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Predictive Factors for Early Relapse in Multiple Myeloma after Autologous Hematopoietic Stem Cell Transplant



 

Andrew Mayer Pourmoussa, MD1; Ricardo Spielberger, MD2; Jilian Cai, MD2;
Odelia Khoshbin, OMS3; Leonardo Farol, MD2; Thai Cao, MD2; Firoozeh Sahebi, MD2

Perm J 2019;23:19.012 [Full Citation]

https://doi.org/10.7812/TPP/19.012
E-pub: 10/11/2019

ABSTRACT

Introduction: Despite advances in therapy for multiple myeloma, patients have continued to experience relapse. We sought to better understand this.
Objective: To identify factors that predict early relapse in patients with multiple myeloma who receive autologous hematopoietic peripheral stem cell transplant (HSCT).
Methods: Retrospective analysis of Kaiser Permanente Southern California patients who received HSCTs between 2008 and 2012.
Results: A total of 141 patients were included. Factors found to be associated with inferior progression-free survival were disease status less than complete response at the time of HSCT, no use of maintenance therapy after HSCT, International Staging System stage III, and high Freiburg Comorbidity Index. Disease status less than complete response, stage III, higher Freiburg Comorbidity Index, no use of maintenance therapy, and male sex were the most predictive factors for early relapse (< 18 months).
Discussion: Our results identified a subgroup of high-risk individuals with multiple myeloma who will continue to do poorly after HSCT with the best available treatment using a combination of proteasome inhibitors and immunomodulatory drugs. These results highlight the need for consideration of alternative therapy in such instances.

INTRODUCTION

Multiple myeloma is a neoplastic proliferation of plasma cells accounting for 10% of hematologic malignancies.1 Rapid advances in the understanding of genetics and biology of the disease have led to the introduction of new targeted therapeutic agents and clinically significant improvements in disease outcome.2,3 An induction regimen using a combination of immunomodulatory drugs, proteasome inhibitors, and dexamethasone followed by autologous hematopoietic stem cell transplant (HSCT) is considered standard treatment of newly diagnosed multiple myeloma in physically fit patients.4-8 The superiority of high-dose chemotherapy and autologous HSCT was initially shown in comparison to conventional chemotherapeutic agents.9,10 More recently, in the era of targeted therapies, several randomized clinical trials have confirmed improved progression-free survival (PFS)11-13 and overall survival (OS)11 in favor of a combination of new targeted therapies and early autologous HSCT. The beneficial role of maintenance treatment after autologous HSCT has also been examined in randomized clinical trials, supporting its use in this setting.14,15 Despite these advances, patients continue to experience relapse. Factors such as lack of response, stage, and high-risk cytogenetics have been linked to poor outcome.1,16-18 Scoring systems that consider additional factors such as age, comorbidities, and cognitive/physical conditions have been described in helping to predict survival.19,20

We examined PFS and OS in patients who received induction therapy using immunomodulatory drugs and/or proteasome inhibitor-based regimens followed by autologous stem cell transplant between 2008 and 2012. The objective of this study was to investigate prognostic factors that correlate with early relapse using the best available treatment in the modern era of new targeted agents, reflecting real-world practice. The electronic medical records were available for all patients, allowing for evaluation of all preexisting comorbidities and all health-related issues outside the transplant center—data that may not always be captured.

METHODS

The study was approved by the institutional review board of Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA. Patients with multiple myeloma who were treated at Kaiser Permanente Southern California medical centers and received autologous HSCT between January 1, 2008, and January 1, 2012, were identified for chart review electronically through International Classification of Diseases, Ninth Revision (ICD-9) codes for multiple myeloma (203.0) and multiple myeloma post HSCT (41.0X). This chart review was carried out via an integrated electronic system (Epic, Epic Systems, Verona, WI), which allows access to patient medical records outside the transplant referral center. Protected health information was used in conducting our research in accordance with the Health Insurance Portability and Accountability Act (HIPAA).

