MRD-Adapted Treatment of Multiple Myeloma Is Feasible for Most Patients

For patients with multiple myeloma (MM) without high-risk chromosome abnormalities, the use of minimal residual disease (MRD) negativity to guide treatment duration and cessation was feasible, with most patients remaining MRD negative at the time of data analysis of a phase 2 trial.

The results of the final analysis of the study were published in Lancet Haematology. However, many patients with high-risk chromosome abnormalities experienced disease recurrence despite achieving MRD negativity.

“Outcomes for patients with ultra-high-risk MM…remain unsatisfactory, and these patients should be prioritized for trials with early induction of therapies with novel mechanisms of action,” the authors wrote in their report.

The multicenter, single-arm, phase 2 MASTER trial (ClinicalTrials.gov Identifier: NCT03224507) treated 123 patients with newly diagnosed MM with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd).

MRD was assessed by next-generation sequencing after or during induction, autologous hematopoietic stem cell transplant, and consolidation. Treatment was stopped when patients achieved MRD negativity for 2 consecutive tests. Patients who did not achieve MRD negativity received lenalidomide maintenance.

At baseline, the median age was 61, with 20% of patients aged 70 or older. There were 20% of patients who were non-Hispanic Black, 76% who were non-Hispanic White, and 3% who were another race/ethnicity. The most common cytogenetic abnormality was a 13q deletion, hyperdiploidy, gain or amplification of 1q, and a 17p deletion. There were 50% of patients who received 1 cycle of bortezomib with or without cyclophosphamide with or without dexamethasone.

MRD negativity was achieved by 81% of evaluable patients, which included 78% of patients without high-risk chromosomal aberrations, 86% with 1 aberration, and 79% of patients with 2 or more aberrations. The progression-free survival (PFS) at 36 months was 88%, 79%, and 50% for patients with none, 1, or 2 or more chromosomal aberrations, respectively, and overall survival (OS) was 97%, 93%, and 100%, respectively.

There was a total of 71% of patients who discontinued treatment and entered MRD surveillance. Of these patients, the cumulative incidence of progression from cessation of therapy at 24 months was 9% for patients with 1 or less high-risk chromosomal aberrations and 47% for patients with 2 or more.

At the time of data analysis, there were 52% of patients who achieved MRD negativity and 73% of patients who discontinued treatment and entered MRD surveillance who remained free of therapy. Of the patients in MRD surveillance, 27% resumed therapy due to MRD detection or disease progression without MRD resurgence.

“This approach provided positive outcomes and a pathway for treatment cessation in most patients with newly diagnosed MM,” the study authors concluded.

Disclosures: This study was supported by Amgen and Janssen Pharmaceuticals. Please see the original reference for a full list of disclosures.

Reference
Costa LJ, Chabra S, Medvedova E, et al. Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial. Lancet Haematol. Published online September 27, 2023. doi: 10.1016/S2352-3026(23)00236-3

This article originally appeared on Hematology Advisor