyloidosis. Leukemia Muchtar, E., Gertz, M. A., Kourelis, T. V., Sidana, S., Go, R. S., Lacy, M. Q., Buadi, F. K., Dingli, D., Hayman, S. R., Kapoor, P., Leung, N., Fonder, A., Hobbs, M., Lisa Hwa, Y., Gonsalves, W., Warsame, R., Russell, S., Lust, J. A., Lin, Y., Zeldenrust, S., Rajkumar, S. V., Kyle, R. A., Kumar, S. K., Dispenzieri, A. 2019

  Abstract

  We explored the association between bone marrow plasma cells (BMPCs) and disease presentation and outcome among 1574 AL patients. Three BMPC groups were formulated: <5% (n=231, 15% of study population), 5-19% (n=1045, 66%), and ≥20% (n=298, 19%). Heart and renal involvement were more and less prevalent, respectively, with increasing BMPCs. Patients with ≥20% BMPCs had higher likelihood for classic myeloma phenotype with less skewed lambda restriction, a higher rate of intact immunoglobulin secretion, a lower hemoglobin and higher rates of hypercalcemia and bone lytic lesions. High-risk cytogenetic abnormalities were more common in ≥20% BMPCs. Complete hematological response was less frequent with rising BMPCs. The median survival was inversely associated with the BMPC groups (81, 33, 12 months for <5%, 5-19%, and ≥20% BMPCs, respectively; P<0.001). Survival discrimination was maintained at 1-year landmark and in those who achieved a complete response. Multivariate analysis accounting for known prognostic markers yielded an independent prognostic role for ≥20% BMPCs, but not for the other BMPC groups. AL patients with 20% or greater BMPCs have poorer outcome independent of their cardiac risk category and stem cell transplant eligibility. Distinct interventions in these patients should be explored to improve outcome.

  View details for DOI 10.1038/s41375-019-0655-x

  View details for PubMedID 31758090

• Long-Term Outcomes and Organ Responses with Daratumumab Therapy in Previously Treated Patients with AL Amyloidosis Chung, A., Kaufman, G. P., Sidana, S., Eckhert, E., Schrier, S., Arai, S., Lafayette, R., Witteles, R., Liedtke, M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-122152

  View details for Web of Science ID 000577160403100

• Patient Experience of Chimeric Antigen Receptor (CAR)-T Cell Therapy Vs. Stem Cell Transplant: Longitudinal Patient Reported Adverse Events, Cognition and Quality of Life Sidana, S., Thanarajasingam, G., Griffin, J., Thompson, C. A., Burtis, M., Warsame, R., Paludo, J., Cheville, A., Gertz, M. A., Dispenzieri, A., Villasboas, J., Ansell, S. M., Rajkumar, S., Yost, K. J., Bennani, N., Siddiqui, M., Lin, Y., Kumar, S. K., Dueck, A. C. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121715

  View details for Web of Science ID 000518218500863

• Glycosylation of Immunoglobulin Light Chains Is Highly Prevalent in Cold Agglutinin Disease Sidana, S., Murray, D. L., Dasari, S., Go, R. S., Willrich, M., Snyder, M., Kohlhagen, M., Lust, J. A., Muchtar, E., Kourelis, T., Kumar, S. K., Dispenzieri, A., Gertz, M. A. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121712

  View details for Web of Science ID 000577164600090

• Immunoglobulin Variable Gene Region (IGVL) Usage Correlates with Distinct Clinical Presentation in IgM Versus Non-IgM Light Chain Amyloidosis Sidana, S., Dasari, S., Kourelis, T., Dispenzieri, A., Murray, D. L., King, R. L., McPhail, E. D., Ramirez-Alvarado, M., Kumar, S. K., Gertz, M. A. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-121714

  View details for Web of Science ID 000577160403042

• Favorable Long-Term Outcomes after Daratumumab Discontinuation in AL Amyloidosis Patients Achieving Deep Responses Chung, A., Kaufman, G. P., Sidana, S., Iberri, D., Eckhert, E., Schrier, S., Lafayette, R., Arai, S., Witteles, R., Liedtke, M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-124981

  View details for Web of Science ID 000577160403156

• Impact of consolidation therapy post autologous stem cell transplant in patients with light chain amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Al Saleh, A. S., Sidiqi, M., Sidana, S., Muchtar, E., Dispenzieri, A., Dingli, D., Lacy, M. Q., Warsame, R. M., Gonsalves, W. I., Kourelis, T. V., Hogan, W. J., Hayman, S. R., Wolf, R. C., Kapoor, P., Buadi, F. K., Kumar, S. K., Gertz, M. A. 2019: 1066–71

  Abstract

  The role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post-transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression-free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression-free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression-free survival for patients who achieve less than very good partial response.

