Updates in the Treatment of Multiple Myeloma

Presenter: Shaji K. Kumar

For patients with newly diagnosed multiple myeloma (MM), treatment with 4-drug regimens produce deep responses and should be considered for those with high-risk features. Daratumumab + lenalidomide and dexamethasone is standard treatment for newly diagnosed patients not eligible for autologous stem cell transplantation (ASCT). Although lenalidomide remains standard maintenance therapy, in some instances more intensive regimens can be considered. ASCT is more effective when given up-front rather than delayed, but delaying transplantation until disease progression is acceptable. CAR T-cell therapy can provide durable responses, and 2 agents are now FDA-approved for use in multiple myeloma. Bispecific T-cell engagers are also effective for relapsed myeloma, as is the BCL2 inhibitor venetoclax, especially for patients with t(11;14) disease. An emerging novel class of drugs, the CELMoDs (cereblon E3 ligase modulator), target cereblon.

Many new treatments for multiple myeloma have been FDA approved in the past few years, but their optimal use is still being explored. As patients become refractory to one treatment, and then another, questions remain regarding proper sequencing. Do intensive regimens take the place of transplant? These and other clinical questions were addressed at the NCCN 2022 Annual Conference by Shaji K. Kumar, MD, Consultant, Division of Hematology, and the Mark and Judy Mullins Professor of Hematologic Malignancies, Mayo Clinic Cancer Center, as well as Chair of the NCCN Guidelines Panel for Multiple Myeloma.

“As you all know, the treatment paradigm for multiple myeloma has evolved very rapidly, especially over the past few years with the introduction of many new therapies for newly diagnosed and relapsed disease. Despite this, patients continue to relapse, and we continue to try to improve the treatments we use for patients at the time of diagnosis,” he said.

Advances in Transplant-Eligible, Newly Diagnosed Disease

Recent improvements in induction therapy include the addition of a CD38 antibody to bortezomib/lenalidomide/dexamethasone (VRd). In the phase II GRIFFIN trial, the addition of daratumumab to VRd (Dara-VRd) in the induction and consolidation cycles and to lenalidomide for maintenance produced more and deeper responses.1 After 2 years of maintenance, 64% of the patients who received Dara-VRd were minimal residual disease (MRD)–negative compared with 30% who received VRd, which translated into a 54% reduction in disease progression. Progression-free survival (PFS) curves are now starting to separate, with no differences in overall survival (OS) yet.

“We feel that given the high rates of MRD negativity observed with Dara-VRd, this regimen is definitely one to consider for patients with high-risk multiple myeloma, to obtain an MRD-negative state,” Dr. Kumar said. Dara-VRd, therefore, has been added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Multiple Myeloma as useful in certain circumstances.2

With these effective regimens, can the treatment duration be shortened? This question was tackled by the phase II MASTER trial, which examined discontinuing therapy (ie, daratumumab/carfilzomib/lenalidomide/dexamethasone [Dara-KRd]) based on MRD negativity.3 Under an MRD-guided approach, patients either received more cycles of Dara-KRd as consolidation or they did not. Almost all patients achieved at least a very good partial response (VGPR), and 80% achieved MRD negativity. At 2 years, PFS exceeded 90% in patients with 0 or 1 high-risk feature, and OS essentially reached 100%. However, relapse was still common among patients with ≥2 high-risk features, despite this intensive treatment approach.

To Transplant or Not?

“When disease control is achieved, the next question is whether to proceed to autologous stem cell transplantation [ASCT] or to continue with some form of maintenance,” Dr. Kumar said. To this end, the IFM 2009 trial compared up-front ASCT with additional cycles of VRd, with ASCT available upon relapse.4 Despite a 3-drug induction regimen, ASCT still improved PFS by almost 1 year (median PFS, 47.3 vs 35.0 months for VRd alone; hazard ratio [HR], 0.70; 95% CI, 0.59–0.83; P=.0001), though OS differences were not seen. “This provides a clear message that transplant is an effective therapy as part of initial treatment, but it is reasonable to delay transplant to the time of first relapse if desired,” he commented.

Similarly, the FORTE trial examined KRd induction followed by ASCT and demonstrated prolonged PFS over other carfilzomib-based approaches.5 The IFM 2009 and FORTE trials validated that, in transplant-eligible disease, the preferred induction approach is with a proteasome inhibitor, lenalidomide, and dexamethasone along with early transplant, if possible, he said.