All patients underwent induction therapy using combinations of immunomodulatory drugs, proteasome inhibitors, and dexamethasone followed by autologous HSCT. Data on age, sex, International Staging System (ISS) stage, type of induction therapy, bone marrow cytogenetics and/or fluorescence in situ hybridization (FISH) abnormalities, disease status at the time of HSCT, and use of maintenance therapy were collected (Tables 1 and 2). High-risk cytogenetic abnormalities were defined by the presence of at least 1 of the following: del(17p), t(4;14), t(14;16), t(14;20), del(1p), and hypoploidy. The Freiberg Comorbidity Index (FCI) was evaluated as well. The FCI is a simple assessment that is used to determine risk relating to comorbidities in multiple myeloma. This index takes into account performance status, renal impairment, and lung disease. In this 0- to 3-point total scale, individual points are assigned for Karnofsky Performance Status less than or equal to 70% vs greater than 70%, a glomerular filtration rate less than 30 mL/min/1.73 m2 vs greater than 30 mL/min/1.73 m2, and the presence of moderate to severe lung disease vs absence of or mild disease.21 Compared with other comorbidity indexes, such as the Charlson Comorbidity Index, Hematopoietic Cell Transplantation-specific Comorbidity Index, Kaplan-Feinstein Index, and Satariano Index, the FCI has been reported to better stratify risk in patients with multiple myeloma.22 

Statistical Analysis

We performed statistical analysis to study the following variables at the time of transplant: Age, sex, ISS classification, FCI, Karnofsky Performance Status, disease status, along with cytogenetics/FISH results, use of posttransplant maintenance therapy, best response after transplant, time to progression, time to last contact, and cause of death related to multiple myeloma. We also computed censoring variables for use in the Cox proportional hazards models in studying our main outcomes of interest: Time to progression in PFS, OS, and relapse in less than 18 months (early relapse). Each of these variables was included in a single-variable proportional hazards model of each outcome. A Kaplan-Meier survival analysis was also done with each corresponding proportional hazards regression for each single variable and the 3 outcomes. Confidence intervals (CIs) for the survival probabilities were calculated using the log transformation. Although the results were similar between these 2 analyses, the software-displayed output (SAS version 9.3, SAS Institute, Cary, NC) was different, which allowed checking different assumptions about the variables. These variables were collected together in main effects, multivariate Cox proportional hazards regression models, 1 for each of the outcomes. The multivariate models were run with hierarchical stepwise selection and also backward elimination with terms being retained at the 0.10 level. In addition, we ran a multivariate logistic regression of PFS less than 18 months vs at least 18 months using main effects with stepwise selection and backward elimination, retaining variables significant at the 0.10 level. Main effects were focused because of an inability to credibly examine interactions stemming from a relatively low sample size.

19.012

RESULTS

A total of 141 patients were identified for our study. Patient characteristics are shown in Table 1. The median follow-up for the study group was 63.9 months (range = 6.2-103.3 months). Patients’ median age was 58 years (range = 30-70 years). Seventy-five patients were men and 66 were women. The median Karnofsky Performance Status was 90% (range = 60%-100%), and the median FCI was 0 (range = 0-2). The median time from diagnosis to HSCT was 7.4 months (range = 3.7- 93.2 months). Forty-five patients (31.9%) had ISS stage I disease, 52 (36.9%) had ISS stage II, and 44 (31.2%) had ISS stage III. Twenty-four (17%) patients were in complete response at the time of the transplant, 116 patients (82.3%) had a partial response, and 1 patient (0.7%) had no response. Ninety-three (66%) had standard-risk cytogenetics/FISH findings and 48 (34%) had high-risk findings. One hundred two patients (72.3%) received maintenance therapy after transplant. The practice for posttransplant maintenance therapy changed over the study period from primarily thalidomide (13 patients, 12.8%) to lenalidomide (74 patients, 72.6%). Fifteen patients received bortezomib alone or in combination with immunomodulatory drugs (14.7%) as maintenance therapy (Table 2).