  View details for DOI 10.1002/ajh.25572

  View details for Web of Science ID 000477399700001

  View details for PubMedID 31273808

• Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Sidiqi, M., Dispenzieri, A., Buadi, F. K., Lacy, M. Q., Muchtar, E., Dingli, D., Haynnan, S. R., Gonsalves, W., Kapoor, P., Leung, N., Warsame, R., Kourelis, T., Wolf, R. C., Hogan, W. J., Kumar, S. K., Gertz, M. A. 2019

  Abstract

  In appropriately selected patients with AL amyloidosis, autologous stem cell transplant (ASCT) is an established treatment modality with excellent outcomes and decreasing transplant related mortality (TRM) over time. We report on 15-year overall survival (OS) in 159 patients undergoing ASCT from 1996 to 2003, with median follow up of 17.1 years. Day 100 TRM was 13.2% (n = 21). The OS of ≥15 years was observed in 30% (47/159) of patients. Patients surviving ≥15 years were younger (53 vs 56 years, P = .02), less likely to have lambda as the involved light chain (62% vs 78%, P = .03) and were less likely to have heart involvement (32% vs 56%, P = .005). Median OS of patients with heart involvement vs not was 4.0 vs 11.1 years, P = .006 and actuarial 15-year OS was 23% vs 43%, respectively. A higher proportion of patients with OS ≥15 years received full-dose melphalan conditioning (81% vs 61%, P = .01), and achieved day 100 complete response (CR) (64% vs 24%, P < .001). Median OS amongst patients who achieved CR vs not was 19.3 vs 5.4 years, P < .001. Heart involvement, receiving full-dose melphalan and achieving CR remained independent predictors of OS. AL amyloidosis and related complications were the cause of death in 52% of patients overall (1-5 years post-transplant: 81%; 5-10 years: 62% and 10-15 years: 55%). These results reinforce the key role of ASCT in AL amyloidosis. With improvements in TRM and more options for relapsed disease, we expect the long-term survival post-transplant to improve significantly in the future.

  View details for DOI 10.1002/ajh.25566

  View details for Web of Science ID 000474995300001

  View details for PubMedID 31254301

• Clinical features, laboratory characteristics and outcomes of patients with renal versus cardiac light chain amyloidosis BRITISH JOURNAL OF HAEMATOLOGY Sidana, S., Tandon, N., Gertz, M. A., Dispenzieri, A., Ramirez-Alvarado, M., Murray, D. L., Kourelis, T. V., Buadi, F. K., Kapoor, P., Gonsalves, W., Warsame, R., Lacy, M. Q., Kyle, R. A., Rajkumar, S., Kumar, S. K., Leung, N. 2019; 185 (4): 701–7

  Abstract

  This study evaluated the differences in clinical features of 1077 newly diagnosed AL amyloidosis patients with renal involvement (n = 229, 21%), both cardiac and renal involvement (n = 443, 41%) and cardiac involvement (n = 405, 38%). Significant differences in dFLC (difference in involved and uninvolved light chains) were noted (renal, both, cardiac median: 83, 234 and 349 mg/l, P < 0.001). The proportion of patients with ≥ 10% bone marrow plasma cells (BMPCs) was lowest in renal only patients: 44%, 57%, 64%, respectively, P < 0.001. In a multivariate linear regression model incorporating organ involvement type and BMPCs ≥10%, organ involvement was a significant predictor of dFLC (P < 0.001). Median overall survival (OS) across the three groups was 83 vs. 19 vs. 16 months (P < 0.001) in patients not undergoing transplant and 5-year OS in patients undergoing transplant was 90% vs. 75% vs. 64% (P = 0.007), respectively. In conclusion, renal involvement alone or renal + cardiac involvement in AL amyloidosis is associated with lower circulating light chain burden, which cannot be fully explained by BMPC burden alone. Increased sensitivity of the kidney to light chains, given significant interactions with the renal tubular system and secretion of modified light chain products may play a role in pathogenesis of renal AL amyloidosis and warrants further investigation.

  View details for DOI 10.1111/bjh.15832

  View details for Web of Science ID 000467276100009

  View details for PubMedID 30836444

• Patient-Reported Outcomes with Chimeric Antigen Receptor T Cell Therapy: Challenges and Opportunities. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Chakraborty, R., Sidana, S., Shah, G. L., Scordo, M., Hamilton, B. K., Majhail, N. S. 2019; 25 (5): e155–e162

  Abstract

  Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.

  View details for DOI 10.1016/j.bbmt.2018.11.025

  View details for PubMedID 30500439

• Tetraploidy is associated with poor prognosis at diagnosis in multiple myeloma AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Jevremovic, D., Ketterling, R. P., Tandon, N., Greipp, P. T., Baughn, L. B., Dispenzieri, A., Gertz, M. A., Rajkumar, S., Kumar, S. K. 2019; 94 (5): E117–E120

  View details for DOI 10.1002/ajh.25420

  View details for Web of Science ID 000468303900016

  View details for PubMedID 30680770

• Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Jevremovic, D., Ketterling, R. P., Tandon, N., Dispenzieri, A., Gertz, M. A., Greipp, P. T., Baughn, L. B., Buadi, F. K., Lacy, M. Q., Morice, W., Hanson, C., Timm, M., Dingli, D., Haynnan, S. R., Gonsalves, W., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Rajkumar, S., Kumar, S. K. 2019; 94 (4): 424–30