Maintenance Therapy Improves PFS

Maintenance therapy after induction and ASCT has become incorporated into clinical care, because it improves not only PFS but also OS.6,7 For patients with high-risk features, however, outcomes after maintenance remain inferior to those achieved in standard-risk patients. As a result, recent studies have attempted to improve upon single-agent lenalidomide as maintenance therapy.

In the FORTE study, a maintenance regimen of carfilzomib + lenalidomide improved PFS compared with lenalidomide alone among all patient subgroups, including those with high-risk features.5 Similarly, all patient subsets in the CASSIOPEIA trial benefited from 2 years of daratumumab maintenance after bortezomib/thalidomide/dexamethasone.8 Compared with the observation group, for which the median PFS was 46.7 months, for those receiving daratumumab, median PFS was not reached (P<.0001). MRD negativity rates were 47.1% and 58.6%, respectively (P<.0001).

Based on these and other phase II/III trials, Dr. Kumar proposed a risk-adapted approach to managing newly diagnosed myeloma. Under this algorithm, standard-risk patients receive induction with VRd for 4 cycles, and then stem cells are collected and patients either proceed to ASCT (preferred) or receive 4 more cycles of VRd, with ASCT on disease progression. Both approaches involve lenalidomide as maintenance. High-risk patients—those with double- or triple-hit disease, del17p, gain 1q, t(4:14), or t(t:16)—will receive 4 cycles of Dara-VRd, then proceed to ASCT (possibly tandem, in the absence of MRD negativity). Maintenance therapy for these patients is bortezomib and lenalidomide.

Transplant-Ineligible Disease

Patients who are not candidates for ASCT often receive VRd (or RVd) “lite,” in which tolerability is improved through dose modifications. The recent MAIA trial randomly assigned patients to daratumumab/lenalidomide/dexamethasone (Dara-Rd) versus Rd alone.9 At 48 months, the median PFS was not reached for Dara-Rd and was 34.4 months for Rd alone (HR, 0.53; 95% CI, 0.43–0.66; P<.0001). Mortality was reduced by 32% (P=.0013).

“Based on this, for standard-risk patients, we would recommend Dara-Rd, or if that regimen cannot be used, using VRd ‘lite’ with continuous therapy (for 12 months) followed by lenalidomide maintenance until disease progression,” Dr. Kumar said. “For high-risk patients, given that data are limited on Dara-Rd, we prefer to use VRd. Of course, consideration can be given to using the quadruplet combination and to reduce doses if patients are able to tolerate it. And we would strongly consider using a proteasome inhibitor + lenalidomide for maintenance until disease progression. For high-risk patients, the critical thing is to get them to achieve a deep response, preferably MRD negativity.”

Treatment of Relapsed Disease

Patients who are transplant-eligible and those who are transplant-ineligible, however, continue to experience relapse. Today, these patients are often “more remote” from their diagnosis (∼5 years), have been off therapy for a while, and thus are “in better shape” when relapse first occurs, he said.

Dr. Kumar bases treatment on the timing and number of prior relapses, according to the following principles:

  • Duration of initial response defines biology.

  • Triplets (2 active classes + dexamethasone) are preferred over doublets, with ≥1 drug from a no-refractory class.

  • For drug and dose selections, clinicians should consider performance status, age, and comorbidities.

  • Clinicians should also take into account prior and residual toxicities from previous therapies.

  • Patients should be treated to maximum response and maintained on one drug until disease progression or intolerability.

“A key factor in selecting therapy is whether the patient is refractory to lenalidomide,” he said, noting that most patients today receive lenalidomide maintenance. With this in mind, Dr. Kumar proposed a rational approach to first and later relapses (Figure 1). “In essence, for the first 2 to 3 relapses, we have the ability to mix and match 3 different monoclonal antibodies, 3 different proteasome inhibitors, and 2 different immunomodulatory drugs (IMiDs) to create regimens that are non–cross-resistant,” he said.

Figure 1.
Figure 1.

Rational approach to first relapse and later.

Abbreviations: d, dexamethasone; D, daratumumab; E, elotuzumab; I, ixazomib; Isa, isatuximab; K, carfilzomib; Len, lenalidomide; P, pomalidomide; R, lenalidomide; V, bortezomib.

