The addition of daratumumab (D) to standard frontline lenalidomide, bortezomib, and dexamethasone (RVd) induction therapy prior to autologous stem cell transplantation (ASCT) yielded higher rates of stringent complete response (sCR) and minimal residual disease (MRD) negativity compared with RVd in patients with newly diagnosed multiple myeloma (MM), according to results from the phase 2 GRIFFIN trial (ClinicalTrials.gov Identifier, NCT02874742), which was published in Blood.
Eligible patients with newly diagnosed MM (207 patients) were randomly assigned (1:1) to receive 4 cycles of D-RVd or RVd induction, 2 cycles of ASCT, D-RVd or RVd consolidation, and 26 cycles of lenalidomide plus D or lenalidomide maintenance. The primary endpoint was sCR rate by the end of post-ASCT consolidation.
The median patient age was 59 years (range, 29-70 years) in the D-RVd arm and 61 years (range, 40-70 years) in the RVd arm. Other patient and disease characteristics were also well balanced among the arms.
The sCR rate by the end of post-ASCT consolidation was higher in the D-RVd arm compared with the RVd arm (42.4% vs 32.0%; odds ratio, 1.57; 95% CI, 0.87-2.82; 1-sided P =.068; meeting the prespecified 1-sided a of 0.10). The rate of MRD negativity (10-5 threshold) was also higher in the D-RVd arm compared with the RVd arm (21.2% vs 5.8%; P =.0019) in the intent-to-treat population.
At a median follow up of 22.1 months, the responses deepened in both arms. The sCR rates improved to 62.6% for D-RVd and 45.4% for RVd (P =.0177); the MRD negativity rates also improved (51.0% vs 20.4%, respectively; P <.0001).
Neither median progression-free survival (PFS) nor overall survival were reached in either arm. The Kaplan-Meier estimate of the 24-month PFS rates were 95.8% and 89.8% in the D-RVd and RVd arms, respectively. Disease progression occurred in 3.8% and 6.8% of patients in the D-RVd (4 patients) and RVd arm (7 patients), respectively.
No new safety concerns were reported. Grade 3/4 hematologic adverse events were more common with D-RVd compared with RVd (neutropenia, 41.4% vs 21.6%; lymphopenia, 23.2% vs 21.6%; thrombocytopenia, 16.2% vs 8.8%; leukopenia, 16.2% vs 6.9%; anemia, 9.1% vs 5.9%). Infections were more common with D-RVd compared with RVd (90.9% vs 61.8%); however, grade 3/4 infection rates were similar between the arms (23.2% vs 21.6%).
“Study results from GRIFFIN are promising and practice informing; this randomized phase 2 study was designed to expediently provide efficacy and safety information on a new regimen of great interest to myeloma clinicians,” wrote the authors.
These results provide a support for the ongoing phase 3 PERSEUS registration study (ClinicalTrials.gov Identifier: NCT03710603), which is assessing PFS in transplant-eligible patients with newly diagnosed MM receiving D-RVd or RVd.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Voorhees PM, Kaufman JL, Laubach JP, et al. Daratumumab, Lenalidomide, Bortezomib, & Dexamethasone for Transplant-eligible Newly Diagnosed Multiple Myeloma: GRIFFIN. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288