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How to sequence BCMA-directed therapies in early relapsed/ refractory multiple myeloma
At the ESH 7th Translational Research Conference:
Multiple Myeloma
with Martin Kaiser, Mohamad Mohty, and Rakesh Popat
Saturday, October 5, 2024 | 09:10-10:10 CEST
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Quadruplet induction therapy consisting of daratumumab, carfilzomib, lenalidomide, and dexamethasone has shown durable depth and duration of responses in patients with newly diagnosed multiple myeloma, including those treated with autologous stem cell transplantation (ASCT).1 However, the clinical benefit of continuous quadruplet therapy after transplant and its associated patient response has yet to be fully explored.1
In order to bridge this knowledge gap, Costa1 carried out the MASTER trial (NCT03224507), which aimed to determine the rate of measurable residual disease (MRD) negative responses with quadruplet induction therapy and a response-adapted consolidation. We summarize the final analysis presented at the European Hematology Association 2023 Hybrid Congress. For prior results and more information on the MASTER trial, check out our previous article here.
Figure 1. Rates of overall MRD and sustained MRD after 12 months according to the number of high-risk cytogenetic abnormalities*
MRD, measurable residual disease.
*Adapted from Costa.1
Figure 2. Rates of 3-year OS and 3-year PFS according to the number of high-risk cytogenetic abnormalities*
OS, overall survival; PFS, progression-free survival.
*Adapted from Costa.1
Figure 3. Rates of 3-year OS and 3-year PFS according to the number of high-risk cytogenetic abnormalities in patients who achieved an MRD-negative treatment-free state*
MRD, measurable residual disease; OS, overall survival; PFS, progression-free survival.
*Adapted from Costa.1
In patients reaching MRD-SURE status (N = 84):
The adverse events reported in this final analysis did not differ much from previous reports, with 74% of patients experiencing an adverse event of Grade 3 or greater (for further details, see here). Additionally:
The final results from the MASTER trial show durable clinical responses for quadruplet induction therapy, with most patients who achieved treatment cessation having standard or high-risk cytogenetics. Moreover, around 80% of patients with either zero or one high-risk cytogenetic abnormality achieved MRD negativity. In contrast, achieving a sustained MRD-negative status in patients with ultra-high-risk cytogenetics remains an important unmet need. Future directions should now include new agents and mechanisms of action directed towards patients with persistent MRD as well as exploring the possibility of deferring ASCT in early MRD-negative patients.
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