  Abstract

  Trisomies of odd numbered chromosomes are seen in nearly half of patients with multiple myeloma (MM) and typically correlate with a hyperdiploid state and better overall survival (OS). We compared DNA ploidy of monoclonal plasma cells (as a surrogate for the presence of trisomies) assessed simultaneously by PCPRO (plasma cell proliferative index), a novel method that estimates DNA index by multi-parametric flow cytometry to fluorescence in situ hybridization (FISH) in 1703 patients with plasma cell disorders. The distribution of ploidy was hyperdiploid: 759 (45%), diploid 765 (45%), hypodiploid: 71 (4%), tetraploid/near-tetraploid: 108 (6%). FISH identified trisomies in 82% (621/756) of patients with hyperdiploidy by PCPRO and no trisomy by FISH was observed in 88% (730/834) of patients without hyperdiploidy. 95% (795/834) of patients without hyperdiploidy on PCPRO had one or less trisomy by FISH. Sensitivity and specificity of PCPRO for detecting hyperdiploidy was 86% (621/725) and 84% (730/865), respectively. Sensitivity increased to 94% (579/618) for patients with more than one trisomy. Newly diagnosed MM patients with hyperdiploidy on PCPRO (147/275) had better OS compared to nonhyperdiploid patients (median not reached vs 59 months, P = 0.008) and better progression free survival (median: 33 vs 23 months, P = 0.03). Within the hyperdiploidy group, patients with high-hyperdiploidy (DNA index: 1.19-1.50) versus those with low-hyperdiploidy (DNA index: 1.05-1.18) had superior OS (3 year OS of 88% vs 68% P = 0.03). Ploidy assessment by flow cytometry can provide rapid, valuable prognostic information and also reduces the number of copy number FISH probes required and hence the cost of FISH.

  View details for DOI 10.1002/ajh.25391

  View details for Web of Science ID 000460663200018

  View details for PubMedID 30592078

• Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma BLOOD ADVANCES Tandon, N., Sidana, S., Rajkumar, S., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Kapoor, P., Gonsalves, W., Dispenzieri, A., Kourelis, T., Warsame, R., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Hwa, Y., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Kumar, S. K. 2019; 3 (5): 744–50

  Abstract

  We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and

  View details for DOI 10.1182/bloodadvances.2018022806

  View details for Web of Science ID 000460943400007

  View details for PubMedID 30824418

  View details for PubMedCentralID PMC6418495

• Prognostic Significance of Holter Monitor Findings in Patients With Light Chain Amyloidosis MAYO CLINIC PROCEEDINGS Sidana, S., Tandon, N., Brady, P. A., Grogan, M., Gertz, M. A., Dispenzieri, A., Lin, G., Dingli, D., Buadi, F. K., Lacy, M. Q., Kapoor, P., Gonsalves, W., Muchtar, E., Warsame, R., Kumar, S. K., Kourelis, T. 2019; 94 (3): 455–64

  Abstract

  To evaluate the prognostic impact of Holter findings in patients with light chain amyloidosis.We evaluated 239 patients in whom light chain amyloidosis was diagnosed from January 1, 2010, through December 31, 2015, who underwent 24-hour Holter monitoring.Holter testing was done before stem cell transplant evaluation in 183 of the 239 patients (76.6%) and at diagnosis in 50 (20.9%). Holter findings were nonsustained ventricular tachycardia (NSVT) in 60 patients (25.1%), ventricular couplets in 103 (43.1)%, accelerated idioventricular rhythm in 32 (13.4%), and atrial fibrillation (AF) in 18 (7.5%). Overall survival (OS) at 3 and 6 months after Holter monitoring in patients with AF vs without AF was 78% (95% CI, 54%-91%) vs 96% (95% CI, 92%-98%) (P=.002) and 61% (95% CI, 38%-80%) vs 92% (95% CI, 87%-95%), (P<.001), respectively. In patients with and without NSVT, 3- and 6-month OS after Holter testing was 90% (95% CI, 80%-94%) vs 96% (95% CI, 91%-98%) (P=.12) and 77% (95% CI, 64%-85%) vs 94% (95% CI, 89%-97%) (P<.001), respectively. For patients with and without ventricular couplets, 3- and 6-month OS was 94% (95% CI, 88%-97%) vs 94% (95% CI, 89%-97%) (P=.98) and 84% (95% CI, 75%-89%) vs 94% (95% CI, 89%-97%) (P=.01), respectively. Atrial fibrillation (hazard ratio, 2.5; 95% CI, 1.2-5.0; P=.02) and NSVT (hazard ratio, 2.0; 95% CI, 1.1-3.5; P=.02) were independent predictors for OS after accounting for age and Mayo stage. For patients undergoing routine testing before stem cell transplant, AF (P=.002) and NSVT (P=.02) were associated with inferior OS at 6 months but did not retain statistical significance after adjusting for Mayo stage (P=.10 and P=.54, respectively).Atrial fibrillation and NSVT on 24-hour Holter monitoring are associated with inferior short-term OS outcomes but do not impact peritransplant mortality.