Citation: Journal of the National Comprehensive Cancer Network 20, 5.5; 10.6004/jnccn.2022.5004

Highly Refractory Disease

With multiple lines of treatment possible, a triple class–refractory subset of patients (often those with high-risk genetics) is increasingly being seen. A recent study has shown the median PFS for this group of patients to be 4 months, with an OS of 1 year.10

Treatment options for highly refractory patients include several approved drugs: selinexor, a nuclear transport protein inhibitor; belantamab mafodotin-blmf, an antibody–drug conjugate; and 2 CAR T-cell therapies targeting B-cell maturation antigen (BCMA). Currently in clinical trials are T-cell engagers (ie, bispecific antibodies), CELMoDs (cereblon E3 ligase complex modulating drugs), and venetoclax, a BCL2 inhibitor.

In the phase II BOSTON trial, selinexor + bortezomib/dexamethasone led to a median PFS of 13.9 versus 9.5 months for bortezomib/dexamethasone alone (HR, 0.70; P=.0075).11 Selinexor has also successfully been combined with carfilzomib, pomalidomide, and daratumumab. The NCCN Guidelines list selinexor/carfilzomib/dexamethasone as a new option in early relapse.2

Belantamab mafodotin, an antibody–drug conjugate targeting BCMA, has shown efficacy in the DREAMM2 trial as a single agent,12 and is listed in the NCCN Guidelines as an option for patients with late relapse. “Even though the median PFS was only 3 to 4 months, the duration of response for the 30% or so who responded reached almost 1 year. Efficacy seems comparable across all different subgroups and, most importantly, irrespective of prior therapies.” A downside of belantamab mafodotin is ocular toxicity, which requires frequent eye examinations. Lower dosing and less frequent administration are being evaluated to ameliorate this adverse effect.

CAR T-Cell Therapy and Bispecific Antibodies

One of the most exciting advances in the field of myeloma was the introduction of the first CAR T-cell therapy, idecabtagene vicleucel, followed by ciltacabtagene autoleucel—both of which are now recommended for late relapse.

Idecabtagene vicleucel proved itself in the pivotal KarMMA trial, with an overall response rate of 73% (81% at the highest dose level) and high MRD negativity rates.13 Similarly, in CARTITUDE-1, ciltacabtagene autoleucel elicited ≥VGPRs in 94.9% of patients and stringent complete responses in 82.5%.14 The 2-year PFS was 71.0% (95% CI, 57.6–80.9) (>90% sustained MRD negativity) and the OS rate was 74.0% (95% CI, 61.9–82.7), with medians not reached for either endpoint. “This is a striking improvement compared with what we would have expected from patients who are double-refractory,” Dr. Kumar commented.

Newer agents have not yet made their way into the NCCN Guidelines but look promising. Bispecific T-cell engagers are of particular interest because their use does not require apheresis and T-cell manipulation. Instead, they are composed of an antibody with 2 specificities: CD3 on T cells, and a tumor-associated antigen (this varies among the agents) on the myeloma cell.

Teclistamab, which targets BCMA, is furthest along in development. In the MajesTEC-1 trial, 62.0% of triple class–refractory patients experienced response, with responses deepening over time.15 Of patients who achieved at least a complete response, 41.9% achieved MRD negativity. Talquetamab, which targets GPRC5D, produced ≥VGPRs in approximately 53% of patients and stringent complete responses in approximately 10% of patients in the MonumenTAL-1 trial.16 Finally, cevostamab, which targets FcRH5, has produced responses in 56.7% of patients, which were at least VGPRs in 33.3%.17

“What is striking for these bispecific antibodies is that they are quite effective in patients who have been exposed to 5 or 6 prior lines of therapy and whose disease is triple-class–refractory,” Dr. Kumar noted.

Venetoclax and CELMoDs

Venetoclax seems particularly promising for patients with t(11;14) or BCL2-high disease. The phase III BELLINI trial found that this drug significantly improved PFS overall (HR, 0.58; P=.0003).18 The subgroup analysis found a strong benefit in the t(11;14) group (HR, 0.12; P=.0014) and the BCL2-high group (HR, 0.37; P=.0005). Venetoclax is recommended in the NCCN Guidelines for t(11;14 disease) alone.2

Iberdomide is a potent novel CELMoD being developed as a next-generation IMiD. Recent studies have shown iberdomide to be effective in disease refractory to other IMiDs (lenalidomide, pomalidomide) and to BCMA-targeting agents. In CC-220-MM-001, the overall response rate in combination with dexamethasone was 26.2%, and the disease control rate was 79.4%; after BCMA-targeting therapy, these rates were 25.0% and 75.0%, respectively.19

“Clearly, there are multiple new therapies that we hope will be coming into the clinic in the next few years,” he said.

