How I treat relapsed and/or refractory multiple myeloma

  • Hans C. Lee | The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, United States.
  • Claudio Cerchione Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy.


The expanding therapeutic landscape of relapsed and/or refractory multiple myeloma (RRMM) has contributed to significant improvements in patient outcomes. These have included combinations of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), histone deacetylase inhibitors, and/or alkylating agents. More recently, the approval of the first-in-class nuclear export inhibitor selinexor and the first-in-class B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) belantamab mafodotin has helped address the current unmet need in patients refractory to PI, IMiD, and anti-CD38 mAb directed therapy, otherwise known as triple class refractory myeloma. With the growing number of treatment options in the RRMM therapeutic landscape, the choice and sequencing of drugs and combinations has become increasingly complex. In this review we discuss our approach and considerations in the treatment of both early and late RRRM based on best available data and our clinical experience.



PlumX Metrics


Download data is not yet available.


Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375(8):754-66. DOI:

Spencer A, Lentzsch S, Weisel K, Avet-Loiseau H, Mark TM, Spicka I, et al. Daratumumab plus bortezomib and dexamethasone. Haematologica. 2018;103(12):2079-87. DOI:

Usmani SZ, Quach H, Mateos M-V, Landgren O, Leleu X, Siegel DS, et al. Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM): Primary Analysis Results from the Randomized, Open-Label, Phase 3 Study Candor (NCT03158688). Blood. 2019;134(Supplement_2):LBA-6-LBA-. DOI:

Moreau PD, Meletios Mikhael, Joseph Yong, Kwee Captra, Marcelo Facon, Thierry Hajek, Roman Spicka, Ivan Risse, Marie-Laure Asset, Gaelle Macé, Sandrine Martin, Thomas. Isatuximab Plus Carfilzomib and

Dexamethasone vs Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple

Myeloma (IKEMA): Interim Analysis of A Phase 3 Randomized, Open-Label Study, LB2603. 25th Congress of the

European Hematology

Association. 2020.

Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130(8):974-81. DOI:

Siegel DS, Schiller GJ, Samaras C, Sebag M, Berdeja J, Ganguly S, et al. Pomalidomide, dexamethasone, and daratumumab in relapsed refractory multiple myeloma after lenalidomide treatment. Leukemia. 2020. DOI:

Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373(7):621-31. DOI:

Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621-34. DOI:

Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-52. DOI:

Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;375(14):1319-31. DOI:

Dimopoulos MA, Lonial S, White D, Moreau P, Weisel K, San-Miguel J, et al. Elotuzumab, lenalidomide, and dexamethasone in RRMM: final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J. 2020;10(9):91. DOI:

Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, et al. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2018;36(8):728-34. DOI:

Kaufman JL, Usmani SZ, San-Miguel J, Bahlis N, White DJ, Benboubker L, et al. Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM). Blood. 2019;134(Supplement_1):1866-. DOI:

Bringhen S, Petrucci MT, Larocca A, Conticello C, Rossi D, Magarotto V, et al. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood. 2014;124(1):63-9. DOI:

Kaufman JL, Mina R, Jakubowiak AJ, Zimmerman TL, Wolf JJ, Lewis C, et al. Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study. Blood Cancer J. 2019;9(1):3. DOI:

Costa LJ, Stadtmauer EA, Morgan G, Monohan G, Kovacsovics T, Burwick N, et al. Phase 2 Study of Venetoclax Plus Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Blood. 2018;132(Supplement 1):303-. DOI:

Moreau P, Harrison S, Cavo M, De La Rubia J, Popat R, Gasparetto C, et al. Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma. Blood. 2019;134(Supplement_1):1888-. DOI:

Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122(14):2331-7. DOI:

Manasanch EE, Shah JJ, Lee HC, Weber DM, Thomas SK, Amini B, et al. Phase I/Ib study of carfilzomib and panobinostat with or without dexamethasone in patients with relapsed/refractory multiple myeloma. Haematologica. 2020;105(5):e242-e5. DOI:

Hoylman E, Brown A, Perissinotti AJ, Marini BL, Pianko M, Ye JC, et al. Optimal sequence of daratumumab and elotuzumab in relapsed and refractory multiple myeloma. Leuk Lymphoma. 2020;61(3):691-8. DOI:

Casneuf T, Xu XS, Adams HC, Axel AE, Chiu C, Khan I, et al. Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma. Blood Adv. 2017;1(23):2105-14. DOI:

Gerrie AS, Mikhael JR, Cheng L, Jiang H, Kukreti V, Panzarella T, et al. D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma. Br J Haematol. 2013;161(6):802-10. DOI:

Tabchi S, Nair R, Kunacheewa C, Patel KK, Lee HC, Thomas SK, et al. Retrospective Review of the Use of High-Dose Cyclophosphamide, Bortezomib, Doxorubicin, and Dexamethasone for the Treatment of Multiple Myeloma and Plasma Cell Leukemia. Clin Lymphoma Myeloma Leuk. 2019;19(9):560-9. DOI:

Park S, Lee SJ, Jung CW, Jang JH, Kim SJ, Kim WS, et al. DCEP for relapsed or refractory multiple myeloma after therapy with novel agents. Ann Hematol. 2014;93(1):99-105. DOI:

Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120(14):2817-25. DOI:

Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551-60. DOI:

Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA, et al. Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med. 2019;381(8):727-38. DOI:

Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Pivotal DREAMM-2 study: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs). Journal of Clinical Oncology. 2020;38(15_suppl):8536-. DOI:

Mikhael J, Noonan KR, Faiman B, Gleason C, Nooka AK, Costa LJ, et al. Consensus Recommendations for the Clinical Management of Patients With Multiple Myeloma Treated With Selinexor. Clin Lymphoma Myeloma Leuk. 2020;20(6):351-7. DOI:

Multiple myeloma; Relapsed; Refractory
  • Abstract views: 1486

  • PDF: 656
  • HTML: 0
How to Cite
Lee, H. C., & Cerchione, C. (2020). How I treat relapsed and/or refractory multiple myeloma. Hematology Reports, 12(s1).