Impact of the COVID-19 pandemic on treatment approaches of multiple myeloma

Main Article Content

Poy Theprungsirikul, MD Natalia Neparidze, MD


Cancer has been recognized as one of the major comorbidities associated with severe outcomes in the novel coronavirus disease 19 (COVID-19) patients. Compared to those with solid tumors and those without cancer, patients with hematologic malignancies appear to have more severe clinical outcomes and higher rate of mortality from COVID-19. This was particularly demonstrated during the early pandemic period. The COVID-19 pandemic has posed additional challenges in the management of hematologic malignancies, including establishing prompt diagnoses, providing optimal treatment while minimizing the risk and sequela of COVID-19 infection. Given these challenges, clinical practice guidelines and recommendations on management of hematologic malignancies during the COVID-19 pandemic were developed and proposed based on expert panels and individual expert opinions. Multiple myeloma is the second most common hematologic malignancy. The management of patients with multiple myeloma during the COVID-19 pandemic is extremely challenging as patients with multiple myeloma are particularly vulnerable to infections due to underlying humoral and cellular immune dysfunction, cytotoxic chemotherapy, immunotherapy, cellular therapy and steroid regimens, advanced age, and the presence of other comorbidities. In this paper, we attempt to provide a general review of clinical practice management patterns during and after the COVID-19 pandemic in patients with multiple myeloma and demonstrate how changes evolved as more knowledge was gained over time. Specifically, we review the impact of the pandemic on treatment approaches, supportive care, and vaccinations for patients with newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, patients with stable disease, and those with precursor states like monoclonal gammopathy and smoldering multiple myeloma. During early pandemic several changes were noted in myeloma care including minor delay in time to treatment initiation and tendency to defer autologous stem cell transplant. However, after 2022, with the advent of effective vaccines and treatment strategies the severity of COVID-19 infection decreased and care of myeloma returned to usual management, incorporating transplant, CART and multiple novel immune therapy approaches. Finally, we highlight the importance of meticulous vaccination schedule for patients with myeloma for all common viral, bacterial pathogens and vaccination against COVID-19.

Keywords: COVID-19, COVID-19 pandemic, Impact of the COVID-19 pandemic, treatment approaches, myeloma

Article Details

How to Cite
THEPRUNGSIRIKUL, Poy; NEPARIDZE, Natalia. Impact of the COVID-19 pandemic on treatment approaches of multiple myeloma. Medical Research Archives, [S.l.], v. 11, n. 6, june 2023. ISSN 2375-1924. Available at: <>. Date accessed: 24 feb. 2024. doi:
Review Articles


1. World Health Organization (WHO). WHO coronavirus (COVID-19) dashboard. Updated February 28, 2023. Accessed February 28, 2023.

2. Richards M, Anderson M, Carter P, Ebert BL, Mossialos E. The impact of the COVID-19 pandemic on cancer care. Nat Cancer. 2020;1 (6):565-567. doi:10.1038/s43018-020-0074-y

3. El-Sharkawi D, Iyengar S. Haematological cancers and the risk of severe COVID-19: exploration and critical evaluation of the evidence to date. Br J Haematol. 2020;190(3):336-345. doi:10.1111/bjh.16956

4. Erdal GS, Polat O, Erdem GU, et al. The mortality rate of COVID-19 was high in cancer patients: a retrospective single-center study. Int J Clin Oncol. 2021;26(5):826-834. doi:10.1007/s10147-021-01863-6

5. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020;21(3):335-337. doi:10.1016/S1470-2045(20)30096-6

6. Meng Y, Lu W, Guo E, et al. Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis. J Hematol Oncol. 2020;13(1):75. doi:10.1186/s13045-020-00907-0

7. Saini KS, Tagliamento M, Lambertini M, et al. Mortality in patients with cancer and coronavirus disease 2019: a systematic review and pooled analysis of 52 studies. Eur J Cancer. 2020;139:43-50. doi:10.1016/j.ejca.2020.08.011

8. He W, Chen L, Chen L, et al. COVID-19 in persons with haematological cancers. Leukemia. 2020;34(6):1637-1645. doi:10.1038/s41375-020-0836-7

9. Langerbeins P, Hallek M. COVID-19 in patients with hematologic malignancy. Blood. 2022; 140(3):236-252. doi: 10.1182/blood.2021012251

10. Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004;351:1860-1873. doi:10.1056/NEJMra041875

11. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046-1060. doi:10.1056/NEJMra1011442

12. van de Donk NWCJ, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397(10272): 410-427. doi:10.1016/S0140-6736(21)00135-5

13. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086-1107. doi:10.1002/ajh.26590

14. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. doi:10.3322/caac.21708

15. Hultcrantz M, Richter J, Rosenbaum CA, et al. COVID-19 infections and clinical outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers. Blood Cancer Discov. 2020;1(3):234-243. doi:10.1158/2643-3230.BCD-20-0102