  View details for DOI 10.1016/j.mayocp.2018.08.039

  View details for Web of Science ID 000460059600018

  View details for PubMedID 30718070

• Primary systemic amyloidosis in patients with Waldenstrom macroglobulinemia LEUKEMIA Zanwar, S., Abeykoon, J. P., Ansell, S. M., Gertz, M. A., Dispenzieri, A., Muchtar, E., Sidana, S., Tandon, N., Rajkumar, S., Dingli, D., Go, R., Lacy, M. Q., Kourelis, T., Witzig, T. E., Inwards, D., Buadi, F., Gonsalves, W., Habermann, T., Johnston, P., Nowakowski, G., Kyle, R. A., Kumar, S., Kapoor, P. 2019; 33 (3): 790–94

  View details for DOI 10.1038/s41375-018-0286-7

  View details for Web of Science ID 000460406600024

  View details for PubMedID 30315235

• Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Warsame, R. M., Kourelis, T., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Rajkumar, S., Kumar, S. K. 2019; 33 (3): 730–38

  Abstract

  Achieving a complete response (CR) is associated with improved overall survival (OS) in multiple myeloma (MM), but data on duration of CR (DurCR) are limited. We evaluated 351 patients (2004-2016), achieving CR with first-line therapy. Patients with sustained DurCR ≥ 24 months (n = 177) had better OS; 150 vs. 81 months, p < 0.001. DurCR ≥ 24 months remained a significant predictor for OS (HR: 0.3, 95% CI: 0.2-0.5, p < 0.001) after adjusting for age, revised ISS stage, transplant and maintenance therapy. Landmark analysis at 24 months demonstrated similar results, OS: 150 vs. 83 months, p < 0.001. Survival benefit persisted even after loss of CR, with median OS being 89 vs. 56 months (p = 0.005), respectively. Patterns of loss of CR were heterogeneous, with biochemical relapse in 59 (25%); symptomatic relapse in 58 (24%); positive immunofixation/monoclonal protein rise not meeting relapse/progression criteria in 88 (37%) and abnormal free light chain ratio in LC MM in 34 (14%) patients. OS from start of first-line therapy was superior in patients starting second-line treatment for biochemical vs. symptomatic relapse (125 vs. 81 months, p = 0.001). This is likely attributable to underlying disease biology and prevention of end-organ damage by early treatment initiation, as benefit was independent of R-ISS stage.

  View details for DOI 10.1038/s41375-018-0271-1

  View details for Web of Science ID 000460406600015

  View details for PubMedID 30323358

• A case of ibrutinib-associated aspergillosis presenting with central nervous system, myocardial, pulmonary, intramuscular, and subcutaneous abscesses LEUKEMIA & LYMPHOMA McCarter, S. J., Vijayvargiya, P., Sidana, S., Nault, A. M., Lane, C. E., Lehman, J. S., Wilson, J. W., Parikh, S. A., Nowakowski, G. S., Al-Kali, A. 2019; 60 (2): 559–61

  View details for DOI 10.1080/10428194.2018.1494271

  View details for Web of Science ID 000463555600047

  View details for PubMedID 30070153

• IgM AL amyloidosis: delineating disease biology and outcomes with clinical, genomic and bone marrow morphological features. Leukemia Sidana, S. n., Larson, D. P., Greipp, P. T., He, R. n., McPhail, E. D., Dispenzieri, A. n., Murray, D. L., Dasari, S. n., Ansell, S. M., Muchtar, E. n., Gonsalves, W. I., Kourelis, T. V., Ramirez-Alvarado, M. n., Kapoor, P. n., Rajkumar, S. V., Lacy, M. Q., Buadi, F. K., Leung, N. n., Kyle, R. A., Kumar, S. K., King, R. L., Gertz, M. A. 2019

  Abstract

  This study evaluates newly diagnosed IgM (6%, n = 75/1174) vs. non-IgM light chain amyloidosis patients. IgM amyloid patients had lower light chains (12.5 vs. 22.5 mg/dL; p < 0.001). Heart (56% vs. 73%, p = 0.002) and >1 organ involvement (31% vs. 44%, p = 0.02) was less common in IgM amyloidosis, while soft tissue and peripheral nerve involvement was more common. t(11;14) was less common (27% vs. 50%, p = 0.008) in IgM amyloidosis. Rates of MYD88L265P and CXCR4WHIM mutation in IgM amyloidosis were 58% (29/50) and 17% (8/46). Diagnosis after hematopathology review in IgM amyloidosis was pure plasma cell neoplasm (PPCN) in 23% (16/70), lymphoplasmacytic neoplasm (LPL) in 63% (44/70) patients, and other (14%). LPL vs. PPCN groups had distinct genetic abnormalities: t(11;14): 0% (0/18) vs. 60% (9/15), p < 0.001; MYD88L265P mutation: 84% (27/32) vs. 0% (0/14), p < 0.001; CXCR4 mutation: 29% (8/28) vs. 0% (0/14), p = 0.04. Overall survival was shorter in IgM AL when stratified by Mayo 2012 stage; stage 1/2 (59 vs. 125.9 months, p = 0.003) and stage 3/4 (6.5 vs. 12.9 months, p = 0.075), likely due to lower hematologic response rates (6 months: 39% vs. 59%, p = 0.008). We characterized two subtypes of IgM amyloidosis (LPL/PPCN). This can aid in therapeutic decision-making, with treatment directed at the clonal disease.

