DVRd Followed By Ciltacabtagene Autoleucel Versus DVRd Followed By ASCT in Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible: A Randomized Phase 3 Study (<i>EM</i>agine/CARTITUDE-6)

Boccadoro, Mario; San-Miguel, Jesús F.; Suzuki, Kenshi; Donk, Niels W.C.J. van de; Cook, Gordon; Jakubowiak, Andrzej; Madduri, Deepu; Afifi, Salma; Stevens, An-Sofie; Schecter, Jordan M.; Deraedt, William; Kuppens, Steven; Mistry, Pankaj; Pacaud, Lida; Florendo, Erika; Broijl, Annemiek; Gay, Francesca; Mina, Roberto; Rasche, Leo; Moreau, Philippe; Mateos, María‐Victoria; Einsele, Hermann; Sonneveld, Pieter

doi:10.1182/blood-2022-157021

Cited by 8 publications

(4 citation statements)

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“…Fortunately, there are ongoing clinical trials evaluating CAR-T cell therapy for patients with newly diagnosed multiple myeloma (NDMM). For example, the CARTITUDE-6 [61] is a randomized phase 3 study aiming to compare the efficacy of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) followed by cilta-cel and lenalidomide versus DVRd followed by ASCT, DVRd, and lenalidomide. Also, in cases where ASCT is not intended to be the initial therapeutic approach, the CARTITUDE-5 study [62], a randomized phase 3 trial will compare the efficacy of Bortezomib, Lenalidomide, and Dexamethasone (VRd) induction followed by cilta-cel versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance therapy.…”

Section: Discussionmentioning

confidence: 99%

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

Pereira,

Bergantim

2024

IJMS

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Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy’s efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.

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Section: Discussionmentioning

confidence: 99%

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

Pereira,

Bergantim

2024

IJMS

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“…Furthermore, novel consolidation therapies are being explored as potential alternatives to HDM-ASCT. For example, the phase 3 CARTITUDE-6 trial (NCT05257083) [84] is comparing the use of the CAR T cell therapy ciltacabtagene autoleucel with HDM-ASCT in conjunction with six cycles of Dara-RVd and lenalidomide maintenance for 2 years, to determine which approach is superior in terms of PFS and sustained MRD-negative CR rate. Meanwhile, a number of studies are being developed to explore the use of bispecific antibodies such as teclistamab, talquetamab, and elranatamab as alternatives to HDM-ASCT-for example, the phase 2 GEM-TECTAL study (NCT05849610) is investigating intensification therapy with teclistamab plus daratumumab, with or without subsequent talquetamab plus daratumumab, in patients with high-risk NDMM.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Mo,

Hartley-Brown,

Midha

et al. 2023

Cancers

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The standards of care for the initial treatment of patients with newly diagnosed multiple myeloma (NDMM) who are eligible for high-dose melphalan and autologous stem cell transplantation (HDM-ASCT) include highly active triplet and quadruplet regimens based on proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These regimens are resulting in improved outcomes and increasingly high rates of minimal residual disease (MRD)-negative responses without HDM-ASCT as part of the upfront therapy. Furthermore, recent randomized studies have shown that, while transplant-based approaches as a frontline therapy result in significantly longer progression-free survival compared to non-transplant approaches, this has not translated into an overall survival benefit. Given these developments, and in the context of the treatment burden of undergoing HDM-ASCT, in addition to the acute toxicities and long-term sequelae of HDM, which are associated with the genotoxicity of melphalan, there is an increasing rationale for considering deferring upfront HDM-ASCT in select transplant-eligible patients and saving it as a treatment option for later salvage therapy. Here, we review the latest clinical trial data on upfront or deferred HDM-ASCT and on the activity of quadruplet induction regimens, including rates of MRD-negative responses, and summarize emerging treatment approaches in the upfront setting such as the use of MRD-directed therapy and alternatives to HDM-ASCT.

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“…The development of innovative BCMA-targeted immunotherapies as CAR T cells and bispecific antibodies, recently approved for RRMM patients, paved the way for exploring them in upfront setting. In the ongoing phase III EMagine/CARTITUDE-6 trial [ 89 ], that is comparing a cellular therapeutic approach with CAR T cells with conventional ASCT, NDMM patients are randomized to receive either 6 cycles of Dara-VRD followed lymphodepletion and a single cilta-cel infusion or 4 cycles of Dara-VRD as induction followed by ASCT and 2 cycles of Dara-VRD consolidation. In patients aged 60–75 years old, the phase III DSMM XIII study [ 90 ] compared continuous lenalidomide plus dexamethasone (Rd) with Rd as induction followed by ASCT with MEL140 and lenalidomide maintenance.…”

Section: Autologous Stem Cell Transplantation In Light Of New Therapiesmentioning

confidence: 99%

Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

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Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

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DVRd Followed By Ciltacabtagene Autoleucel Versus DVRd Followed By ASCT in Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible: A Randomized Phase 3 Study (EMagine/CARTITUDE-6)

Cited by 8 publications

References 0 publications

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis

Upfront or Deferred Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Triplet and Quadruplet Induction and Minimal Residual Disease/Risk-Adapted Therapy

Current Main Topics in Multiple Myeloma

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