Daratumumab-RVd Demonstrates Clinical Benefits For Certain Patients With Multiple Myeloma

Daratumumab continued to demonstrate deep and durable responses, including improvements to stringent complete response (sCR) rates and minimal residual disease (MRD)-negativity.

A 24-month follow-up analysis of the phase 2 GRIFFIN trial evaluating the addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM) found that daratumumab continued to demonstrate deep and durable responses, including improvements to stringent complete response (sCR) rates and minimal residual disease (MRD)-negativity. Presented at the American Society of Hematology’s 2021 Annual Meeting and Exposition, the data also suggest a trend toward improvement in progression-free survival (PFS).

To conduct the study, 207 patients with NDMM eligible for high-dose therapy (HDT) and ASCT were randomized 1:1 to receive RVd or daratumumab-RVd (D-RVd). Participants were stratified by ISS disease stage and creatinine clearance. The primary endpoint was sCR rate by the end of post-ASCT consolidation, with responses assessed by a validated computer algorithm. Key secondary endpoints included PFS and MRD negativity. Maintenance therapy was conducted with either lenalidomide alone or in combination with daratumumab (D-R).

Following 24 months of D-R or lenalidomide maintenance therapy, the rate of sCR favored D-RVd versus RVd in the response-evaluable population. Further, in the intent-to-treat (ITT) population, MRD-negativity rates remained higher for D-RVd versus RVd, at 64.4% versus 30.1% respectively.

The rate of sustained MRD negativity lasting 12 or more months in the ITT population was more than 3 times higher for D-RVd versus RVd. At 38.6 months follow-up, neither arm reached median PFS, but the data trended toward favoring D-RVd. The estimated 36-month PFS rate was 88.9% for D-RVd and 81.2% for RVd.

Overall, 14 patients died from progressive disease. No new safety concerns were observed with extended follow-up.

Grade 3/4 treatment-emergent adverse events (TEAEs) developed in 86.9% of D-RVd patients and 79.4% of RVd patients. TEAEs resulted in treatment discontinuation in 34.3% of patients in both arms, and 1 patient per group died as a result of TEAEs, neither of which were related to study treatment, according to the researchers.

REFERENCE

Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of Griffin after 24 months of maintenance. Presented at: ASH Annual Meeting and Exposition 2021. Accessed December 9, 2021. https://ash.confex.com/ash/2021/webprogram/Paper149024.html