Thirty-eight patients (27%) experienced early time to disease progression less than 18 months from the time of transplant. Variable summaries for early vs late time to progression groups are shown in Table 3. The patient characteristics were balanced between the 2 groups except for lower proportion of ISS stage III, lower FCI, higher likelihood of receiving complete response, and receiving maintenance therapy in those with late relapse. Four-year PFS for the whole group was 41.8% (95% CI = 34.4% to 50.8%), and the OS was 81.5% (95% CI = 75.4% to 88.2%; Figures 1 and 2). The OS for the early relapse/progression group during the 4-year study period was 44.7% (95% CI = 31.4% to 63.7%; Figure 3). The median PFS for the whole group was 37 months (95% CI = 29-47 months), with a median PFS of 8.6 months (95% CI = 6.9 to 10.7 months) for those with early relapse/progression vs 62 months (95% CI = 47 months to absence of relapse) for those who did not experience relapse. The median PFS for patients receiving maintenance therapy was 47 months (95% CI = 34-67 months) vs 24 months (95% CI = 14-30 months) for those without maintenance therapy.

The median OS for the whole group was 109 months (95% CI = 94-151 months), with a median OS of 31.4 months for those with early relapse/progression (95% CI = 22.2-56 months) vs 115 months (95% CI = 109-151 months) for those who did not progress before 18 months.

In the Cox proportional hazards model, built using backward elimination for PFS using continuous age at diagnosis, the factors associated with increased PFS were maintenance therapy (p < 0.0001), complete response at the time of HSCT (p = 0.004), lower ISS (p = 0.005), and lower FCI (p = 0.024). Using age at diagnosis dichotomized younger than age 65 years at the time of HSCT, the factors associated with increased PFS were maintenance therapy (p < 0.0001), complete response at the time of HSCT (p = 0.003), lower ISS stage (p = 0.010), lower FCI (p = 0.014), and younger age (p = 0.043).

In the final Cox proportional hazards model, built using backward elimination for OS using continuous age at diagnosis, the factors associated with increased OS were lower FCI (p = 0.019) and lower ISS stage (p = 0.066). With use of age at diagnosis dichotomized at less than 65 years vs 65 years or more, the factors associated with increases OS were lower FCI (p = 0.016), younger age (p = 0.093), and lower ISS stage (p = 0.099).

Factors associated with early relapse (< 18 months) were examined with logistic regression built using backward elimination. Using continuous age at diagnosis, the factors associated with early relapse/progression were higher FCI (p = 0.024), no use of maintenance therapy (p = 0.032), less than complete response at the time of HSCT (p = 0.063), and male sex (p = 0.064). The model was unchanged when we used age at diagnosis dichotomized at younger than age 65 years vs older than age 65 years.

DISCUSSION

Despite significant improvement in the outcomes of patients with multiple myeloma, relapse remains the main cause of treatment failure. Determination of patients destined for early progression is of particular importance in selecting those who are expected to have a poor outcome with best available treatment using a combination of proteasome inhibitors, immunomodulatory drugs, and autologous stem cell transplant.

Traditionally, patients receive a few cycles of induction therapy followed by stem cell transplant. The results of our study suggest that the achievement of complete response before transplant may help to prevent early relapse or progression of the disease. This is in accordance with prior observations where achievement of complete response or very good partial response before autologous stem cell transplant translated to better long-term outcomes.23,24 Therefore, efforts to achieve a deep cytoreduction and preferably complete response, which may be attainable with newer, more effective targeted agents and monoclonal antibodies, should be explored as a means to improve outcomes in future prospective trials. Indeed, achievement of a negative minimal residual state is the subject of ongoing studies.25 

Limitations of our study included broader categorization of pretransplant disease status as complete response vs less than complete response because of difficult extraction of very good partial response vs partial response status from medical records during the chart review process. We did not find any association between high-risk cytogenetics/FISH findings and early relapse. This may be related to the small number of patients with poor cytogenetics results. We did observe a statistically significant correlation between higher FCI and early relapse and progression. The FCI has shown a strong clinical relevance for OS and PFS in patients with multiple myeloma. To our knowledge, this is the first report that has shown a high FCI to predict early relapse/progression. This requires further examination to determine if the presence of other comorbidities promotes a permissive microenvironment for tumor growth.