  View details for DOI 10.1038/s41375-019-0667-6

  View details for PubMedID 31780812

• Evidence-Based Minireview: Does achieving MRD negativity after initial therapy improve prognosis for high-risk myeloma patients? Hematology. American Society of Hematology. Education Program Sidana, S. n., Manasanch, E. n. 2019; 2019 (1): 142–47

  Abstract

  You are evaluating a 47-year-old man with revised international staging system stage III myeloma who recently underwent an autologous stem cell transplant after receiving 6 cycles of carfilzomib, lenalidomide, and dexamethasone for newly diagnosed disease. Fluorescence in situ hybridization testing at initial presentation also revealed t(4;14). On day 100 evaluation after transplant, he has achieved a stringent complete response. Two-tube, 8-color advanced flow cytometry with a sensitivity of 10-5 shows no minimal residual disease. Whole-body positron emission tomography/computed tomography scan shows resolution of all fluorodeoxyglucose avid uptake seen at diagnosis. The patient asks you how these test results impact his prognosis and whether this overcomes his baseline high risk from t(4;14)?

  View details for DOI 10.1182/hematology.2019000075

  View details for PubMedID 31808853

• CAR T-cell therapy: is it prime time in myeloma? Hematology. American Society of Hematology. Education Program Sidana, S. n., Shah, N. n. 2019; 2019 (1): 260–65

  Abstract

  Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.

  View details for DOI 10.1182/hematology.2019000370

  View details for PubMedID 31808895

• CAR T-cell therapy: is it prime time in myeloma? Blood advances Sidana, S. n., Shah, N. n. 2019; 3 (21): 3473–80

  Abstract

  Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.

  View details for DOI 10.1182/bloodadvances.2019000370

  View details for PubMedID 31714964

• Should we measure clonal circulating plasma cells in light chain amyloidosis? Oncotarget Sidana, S., Kumar, S. K., Gonsalves, W. I. 2018; 9 (86): 35607–8

  View details for DOI 10.18632/oncotarget.26289

  View details for PubMedID 30479690

• 59-Year-Old Man With Fatigue, Weight Loss, and Hepatomegaly MAYO CLINIC PROCEEDINGS Orme, J. J., Sidana, S., Gonsalves, W. I. 2018; 93 (10): 1525–29

  View details for DOI 10.1016/j.mayocp.2017.12.028

  View details for Web of Science ID 000446070100023

  View details for PubMedID 30104045

• Reply to A. Piccardo et al, E. Hindie et al, MC Kreissl et al, M. Doss, J. Buscombe, R. Fisher, M. Sollini et al, M. Lichtenstein, and M. Tulchinsky et al JOURNAL OF CLINICAL ONCOLOGY Molenaar, R. J., Sidana, S., Radivoyevitch, T., Gerds, A. T., Carraway, H. E., Kalaycio, M., Nazha, A., Adelstein, D. J., Nasr, C., Maciejewski, J. P., Majhail, N. S., Sekeres, M. A., Mukherjee, S. 2018; 36 (18): 1889-+

  View details for DOI 10.1200/JCO.2018.78.4074

  View details for Web of Science ID 000439452300025

  View details for PubMedID 29723096

• Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer JOURNAL OF CLINICAL ONCOLOGY Molenaar, R. J., Sidana, S., Radivoyevitch, T., Advani, A. S., Gerds, A. T., Carraway, H. E., Angelini, D., Kalaycio, M., Nazha, A., Adelstein, D. J., Nasr, C., Maciejewski, J. P., Majhail, N. S., Sekeres, M. A., Mukherjee, S. 2018; 36 (18): 1831-+

  Abstract

  Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

  View details for DOI 10.1200/JCO.2017.75.0232

  View details for Web of Science ID 000439452300010

  View details for PubMedID 29252123

• Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Dingli, D., Jevremovic, D., Morice, W. G., Kapoor, P., Kourelis, T. V., Lacy, M. Q., Hayman, S. R., Buadi, F. K., Leung, N., Go, R. S., Lin, Y., Russell, S. J., Lust, J. A., Zeldenrust, S. R., Warsame, R., Hwa, Y. L., Hobbs, M., Fonder, A., Kyle, R. A., Rajkumar, S., Kumar, S. K., Gonsalves, W. I. 2018; 32 (6): 1421–26

  Abstract

  We evaluated the prognostic impact of clonal circulating plasma cells (cPCs) detected by six-color multi-parametric flow cytometry (MFC) in light chain (AL) amyloidosis at diagnosis. Of the 154 patients who underwent MFC, cPCs were detected in 42% (n = 65) patients. Median number of cPCs was 81 per 150,000 events (range: 6-17,844). High bone marrow plasma cell percentage was an independent predictor of presence of cPCs. Presence of cPCs at diagnosis was associated with inferior overall survival (OS) (90 vs. 98 months, p = 0.003) and inferior progression free survival (PFS) (31 vs. 52 months, p = 0.02). Estimated 1, 2 and 5 year OS in the two groups was: 74, 64 and 57 and 89, 87, and 80%, respectively. Estimated PFS at 1, 2, and 5 years was: 69, 56, and 23% and 80, 74, and 37%, respectively. Furthermore, the presence of cPCs at diagnosis was an independent adverse predictor of OS in multivariable analysis. Achieving a very-good partial response, or better, was able to overcome the adverse impact of cPCs at diagnosis. Patients with cPCs at diagnosis may warrant closer monitoring post-treatment, especially if they do not achieve a deep hematologic response.