Supportive Care

The 2022 NCCN Guidelines for Multiple Myeloma have been improved with the addition of recommendations for supportive care management of venous thromboembolism, for which risk is increased in patients receiving multiagent chemotherapy regimens and IMiDs. The management algorithm includes a risk stratification scoring system that allows for the personalization of thromboprophylaxis; for example, in determining whether aspirin alone is sufficient or whether anticoagulation is needed (Figure 2). “I certainly recommend that you use the most recent version of the NCCN Guidelines to find the best approach for your patients,” Dr. Kumar said.

Figure 2.
Figure 2.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Multiple Myeloma: management of venous thromboembolism in multiple myeloma [MYEL-I, 1 OF 3]. Version 4.2022.

© 2022 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN®. To view the most recent and complete version of these NCCN Guidelines, go to NCCN.org.

Citation: Journal of the National Comprehensive Cancer Network 20, 5.5; 10.6004/jnccn.2022.5004

References

  • 1.

    Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab plus lenalidomide, bortezomib, and dexamethasone in patients with transplant-eligible newly diagnosed multiple myeloma: updated analysis of GRIFFIN after 24 months of maintenance [abstract]. Blood 2021;138(Suppl 1):Abstract 79.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Kumar SK, Callander NS, Adekola K, et al. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 4.2022. Accessed February 28, 2022. To view the most recent version, visit NCCN.org

    • Search Google Scholar
    • Export Citation
  • 3.

    Costa LJ, Chhabra S, Callander NS, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone, autologous transplantation and MRD response-adapted consolidation and treatment cessation. Final primary endpoint analysis of the MASTER Trial [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 481.

    • Search Google Scholar
    • Export Citation
  • 4.

    Perrot A, Lauwers-Cances V, Cazaubiel T, et al. Early versus late autologous stem cell transplant in newly diagnosed multiple myeloma: long-term follow-up analysis of the IFM 2009 trial [abstract]. Blood 2020;136(Suppl 1):Abstract 39.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Gay F, Musto P, Rota-Scalabrini D, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomized, open-label, phase 2 trial. Lancet Oncol 2021;2:17051720.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;10;366:17701781.

  • 7.

    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;35:32793289.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol 2021;22:13781390.

    • Search Google Scholar
    • Export Citation
  • 9.

    Facon T, Kumar SK, Plesner T, et al. Overall survival results with daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study [abstract]. European Hematology Association 2021 Virtual Congress; June 4–17, 2021. Abstract LB1901.

    • Search Google Scholar
    • Export Citation
  • 10.

    Zanwar S, Ho M, Kapoor P, et al. Outcomes of triple class (proteasome inhibitor, IMiDs and monoclonal antibody) refractory patients with multiple myeloma. Leukemia 2022;36:873876.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomized, open-label, phase 3 trial. Lancet 2020;396:15631573.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    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;21:207221.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021;384:705716.

  • 14.

    Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 549.

    • Search Google Scholar
    • Export Citation
  • 15.

    Moreau P, Usmani SZ, Garfall A, et al. Updated results from MajesTEC-1: phase 1/2 study of teclistamab, a B-cell maturation antigen x CD3 bispecific antibody in relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 896.

    • Search Google Scholar
    • Export Citation
  • 16.

    Krishnan A, Minnema MC, Berdeja JG, et al. Updated phase 1 results from MonumenTAL-1: first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 158.

    • Search Google Scholar
    • Export Citation
  • 17.

    Trudel S, Cohen AD, Krishnan AY, et al. Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pretreated relapsed/refractory multiple myeloma: updated results from an ongoing phase I study [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 157.

    • Search Google Scholar
    • Export Citation
  • 18.

    Kumar SK, Harrison SJ, Cavo M, et al. Final overall survival results from BELLINI, a phase 3 study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma [abstract]. Blood 2021;138(Suppl 1):Abstract 84.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Lonial S, Popat R, Hulin C, et al. Iberdomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma: results from, the dose-expansion phase of the CC-220-MM-001 trial [abstract]. Blood 2021;138(Suppl 1):Abstract 162.