In a study by the Mayo Clinic consisting of 511 patients, the authors reported serum albumin level below 3.5 g/dL and high-risk FISH results to be predictive of early relapse.26 A recent report by the Center for International Blood and Marrow Transplant Research group reported that the proportion of patients with early relapse was stable over time, at 35% to 38%.27 Similarly, this group reported a higher cancer stage, unresponsiveness to chemotherapy, and no use of post-HSCT maintenance therapy associated with early relapse.27 Novel monoclonal antibodies daratumumab, isatuximab, and elotuzumab alone or in combination with other new targeted agents have been shown to have significant activity in relapsed refractory multiple myeloma.28-34 Our results, however, have identified a subgroup of high-risk patients who will continue to do poorly with the best available treatment and should be included in clinical trials investigating new therapeutic strategies such as novel monoclonal antibodies daratumumab, isatuximab, and elotuzumab. Indeed, ongoing clinical trials are examining the addition of these monoclonal antibodies as induction or consolidation therapy before and after HSCT.35 Other immune-modulating approaches such as vaccination and T-cell therapy (CAR T-cell, bispecific T-cell engagers, also called BiTE monoclonal antibodies)36 are also under investigation and hold promise for a better cytoreduction and long-term disease control for high-risk patients.

Conclusion

We conducted this retrospective analysis to identify the risk factors predictive of early relapse despite best available treatment. In our study, the risk factors identified were disease status of less than complete response at the time of HSCT, no use of maintenance therapy after HSCT, ISS stage III, and high FCI. We also examined factors predictive of early relapse within 18 months of transplant. Disease status less than complete response, ISS stage III, no use of maintenance therapy, and male sex were the most predictive for early relapse, supporting the need for better disease control prior to transplant.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.

Acknowledgments

Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

We would like to thank the clinical research support staff at Kaiser Permanente Los Angeles Medical Center, CA, for assistance with facilitating our study.

How to Cite this Article

Pourmoussa AM, Spielberger R, Cai J, et al. Predictive factors for early relapse in multiple myeloma after autologous hematopoietic stem cell transplant. Perm J 2019;23:19.012. DOI: https://doi.org/10.7812/TPP/19.012

Author Affiliations

1 Department of Internal Medicine, Los Angeles Medical Center, CA

2 Bone Marrow Transplant Department, Los Angeles Medical Center, CA

3 College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA

Corresponding Author

Andrew Mayer Pourmoussa, MD (andrew.pourmoussa@kp.org)