  View details for DOI 10.1038/s41375-018-0063-7

  View details for Web of Science ID 000434474100015

  View details for PubMedID 29483709

  View details for PubMedCentralID PMC5992020

• The importance of bone marrow examination in patients with light chain amyloidosis achieving a complete response LEUKEMIA Sidana, S., Tandon, N., Dispenzieri, A., Gertz, M. A., Rajkumar, S., Kumar, S. K. 2018; 32 (5): 1243–46

  View details for DOI 10.1038/s41375-018-0022-3

  View details for Web of Science ID 000431769800020

  View details for PubMedID 29568089

• Impact of prior melphalan exposure on stem cell collection in light chain amyloidosis BONE MARROW TRANSPLANTATION Sidana, S., Tandon, N., Gertz, M. A., Dispenzieri, A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S., Hogan, W. J., Kumar, S. K. 2018; 53 (3): 326–33

  Abstract

  Use of melphalan in multiple myeloma was observed to have a deleterious effect on stem cell collection in older studies. There is limited data on the impact of melphalan in light chain (AL) amyloidosis, especially in the plerixafor era. We retrospectively evaluated stem cell mobilization in 610 patients with AL amyloidosis, of which 79 had prior exposure to melphalan, 167 to other chemotherapeutics, while 364 had no chemotherapy exposure. Collection of CD34+ stem cells × 106/kg was lower in the melphalan group. Median total yields in the melphalan, non-melphalan, and no chemotherapy groups were 5.5, 7.7, and 7.8, respectively; p < 0.001. Day-1 yields were 2.7, 3.5, and 4.0 (p = 0.0003), respectively, and median yields per collection were 2.0, 3.3, and 4.0 (p < 0.001), respectively. Similar results were observed in the sub-group analysis after plerixafor was integrated in our collection algorithm (2009). Patients in the melphalan group had higher failure rate of 9% vs. 2% each in the other two groups (p = 0.006). Impact of melphalan was dose-dependent, with cumulative melphalan exposure of >150 mg (median: three cycles) resulting in lower yields. Therefore, duration of melphalan exposure prior to stem cell collection should be limited, ideally, not exceeding more than two cycles of treatment.

  View details for DOI 10.1038/s41409-017-0020-5

  View details for Web of Science ID 000427675200011

  View details for PubMedID 29269795

• Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains. Leukemia Sidana, S. n., Tandon, N. n., Dispenzieri, A. n., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Dingli, D. n., Fonder, A. L., Hayman, S. R., Hobbs, M. A., Gonsalves, W. I., Hwa, Y. L., Kapoor, P. n., Kyle, R. A., Leung, N. n., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S. V., Kumar, S. K. 2018; 32 (3): 729–35

  Abstract

  Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.

  View details for DOI 10.1038/leu.2017.286

  View details for PubMedID 28919633

• Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL) AMERICAN JOURNAL OF HEMATOLOGY Tandon, N., Sidana, S., Dispenzieri, A., Gertz, M. A., Lacy, M. Q., Dingli, D., Buadi, F. K., Fonder, A. L., Hayman, S. R., Hwa, Y., Hobbs, M. A., Kapoor, P., Gonsalves, W. I., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Kyle, R. A., Rajkumar, S., Kumar, S. K. 2018; 93 (1): 17–22

  Abstract

  Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

  View details for DOI 10.1002/ajh.24919

  View details for Web of Science ID 000417527300011

  View details for PubMedID 28960427

• Risk of developing chronic myeloid neoplasms in well-differentiated thyroid cancer patients treated with radioactive iodine. Leukemia Molenaar, R. J., Pleyer, C. n., Radivoyevitch, T. n., Sidana, S. n., Godley, A. n., Advani, A. S., Gerds, A. T., Carraway, H. E., Kalaycio, M. n., Nazha, A. n., Adelstein, D. J., Nasr, C. n., Angelini, D. n., Maciejewski, J. P., Majhail, N. n., Sekeres, M. A., Mukherjee, S. n. 2018; 32 (4): 952–59

  Abstract

  Exposure to ionizing radiation increases the risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but such risks are not known in well-differentiated thyroid cancer (WDTC) patients treated with radioactive iodine (RAI). A total of 148 215 WDTC patients were identified from Surveillance, Epidemiology and End Results registries between 1973 and 2014, of whom 54% underwent definitive thyroidectomy and 46% received adjuvant RAI. With a median follow-up of 6.6 years, 77 and 66 WDTC patients developed MDS and MPN, respectively. Excess absolute risks for MDS and MPN from RAI treatment when compared to background rates in the US population were 6.6 and 8.1 cases per 100 000 person-years, respectively. Compared to background population rates, relative risks of developing MDS (3.85 (95% confidence interval, 1.7-7.6); P=0.0005) and MPN (3.13 (1.1-6.8); P=0.012) were significantly elevated in the second and third year following adjuvant RAI therapy, but not after thyroidectomy alone. The increased risk was significantly associated with WDTC size ⩾2 cm or regional disease. Development of MDS was associated with shorter median overall survival in WDTC survivors (10.3 vs 22.5 years; P<0.001). These data suggest that RAI treatment for WDTC is associated with increased risk of MDS with short latency and poor survival.