    • Crossref
    • Search Google Scholar
    • Export Citation

Disclosures: Dr. Kumar has disclosed serving as a scientific advisor for and receiving grant/research support from AbbVie, Inc. Amgen Inc., Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica Products, LP, Karyopharm Therapeutics, Regeneron Pharmaceuticals, Inc., Roche Laboratories, Inc., sanofi-aventis U.S., and Takeda Pharmaceuticals North America, Inc.; and receiving honoraria from BeiGene.

Correspondence: Shaji K. Kumar, MD, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Email: kumar.shaji@mayo.edu
  • View in gallery

    Rational approach to first relapse and later.

    Abbreviations: d, dexamethasone; D, daratumumab; E, elotuzumab; I, ixazomib; Isa, isatuximab; K, carfilzomib; Len, lenalidomide; P, pomalidomide; R, lenalidomide; V, bortezomib.

  • View in gallery

    NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Multiple Myeloma: management of venous thromboembolism in multiple myeloma [MYEL-I, 1 OF 3]. Version 4.2022.

    © 2022 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN®. To view the most recent and complete version of these NCCN Guidelines, go to NCCN.org.

  • 1.

    Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab plus lenalidomide, bortezomib, and dexamethasone in patients with transplant-eligible newly diagnosed multiple myeloma: updated analysis of GRIFFIN after 24 months of maintenance [abstract]. Blood 2021;138(Suppl 1):Abstract 79.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Kumar SK, Callander NS, Adekola K, et al. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 4.2022. Accessed February 28, 2022. To view the most recent version, visit NCCN.org

    • Search Google Scholar
    • Export Citation
  • 3.

    Costa LJ, Chhabra S, Callander NS, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone, autologous transplantation and MRD response-adapted consolidation and treatment cessation. Final primary endpoint analysis of the MASTER Trial [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 481.

    • Search Google Scholar
    • Export Citation
  • 4.

    Perrot A, Lauwers-Cances V, Cazaubiel T, et al. Early versus late autologous stem cell transplant in newly diagnosed multiple myeloma: long-term follow-up analysis of the IFM 2009 trial [abstract]. Blood 2020;136(Suppl 1):Abstract 39.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Gay F, Musto P, Rota-Scalabrini D, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomized, open-label, phase 2 trial. Lancet Oncol 2021;2:17051720.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;10;366:17701781.

  • 7.

    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;35:32793289.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol 2021;22:13781390.

    • Search Google Scholar
    • Export Citation
  • 9.

    Facon T, Kumar SK, Plesner T, et al. Overall survival results with daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study [abstract]. European Hematology Association 2021 Virtual Congress; June 4–17, 2021. Abstract LB1901.

    • Search Google Scholar
    • Export Citation
  • 10.

    Zanwar S, Ho M, Kapoor P, et al. Outcomes of triple class (proteasome inhibitor, IMiDs and monoclonal antibody) refractory patients with multiple myeloma. Leukemia 2022;36:873876.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomized, open-label, phase 3 trial. Lancet 2020;396:15631573.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    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;21:207221.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021;384:705716.

  • 14.

    Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 549.

    • Search Google Scholar
    • Export Citation
  • 15.

    Moreau P, Usmani SZ, Garfall A, et al. Updated results from MajesTEC-1: phase 1/2 study of teclistamab, a B-cell maturation antigen x CD3 bispecific antibody in relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 896.

    • Search Google Scholar
    • Export Citation
  • 16.

    Krishnan A, Minnema MC, Berdeja JG, et al. Updated phase 1 results from MonumenTAL-1: first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody in patients with relapsed/refractory multiple myeloma [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 158.

    • Search Google Scholar
    • Export Citation
  • 17.

    Trudel S, Cohen AD, Krishnan AY, et al. Cevostamab monotherapy continues to show clinically meaningful activity and manageable safety in patients with heavily pretreated relapsed/refractory multiple myeloma: updated results from an ongoing phase I study [abstract]. Presented at the 63rd ASH Annual Meeting & Exposition; December 10–14, 2021; Atlanta, Georgia. Abstract 157.

    • Search Google Scholar
    • Export Citation
  • 18.

    Kumar SK, Harrison SJ, Cavo M, et al. Final overall survival results from BELLINI, a phase 3 study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma [abstract]. Blood 2021;138(Suppl 1):Abstract 84.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Lonial S, Popat R, Hulin C, et al. Iberdomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma: results from, the dose-expansion phase of the CC-220-MM-001 trial [abstract]. Blood 2021;138(Suppl 1):Abstract 162.

    • Crossref
    • Search Google Scholar
    • Export Citation
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