The randomized phase II GRIFFIN study evaluated the investigational use of daratumumab in combination with lenalidomide, bortezomib, and dexamethasone (RVd), followed by maintenance therapy with daratumumab and lenalidomide, compared to RVd followed by maintenance therapy with lenalidomide alone, in newly diagnosed, transplant-eligible patients with multiple myeloma. Final results of the trial were presented during the Plenary Session at the 19th International Myeloma Society Annual Meeting (Abstract OAB-057).
In the primary analysis (median follow-up = 13.5 months), the GRIFFIN study met its primary endpoint, resulting in a higher stringent complete response rate for daratumumab/RVd compared with RVd alone by the end of post–autologous stem cell transplant (ASCT) consolidation therapy (42.4% vs 32%, 1-sided P = .0680), meeting the prespecified 1-sided alpha of 0.1. The predefined final analysis for GRIFFIN (median follow-up = 49.6 months), which occurred after all patients had completed at least 1 year of follow-up after end-of-study therapy or withdrew, showed that longer progression-free survival was observed in patients who received daratumumab/RVd or daratumumab/lenalidomide compared to those who received RVd/lenalidomide (hazard ratio = 0.45; 95% confidence interval = 0.21–0.95, P = .0324). Higher measurable residual disease (MRD) negativity rates were observed for daratumumab/RVd vs RVd (64% vs 30%). No new safety concerns were observed with longer-term follow-up.
"The final analysis of the GRIFFIN trial highlights the potential benefit of adding daratumumab to RVd for the treatment of newly diagnosed, transplant-eligible patients," said Douglas W. Sborov, MD, MS, Director of the Multiple Myeloma Program at the Huntsman Cancer Institute at the University of Utah and GRIFFIN study investigator. "We are constantly investigating the role of new regimens and combinations to improve outcomes in our patients, and GRIFFIN is another important step forward in this research."
Final Analysis from GRIFFIN
After 2 years of maintenance therapy, the MRD negativity rate continued to favor daratumumab/RVd vs RVd (64% vs 30%, P = <.0001). Additionally, 44% of patients who received daratumumab/RVd achieved sustained MRD negativity of 12 months or more, compared to 14% of patients in the RVd arm. Treatment with daratumumab/RVd also resulted in higher stringent complete response rates at all time points in the study, with the highest rates occurring following 2 years of maintenance therapy (67% vs 48%, P = .0079, respectively). Complete response or better rate was 83% in the daratumumab/RVd arm vs 60% in the RVd arm (P = .005).
At the conclusion of the final analysis, after a median follow-up of 49.6 months, a 55% reduction in the risk of disease progression or death was observed in patients in the daratumumab/RVd arm; an estimated 48-month progression-free survival rate of 87.2% was observed in the daratumumab/RVd arm, compared to 70% in the RVd arm. Median progression-free survival was not reached in either treatment arm. In addition, after extended follow-up, no new safety concerns were observed.
“The phase II GRIFFIN study showed important results with the investigational daratumumab quadruplet regimen in the treatment of newly diagnosed, transplant-eligible multiple myeloma,” said Imran Khan, MD, PhD, U.S. Vice President, Medical Affairs, Hematology at Janssen Scientific Affairs, LLC. "The evaluation of this treatment regimen will continue as part of the registrational phase III PERSEUS study….”
About the GRIFFIN Study
The phase II GRIFFIN study evaluated the investigational regimen of daratumumab in combination with RVd and enrolled and treated more than 200 adults aged 18 to 70 years with newly diagnosed multiple myeloma who were eligible for ASCT. In the safety run-in cohort, 16 patients received 25 mg of lenalidomide orally on days 1 to 14; 1.3 mg/m2 of bortezomib subcutaneously on days 1, 4, 8, and 11; and 20 mg of dexamethasone on days 1, 2, 8, 9, 15, and 16, and every 21 days during the induction and consolidation phases (cycles 1–6). Intravenous (IV) daratumumab at 16 mg/kg was given on days 1, 8, and 15 of cycles 1 to 4 and on day 1 of cycles 5 to 6.
During the maintenance phase (cycles 7–32), patients received 10 mg daily of lenalidomide (15 mg beginning at cycle 10 if tolerated) on days 1 to 21 every 28 days and daratumumab at 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every-4-week maintenance dosing. Maintenance therapy with lenalidomide could be continued beyond cycle 32, per local standard of care.
In the subsequent randomized phase II portion of the study, 207 patients were randomly assigned to treatment with RVd induction and consolidation, ASCT, and maintenance therapy with lenalidomide; or daratumumab/RVd, ASCT, and maintenance therapy with daratumumab and lenalidomide.
