Daratumumab-Based Quad Regimen (D-RVd) Improves Depth of Response in Transplant-Eligible NDMM: GRIFFIN Study

Daratumumab, a human CD38 monoclonal antibody, is approved by the US Food and Drug Administration (FDA) as monotherapy and in combination with standard-of-care regimens for multiple myeloma (MM). Most recently, the combination of daratumumab with lenalidomide and dexamethasone was FDA approved for patients with newly diagnosed MM (NDMM) who are not eligible for autologous stem-cell transplant (ASCT).

For patients with NDMM who are eligible for ASCT, lenalidomide, bortezomib, and dexamethasone (RVd) followed by high-dose therapy and consolidation is standard of care in the United States. GRIFFIN is a phase 2, randomized, active-controlled, US-based study of daratumumab plus RVd (D-RVd) compared with RVd in ASCT-eligible NDMM patients. This is the primary analysis of the randomized portion of the GRIFFIN study.

Patients were randomized to RVd with or without daratumumab. They were stratified by International Staging System (ISS) stage and creatinine clearance. Patients received 4 induction cycles, stem-cell mobilization, high-dose therapy, ASCT, 2 consolidation cycles, and maintenance with lenalidomide ± daratumumab for 24 months.

During maintenance (cycles 7-32), patients received lenalidomide 10 mg (or 15 mg in ≥10 cycles if tolerated) on days 1 to 21 of each 28-day cycle with or without daratumumab 16 mg/kg IV every 8 weeks or every 4 weeks (per patient decision). The study’s primary end point was rate of stringent complete response (sCR) by the end of consolidation per International Myeloma Working Group computer algorithm.

A total of 207 patients with NDMM were randomized. Baseline characteristics were well-balanced between arms. Their median age was 60 years (29-70 years), and 48%, 37%, and 14% of patients were ISS stage I, II, and III, respectively.

The study met its primary end point; D-RVd improved the rate of sCR by the end of consolidation: 42.4% versus 32.0% (odds ratio, 1.57; 95% confidence interval, 0.87-2.82; P = .1359) at the preset 2-sided alpha of 0.2. D-RVd also achieved higher overall response (99% vs 92%), very good partial response or better (91% vs 73%), and complete response or better (≥CR) (52% vs 42%) rates versus RVd. The rate of minimal residual disease (MRD) negativity (10^–5 next-generation sequencing) among patients achieving ≥CR was higher with D-RVd versus RVd (59% vs 24%).

At median follow-up of 13.5 months, duration of response, progression-free survival, and overall survival data were not yet mature. Median stem-cell yield was 8.1 × 10⁶ versus 9.4 × 10⁶ cells/kg for D-RVd versus RVd.

There was no difference in the rate of grade 3/4 infections between arms. Infusion reactions occurred in 41% of daratumumab recipients; mainly grade 1 or 2 during the first infusion. 

The study shows that D-RVd induces higher response rates and greater depth of response, including sCR and MRD negativity, compared with RVd. The overall safety profile of D-RVd is consistent with previous reports, and stem-cell mobilization and ASCT are feasible. Assessment of the effect of daratumumab maintenance on sCR improvement and MRD rates continues.

Abstract OAB-87: Voorhees P, Kaufman JL, Laubach J, et al. Daratumumab + Lenalidomide, Bortezomib & Dexamethasone Improves Depth of Response in Transplant-Eligible Newly Diagnosed Multiple Myeloma: GRIFFIN