  View details for DOI 10.1038/leu.2017.323

  View details for PubMedID 29104287

• Clinical presentation and outcomes of patients with type 1 monoclonal cryoglobulinemia AMERICAN JOURNAL OF HEMATOLOGY Sidana, S., Rajkumar, S., Dispenzieri, A., Lacy, M. Q., Gertz, M. A., Buadi, F. K., Hayman, S. R., Dingli, D., Kapoor, P., Gonsalves, W. I., Go, R. S., Hwa, Y., Leung, N., Fonder, A. L., Hobbs, M. A., Zeldenrust, S. R., Russell, S. J., Lust, J. A., Kyle, R. A., Kumar, S. K. 2017; 92 (7): 668–73

  Abstract

  We describe a series of 102 patients diagnosed from January 1, 1990 to December 31, 2015 with Type 1 monoclonal cryoglobulinemia (MoC). Symptoms were seen in 89 (87%) patients, including: cutaneous symptoms in 64 (63%) patients, with purpura (n = 43, 42%) and ulcers/gangrene (n = 35, 34%) being most common; neurological findings in 33 (32%) patients, most frequently sensory neuropathy (n = 24, 24%); vasomotor symptoms, mainly Raynaud's phenomenon in 25 (25%); arthralgias in 24 (24%); and renal manifestations, primarily glomerulonephritis in 14 (14%) patients. An underlying lymphoproliferative disorder was identified in 94 (92%) subjects; MGUS-39, myeloma-20, lymphoplasmacytic lymphoma-21 and others-14. Treatment was initiated in 73 (72%) patients, primarily for cryoglobulinemia-related symptoms in 57. Treatment regimens consisted of: steroids ± alkylating agents in 29 (40%), novel myeloma therapies in 16 (22%), rituximab with alkylating agents in 12 (16%) and rituximab ± steroids in 11 (15%) patients; 22 patients received plasmapheresis. Six patients underwent autologous stem cell transplant. Cryocrit at treatment initiation, change in cryocrit and time to nadir cryocrit were predictive of symptom improvement. Treatment directed toward the underlying clonal disorder resulted in improvement (n = 47) or stabilization (n = 16) of symptoms in the majority of patients and disappearance of cryoglobulin in over one-half.

  View details for DOI 10.1002/ajh.24745

  View details for Web of Science ID 000405194900016

  View details for PubMedID 28370486

  View details for PubMedCentralID PMC5579826

• Treatment patterns and outcome following initial relapse or refractory disease in patients with systemic light chain amyloidosis AMERICAN JOURNAL OF HEMATOLOGY Tandon, N., Sidana, S., Gertz, M. A., Dispenzieri, A., Lacy, M. Q., Buadi, F. K., Dingli, D., Fonder, A. L., Hobbs, M. A., Hayman, S. R., Gonsalves, W. I., Hwa, Y., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Rajkumar, S., Kumar, S. K. 2017; 92 (6): 549–54

  Abstract

  We analyzed the outcomes following initial relapse or refractory disease in systemic light chain amyloidosis (AL) and the impact of type of therapy employed.A total of 1327 patients with AL seen at Mayo Clinic within 90 days of diagnosis, between 2006 and 2015, were reviewed. The study included 366 patients experiencing a documented hematological or organ relapse or refractory disease requiring start of second line therapy. Overall survival (OS) and time to next treatment (TTNT) were calculated from start of second line treatment.The median time to require second line treatment was 16.2 months (1-93) from the start of first line therapy. At relapse, patients received proteasome inhibitors (PI; 45.1%), immunomodulators (IMiD; 22.7%), alkylators (9%), PI and IMiD combination (4.1%), autologous transplant (3.8%), steroids and other therapies (4.9%). Among these, 124 (33.9%) required change or reinstitution of therapy. The median time to require third line treatment was 31 months (95% CI; 24, 40.5) and the median overall survival (OS) was 38.8 months (95% CI; 29.6, 52.6) from the start of second line treatment. Retreatment with same therapy at relapse significantly reduced TTNT (22 m vs 32.3 m; P = .01) as compared to different therapy; but did not have any impact OS (30.8 m vs 51.1 m; P = .5). In conclusion, this study provides important information about outcomes of patients with AL who require second line treatment for relapsed/refractory disease . Treatment with a different therapy at relapse improves time to next therapy but does not impact OS.

  View details for DOI 10.1002/ajh.24723

  View details for Web of Science ID 000400932700029

  View details for PubMedID 28314084

• Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival. Bone marrow transplantation Tandon, N. n., Muchtar, E. n., Sidana, S. n., Dispenzieri, A. n., Lacy, M. Q., Dingli, D. n., Buadi, F. K., Hayman, S. R., Chakraborty, R. n., Hogan, W. J., Gonsalves, W. n., Warsame, R. n., Kourelis, T. V., Leung, N. n., Kapoor, P. n., Kumar, S. K., Gertz, M. A. 2017; 52 (8): 1126–32

  Abstract

  Autologous stem cell transplantation (ASCT) is an important treatment modality in light chain (AL) amyloidosis. Use of reduced-dose melphalan conditioning is common, given the associated organ and functional decline. The impact of full-intensity melphalan conditioning (n=314) was compared to reduced-dose conditioning (n=143). Patients in the full-intensity group were younger, with better performance status, fewer involved organs, lower tumor burden and lower Mayo stage. Full-dose conditioning was associated with higher rate of very good partial response or better (79% vs 62%; P<0.001), complete response rate (53% vs 37%; P=0.003) and organ response rate (74% vs 59%; P=0.002) as compared to reduced-dose conditioning. PFS was superior in the full-intensity group compared to the reduced-dose group (4-year PFS 55% vs 31%; P<0.001) as well as a longer overall survival (OS) 4-year OS (86% vs 54%; P<0.001). In addition, the OS and PFS were significantly lower in the reduced-dose group compared to the full-intensity group in Mayo stage III/IV as well as stage I/II. A multivariate analysis confirmed an independent impact for conditioning dose on PFS/OS. This study calls for re-assessment of the use of reduced-dose conditioning in ASCT for AL amyloidosis.