References
1. McKenna RW, Kuehl WM, Grogan TM, Harris NL, Coupland RW. Plasma cell neoplasms. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: International Agency for Research on Cancer; 2008. p 200-13.
 2. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia 2014 May;28(5):1122-8. DOI: https://doi.org/10.1038/leu.2013.313.
 3. Pulte D, Gondos A, Brenner H. Improvement in survival of older adults with multiple myeloma: Results of an updated period analysis of SEER data. Oncologist 2011 Oct;16(11):1600-3. DOI: https://doi.org/10.1634/theoncologist.2011-0229.
 4. Rajkumar SV, Jacobus S, Callander NS,et al; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: An open-label randomised controlled trial. Lancet Oncol 2010 Jan;11(1):29-37. DOI: https://doi​.org/10.1016/S1470-2045(09)70284-0.
 5. Cavo M, Tacchetti P, Patriarca F, et al; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: A randomised phase 3 study. Lancet 2010 Dec 18;376(9758):2075-85. DOI: https://doi​.org/10.1016/S0140-6736(10)61424-9.
 6. Harousseau JL, Attal M, Avet-Loiseau H, et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: Results of the IFM 2005-01 phase III trial. J Clin Oncol 2010 Oct 20;28(30):4621-9. DOI: https://doi.org/10.1200/JCO.2009.27.9158.
 7. San Miguel JF, Schlag R, Khuageva NK, et al; VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008 Aug 28;359:906-17. DOI: https://doi.org/10.1056/NEJMoa0801479.
 8. Kumar SK, Callandar NS, Alsina M, et al. Multiple myeloma, version 3.2017, NCCN clinical practice guidelines in oncology. JNCCN 2017 Feb;15(2):230-69. DOI: https://​doi.org/10.6004/jnccn.2017.0023.
 9. Attal M, Harousseau J-L, Stoppa A-M, et al; Intergroupe Français du Myélome. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996 Jul 11;335(2):91-7. DOI: https://doi.org/10.1056/NEJM199607113350204.
 10. Child JA, Morgan GJ, Davies FE, et al; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003 May 8;348(19):1875-83. DOI: https://doi.org/10​.1056/NEJMoa022340.
 11. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 2014 Sep 4;371(10):895-905. DOI: https://doi.org/10.1056/NEJMoa1402888.
 12. Gay F, Oliva S, Petrucci MT, et al. Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial. Lancet Oncol 2015 Dec;16(16):1617-29. DOI: https://doi​.org/10.1016/S1470-2045(15)00389-7.
 13. Attal M, Lauwers-Cances V, Hulin C, et al; IFM 2009 Study. Lenalidomide, bortezomib and dexamethasone with transplantation for myeloma. N Engl J Med 2017 Apr 6;376(14):1311-20. DOI: https://doi.org/10.1056/NEJMoa1611750.
 14. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for myeloma. N Engl J Med 2012 May 10;366(19):1770-81. DOI: https://doi.org/10.1056/NEJMoa1114083.
 15. Attal M, Lauwers-Cances V, Marit G, et al; IFM Investigators. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Eng J Med 2012 May 10;366(19):1782-91. DOI: https://doi.org/10.1056/NEJMoa1114138.
 16. Chng WJ, Gertz MA, Chung TH, et al. Correlation between array-comparative genomic hybridization-defined genomic gains and losses and survival: Identification of 1p31-32 deletion as a prognostic factor in myeloma. Leukemia 2010 Apr;24(4):833-42. DOI: https://doi.org/10.1038/leu.2010.21.
 17. Neben K, Lokhorst HM, Jauch A, et al. Administration of bortezomib before and after autologous stem cell transplantation improves outcome in multiple myeloma patients with deletion 17p. Blood 2012 Jan 26;119(4):940-8. DOI: https://doi.org/10.1182/blood​-2011-09-379164.
 18. Gertz MA, Lacy MQ, Dispenzieri A, et al. Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3; q32), and -17p13 in myeloma patients treated with high-dose therapy. Blood 2005 Oct 15;106(8):2837-40. DOI: https://doi.org/10.1182/blood-2005-04-1411.
 19. Larocca A, Bringhen S, Evangelista A, et al. A simple score, based on geriatric assessment, improves prediction of survival, and risk of serious adverse events in elderly newly diagnosed multiple myeloma patients [abstract]. Blood 2013;122(21):687.
