Drug Duo Enhances Myeloma Outcomes

TOPLINE:

Adding daratumumab to lenalidomide maintenance therapy after transplant in patients with multiple myeloma triples the minimal residual disease (MRD)–negative conversion rate to 50.5% vs 18.8% with lenalidomide alone. The combination therapy reduces progression risk by 47% and achieves estimated 30-month progression-free survival (PFS) rates of 82.7% vs 66.4% for lenalidomide alone.

METHODOLOGY:

• A multicenter, randomized, open-label, active-controlled, phase 3 trial enrolled 200 patients between June 2019 and May 2023 from 52 sites across the United States and Canada.
• Participants with newly diagnosed multiple myeloma (NDMM) who achieved very good partial response (VGPR) or better, were MRD-positive and anti-CD38–naive after transplant, were randomly assigned 1:1 to daratumumab plus lenalidomide or lenalidomide maintenance.
• Treatment protocol included 10 mg lenalidomide daily through day 28 of each 28-day cycle, with a potential increase to 15 mg after 3 cycles, while the daratumumab group also received 1800 mg subcutaneous injections weekly during cycles 1-2, biweekly during cycles 3-6, and monthly thereafter.
• The primary endpoint measured MRD-negative conversion rate by next-generation sequencing from baseline to 12 months after maintenance treatment initiation, before disease progression or subsequent therapy.

TAKEAWAY:

• MRD-negative conversion rate by 12 months was significantly higher with daratumumab plus lenalidomide vs lenalidomide alone (50.5% vs 18.8%; odds ratio [OR], 4.51; 95% CI, 2.37-8.57; P
• Overall MRD-negative conversion rate at median follow-up of 32.3 months favored the combination therapy (60.6% vs 27.7%; OR, 4.12; 95% CI, 2.26-7.52; P
• PFS analysis showed a 47% risk reduction with combination therapy (hazard ratio, 0.53; 95% CI, 0.29-0.97) and higher estimated 30-month rates (82.7% vs 66.4%).
• Complete response rates or better were superior with combination therapy vs lenalidomide alone (75.8% vs 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P = .0255).

IN PRACTICE:

“Among transplant-eligible patients with NDMM who had ≥ VGPR, were MRD-positive after ASCT, and were anti-CD38–naive, the addition of daratumumab to SoC R maintenance resulted in improved rates of MRD-negative conversion, deeper responses, and improved PFS rates…No new safety concerns were observed,” wrote the authors of the study.

SOURCE:

The study was led by Ashraf Badros, Greenebaum Comprehensive Cancer Center, University of Maryland in Baltimore. It was published online in Blood.

LIMITATIONS:

According to the authors, recruitment challenges arose from the COVID-19 pandemic and increased use of daratumumab during induction. Nearly 10% of patients in each treatment arm had unknown cytogenetic risk, and there was an imbalance in patients with high cytogenetic risk between the treatment arms at diagnosis (23.9% vs 16.9%). Additionally, many patients have not yet reached both the 24- and 36-month MRD assessments, requiring longer follow-up for sustained negativity rates.

DISCLOSURES:

The study was supported by Janssen Biotech, Inc. Badros disclosed receiving research funding from Bristol Myers Squibb, GSK, BeiGene, Roche, and Janssen Pharmaceuticals. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.