16. Al Saleh AS, Sher T, Gertz MA. Multiple myeloma in the time of COVID-19. Acta Haematol. 2020;143(5):410-416. doi:10.1159/000507690

17. Martínez-López J, Mateos MV, Encinas C, et al. Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality. Blood Cancer J. 2020;10(10):103. doi:10.1038/s41408-020-00372-5

18. Chari A, Samur MK, Martinez-Lopez J, et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood. 2020;136(26):3033-3040. doi:10.1182/blood.2020008150

19. Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma. J Clin Oncol. 2022; 40(25):2901-2912. doi:10.1200/JCO.21.01935

20. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288

21. Mateos MV, Martínez BP, González-Calle V. High-risk multiple myeloma: how to treat at diagnosis and relapse? Hematology Am Soc Hematol Educ Program. 2021;2021(1):30-36. doi:10.1182/hematology.2021000229

22. Terpos E, Engelhardt M, Cook G, et al. Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia. 2020;34(8):2000-2011. doi:10.1038/s41375-020-0876-z

23. Hungria V, Garnica M, Crusoé EQ, et al. Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe. Hematol Transfus Cell Ther. 2020;42(3):200-205. doi:10.1016/j.htct.2020.05.001

24. Jethava YS, Fonseca R, Landgren O. Management of multiple myeloma during COVID-19 pandemic. Leuk Res Rep. 2020;14:100212. doi:10.1016/j.lrr.2020.100212

25. Malard F, Mohty M. Management of patients with multiple myeloma during the COVID-19 pandemic. Lancet Haematol. 2020 Jun;7(6):e435-e437. doi:10.1016/S2352-3026(20)30124-1

26. Jimenez-Zepeda VH, Yau P, Stewart D, et al. Impact of COVID-19 on the diagnosis and management of multiple myeloma: experience from a Canadian center. Rev Invest Clin. 2022;74(1):16-22. doi:10.24875/RIC.21000347

27. Neparidze N, Wang R, Zeidan AM, et al. Changes in multiple myeloma treatment patterns during the early COVID-19 pandemic period. Leukemia. 2022;36(8):2136-2139. doi:10.1038/s41375-022-01633-x

28. Richter J, Ailawadhi S, Lee HC, et al. Impact of COVID-19 on treatment patterns and management of multiple myeloma: insights from the Connect® MM Registry. Blood. 2022;140:8089-91. doi:10.1182/blood-2022-158627

29. Shah D, McAuliff K, Pittos E, et al. COVID-19 impact on multiple myeloma prescribing patterns. J Clin Oncol. 2022;40(28_suppl):123. doi:10.1200/JCO.2022.40.28_suppl.123

30. Buske C, Dreyling M, Alvarez-Larrán A, et al. Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA interdisciplinary expert consensus. ESMO Open. 2022;7(2):100403. doi:10.1016/j.esmoop.2022.100403

31. Moreau P. How I treat myeloma with new agents. Blood. 2017;130(13):1507-1513. doi:10.1182/blood-2017-05-743203

32. van de Donk NWCJ, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood. 2018; 131(1):13-29. doi:10.1182/blood-2017-06-740944

33. Wang Y, Sanchez L, Siegel DS, Wang ML. Elotuzumab for the treatment of multiple myeloma. J Hematol Oncol. 2016;9(1):55. doi:10.1186/s13045-016-0284-z

34. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0

35. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021; 384(8):705-716. doi:10.1056/NEJMoa2024850

36. Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2023;41(6):1265-1274. doi:10.1200/JCO.22.00842

37. Mailankody S, Devlin SM, Landa J, et al. GPRC5D-targeted CAR T cells for myeloma. N Engl J Med. 2022;387(13):1196-1206. doi:10.1056/NEJMoa2209900

38. Stewart AK, Krishnan AY, Singhal S, et al. Phase I study of the anti-FcRH5 antibody-drug conjugate DFRF4539A in relapsed or refractory multiple myeloma. Blood Cancer J. 2019;9(2):17. doi:10.1038/s41408-019-0178-8

39. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022; 387(6):495-505. doi:10.1056/NEJMoa2203478

40. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366(19):1782-91. doi: 10.1056/NEJMoa1114138

41. Holstein SA, Jung SH, Richardson PG, et al. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. Lancet Haematol. 2017;4(9):e431-e442. doi:10.1016/S2352-3026(17)30140-0

42. Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20(1):57-73. doi:10.1016/S1470-2045(18)30687-9

43. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012; 366(19):1770-81. doi:10.1056/NEJMoa1114083

44. McCarthy PL, Holstein SA, Petrucci MT, et al. Lenalidomide maintenance after autologous stem-cell transplantation in newly diagnosed multiple myeloma: a meta-analysis. J Clin Oncol. 2017;35(29):3279-3289. doi:10.1200/JCO.2017.72.6679

45. Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895-905. doi:10.1056/NEJMoa1402888

46. Benboubker L, Dimopoulos MA, Dispenzieri A, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371(10):906-17. doi:10.1056/NEJMoa1402551

47. Facon T, Dimopoulos MA, Dispenzieri A, et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 2018;131(3):301-310. doi:10.1182/blood-2017-07-795047

48. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6

49. Lakshman A, Rajkumar SV, Buadi FK, et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J. 2018; 8(6):59. doi:10.1038/s41408-018-0077-4

50. Mateos MV, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020; 10(10):102. doi:10.1038/s41408-020-00366-3

51. Visram A, Cook J, Warsame R. Smoldering multiple myeloma: evolving diagnostic criteria and treatment strategies. Hematology Am Soc Hematol Educ Program. 2021;2021(1): 673-681. doi:10.1182/hematology.2021000304

52. Turesson I, Bjorkholm M, Blimark CH, Kristinsson S, Velez R, Landgren O. Rapidly changing myeloma epidemiology in the general population: increased incidence, older patients, and longer survival. Eur J Haematol. 2018:10.1111/ejh.13083. doi:10.1111/ejh.13083

53. Miceli TS, Gonsalves WI, Buadi FK. Supportive care in multiple myeloma: current practices and advances. Cancer Treat Res Commun. 2021;29:100476. doi:10.1016/j.ctarc.2021.100476

54. Callander NS, Baljevic M, Adekola K, et al. NCCN guidelines® insights: Multiple myeloma, Version 3.2022. J Natl Compr Canc Netw. 2022;20(1):8-19. doi:10.6004/jnccn.2022.0002

55. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309-322. doi:10.1016/j.annonc.2020.11.014

56. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/JCO.18.02096

57. Terpos E, Zamagni E, Lentzsch S, et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e119-e130. doi:10.1016/S1470-2045(20)30559-3

58. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414-23. doi:10.1038/sj.leu.2405062

59. Maertens J, Cesaro S, Maschmeyer G, et al. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother. 2016;71(9):2397-404. doi:10.1093/jac/dkw157

60. Fukushima T, Sato T, Nakamura T, et al. Daily 500 mg valacyclovir is effective for prevention of Varicella zoster virus reactivation in patients with multiple myeloma treated with bortezomib. Anticancer Res. 2012;32(12):5437-40.

61. Vickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009;115(1):229-32. doi:10.1002/cncr.24006

62. Drgona L, Gudiol C, Lanini S, Salzberger B, Ippolito G, Mikulska M. ESCMID study group for infections in compromised hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4). Clin Microbiol Infect. 2018;24 Suppl 2:S83-S94. doi:10.1016/j.cmi.2018.03.022

63. Hsu P, Lin TW, Gau JP, et al. Risk of early mortality in patients with newly diagnosed multiple myeloma. Medicine (Baltimore). 2015;94(50):e2305. doi:10.1097/MD.0000000000002305

64. Ludwig H, Kumar S. Prevention of infections including vaccination strategies in multiple myeloma. Am J Hematol. 2023;98 Suppl 2:S46-S62. doi:10.1002/ajh.26766

65. Mai EK, Haas EM, Lücke S, et al. A systematic classification of death causes in multiple myeloma. Blood Cancer J. 2018; 8(3):30. doi:10.1038/s41408-018-0068-5

66. Mohty M, Cavo M, Fink L, et al. Understanding mortality in multiple myeloma: findings of a European retrospective chart review. Eur J Haematol. 2019;103(2):107-115. doi:10.1111/ejh.13264

67. Ludwig H, Boccadoro M, Moreau P, et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2021;35(1):31-44. doi:10.1038/s41375-020-01016-0

68. Ludwig H, Sonneveld P, Facon T, et al. COVID-19 vaccination in patients with multiple myeloma: a consensus of the European Myeloma Network. Lancet Haematol. 2021;8(12):e934-e946. doi:10.1016/S2352-3026(21)00278-7

69. Pagano L, Salmanton-García J, Marchesi F, et al. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association survey (EPICOVIDEHA). J Hematol Oncol. 2021;14(1):168. doi:10.1186/s13045-021-01177-0

70. International Myeloma Society. Recommendations for anti-COVID-19 vaccination in patients with multiple myeloma (MM) and related conditions, AL amyloidosis and other monoclonal gammopathies of clinical significance. Accessed February 28, 2023.

71. American Society of Hematology (ASH). General principles of COVID-19 vaccines for immunocompromised patients. Updated April 14, 2022. Accessed February 28, 2023.

72. American Society of Hematology (ASH). ASH-ASTCT COVID-19 vaccination for HCT and CAR T cell recipients: frequently asked questions. Updated March 22, 2022. Accessed February 28, 2023.