 20. Saad A, Mahindra A, Zhang MJ, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 2014 Mar;20(3):402-8.e1. DOI: https://doi​.org/10.1016/j.bbmt.2013.12.557.
 21. Kim SM, Kim AJ, Jung HA, et al. Comparison of the Freiburg and Charlson Comorbidity Indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma. Biomed Res Int 2014;2014;437852. DOI: https://doi.org​/10.1155/2014/437852.
 22. Kleber M, Ihorst G, Terhorst M, et al. Comorbidity as a prognostic variable in multiple myeloma: Comparative evaluation of common comorbidity scores and use of a novel MM-comorbidity score. Blood Cancer J 2011 Sep;1(9):e35). DOI: https://doi.org/10.10​38/bcj.2011.34.
 23. Lahuerta JJ, Mateos MV, Martínez-López J, et al. Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: Sequential improvement of response and achievement of complete response are associated with longer survival. J Clin Oncol 2008 Dec 10;26(35):5775-82. DOI: https://doi.org/10.12​00/JCO.2008.17.9721.
 24. Gertz MA, Kumar S, Lacy MQ, et al. Stem cell transplantation in multiple myeloma: Impact of response failure with thalidomide or lenalidomide induction. Blood 2010 Mar 25;115(12):2348-53. DOI: https://doi.org/10.1182/blood-2009-07-235531.
 25. Paiva B, Van Dongen JM, Orfao A. New criteria for response assessment: Role of minimal residual disease in multiple myeloma. Blood Journal 2015 125: 3059-3068. DOI: https://doi.org/10.1182/blood-2014-11-568907.
 26. Majithia N, Rajkumar SV, Lacy MQ, et al. Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents. Leukemia 2016 Nov;30(11):2208-13. DOI: https://doi.org/10.1038/leu.2016.147.
 27. Kumar SK, Dispenzieri A, Fraser R, et al. Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time. Leukemia 2018 Apr;32(4):986-95. DOI: https://doi.org/10.1038/leu.2017.331.
 28. Jelinek T, Koristka M, Cermakova Z, Hajek R. Daratumumab—Hope for myeloma patients, a challenge for clinical laboratories [article in Czech]. Klin Onkol 2017 Winter;30(1):13-9. DOI: https://doi.org/10.14735/amko201713.
 29. Iida S, Suzuki K, Kusumoto S, et al. Safety and efficacy of daratumumab in Japanese patients with relapsed or refractory multiple myeloma: A multicenter, phase 1 dose-escalation study. Int J Hematol 2017 Oct;106(4):541-51. DOI: https://doi.org/10.1007​/s12185-017-2281-6.
 30. Martin T, Baz R, Benson DM, et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood 2017 Jun 22;129(25):3294-303. DOI: https://doi.org/10.1182/blood-2016-09-740787.
 31. Chari A, Suvannasankha A, Fay JW, et al. Daratumumab plus pomalidomide and dexamethasone in relapse and/or refractory multiple myeloma. Blood 2017 Aug 24;130(8):974-81. DOI: https://doi.org/10.1182/blood-2017-05-785246
 32. San-Miguel JF, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial. Lancet Oncol 2014 Oct;15(11):1195-206. DOI: https://doi​.org/10.1016/S1470-2045(14)70440-1.
 33. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015 Jan 8;372(2):142-52. DOI: https://doi.org/10.1056/NEJMoa1411321.
 34. Lonial S, Dimopoulos M, Palumbo A, et al; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med 2015 Aug 13;373(7):621-31. DOI: https://doi.org/10.1056/NEJMoa1505654.
 35. Voorhees PM, Costa LJ, Reeves B. Interim safety analysis of a phase 2 randomized study of daratumumab (Dara), lenalidomide (R), bortezomib (V), and dexamethasone (d; Dara-Rvd) vs Rvd in Patients (pts) with newly diagnosed multiple myeloma (MM) eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). Blood 2017;130(Suppl 1):1879.
 36. Giralt S, Garderet L, Durie B, et al. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma. Biol Blood Marrow Transplant 2015 Dec;21(12):2039-51. DOI: https://doi.org/10.1016/j.bbmt.2015.09.016.

Keywords: bone marrow transplant, blood, hematology and oncology, multiple myeloma

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