  View details for DOI 10.1038/bmt.2017.68

  View details for PubMedID 28394369

• Predictors of early treatment failure following initial therapy for systemic immunoglobulin light-chain amyloidosis AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS Tandon, N., Sidana, S., Rajkumar, S., Dispenzieri, A., Gertz, M. A., Lacy, M. Q., Kyle, R. A., Buadi, F. K., Dingli, D., Hayman, S. R., Fonder, A. L., Hobbs, M. A., Gonsalves, W. I., Kapoor, P., Hwa, Y., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Kumar, S. K. 2017; 24 (3): 183–88

  Abstract

  We analysed factors predicting early treatment failure (ETF), after first-line therapy for light-chain amyloidosis (AL). AL amyloidosis patients seen at Mayo Clinic within 90 days of diagnosis, from 2006 to 2015, excluding those who died within 3 months of initial therapy, were analysed retrospectively. ETF was defined as progression requiring treatment change or death within 12 (ETF12) or 24 (ETF24) months of first-line treatment. Non-ETF included those with a follow-up of more than 12 or 24 months who had progression beyond 12 or 24 months. A total of 724 patients met the study criteria; 244 (33.7%) had ETF12 and 388 (53.6%) had ETF24. Patients with ETF12 were older (64.1 vs. 62.2 years) with higher prevalence of cardiac (81 vs. 64.1%) and multi-organ involvement (67.2 vs. 45.4%) and higher proportion of patients with t(11; 14) (58.5 vs. 44.3%) or in higher Mayo 2012 stage (58.5 vs. 41.1%).The median follow-up was 5.4 years from start of initial therapy. In multivariate analysis, presence of t(11; 14) and non-incorporation of autologous transplant in initial therapy are significant predictors of ETF12 (p = .01and p = .003) and ETF24 (p = .0001 and p = .005) while Mayo stage is predictive of ETF24 (p = .002), but not ETF12.

  View details for DOI 10.1080/13506129.2017.1351354

  View details for Web of Science ID 000416629600007

  View details for PubMedID 28699793

• Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis. PloS one Sidana, S. n., Narkhede, M. n., Elson, P. n., Hastings, D. n., Faiman, B. n., Valent, J. n., Samaras, C. n., Hamilton, K. n., Liu, H. K., Smith, M. R., Reu, F. J. 2017; 12 (3): e0172996

  Abstract

  Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001).Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

  View details for DOI 10.1371/journal.pone.0172996

  View details for PubMedID 28278302

  View details for PubMedCentralID PMC5344345

• Got zinc? An exfoliative rash in a parenteral nutrition-dependent patient. Journal of general internal medicine Sidana, S. n., Madanat, Y. n., Pile, J. n. 2015; 30 (4): 529–30

  View details for DOI 10.1007/s11606-014-3099-z

  View details for PubMedID 25410883

  View details for PubMedCentralID PMC4370997

• Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer. PloS one Chaturvedi, S. n., Sidana, S. n., Elson, P. n., Khorana, A. A., McCrae, K. R. 2014; 9 (8): e94048

  Abstract

  The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer.Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR).At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29-11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE.Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population.

  View details for DOI 10.1371/journal.pone.0094048

  View details for PubMedID 25126949

  View details for PubMedCentralID PMC4134135

• Prevalence of depression in students of a medical college in New Delhi: A cross-sectional study AUSTRALASIAN MEDICAL JOURNAL Sidana, S., Kishore, J., Ghosh, V., Gulati, D., Jiloha, R. C., Anand, T. 2012; 5 (5): 247–50

  Abstract

  Medical education is associated with various pressures and stresses which can lead to depression. This study was undertaken to discover the prevalence of depression in medical students and various factors contributing to depression.This is a cross-sectional, questionnaire-based study. Using stratified random sampling, 237 students were selected according to year of study. Patient Health Questionnaire (PHQ-9), based on PRIME-MD Today, was used to make a provisional diagnosis of depression.The overall prevalence of provisionally diagnosed depressive and major depressive disorder using PHQ-9 was 21.5% and 7.6%, respectively. Year of study and academic performance of students had a statistically significant association with depression. Other factors, including gender, self-reported past history of depression, family history of psychiatric disorders, type of social support, family structure, number of siblings and education of parents were not found to have any significant association with prevalence of depression in the study. It was also observed that students were reluctant to seek help for depressive symptoms.

  View details for DOI 10.4066/AMJ.2012.750

  View details for Web of Science ID 000218033900001

  View details for PubMedID 22848319

  View details for PubMedCentralID PMC3395288