Final Analysis of Phase 2 GRIFFIN Shows Daratumumab Improves PFS After 4 Years

Patients receiving the quadruplet therapy have continued to show improved responses and higher rates of minimal residual disease (MRD) negativity.

Patients with newly diagnosed, transplant-eligible multiple myeloma (NDMM) had improved responses after 4 years if they received daratumumab (Darzalex) in combination with a well-known triplet therapy than patients who received the triplet alone, according to final results of the phase 2 GRIFFIN trial, presented today in Los Angeles, California at the International Myeloma Society Annual Meeting.

The results for GRIFFIN are the latest involving the quadruplet of daratumumab with lenolidomide (Revlimid), bortezomib (Velcade) and dexamethasone (D-RVd) in patients with NDMM who are transplant eligible.

GRIFFIN had 2 phases: 16 patients received the quadruplet that included daratumumab to evaluate safety; then during a maintenance phase from cycles 7-32; the maintenance phase was updated every 28 days based on pharmacokinetic data.

In the subsequent phase 2 part of the study, 207 patients were randomized with RVd induction and consolidation, autologous stem cell transplant (ASCT), and maintenance with either lenalidomide; or D-RVd, ASCT, and maintenance with daratumumab and lenalidomide.

The primary analysis, after a median of 13.5 months, showed GRIFFIN met its primary end point, with a higher percentage of patients taking the D-RVd achieving stringent complete response (sCR) compared with RVd alone by the end of post-autologous stem cell transplant (ASCT) consolidation therapy, 42.4% compared with 32%.

More interim results presented at the American Society of Hematology in December 2021 showed that the patients receiving daratumumab with lenalidomide for maintenance for 24 months had sCR of 66%, vs 47.4% for lenalidomide alone. Minimal residual disease (MRD) negativity rates were higher for the daratumumab arm.

Final results presented in Los Angeles after a median follow-up of 49.6 months—which included all patients completing at least 12 months of follow-up—showed that patients receiving daratumumab continued to have stronger responses, including longer progression free survival. The hazard ratio for the daratumumab patients on PFS was 0.45 (95% CI, 0.21-0.95; P = .0324). Higher MRD negativity rates were seen in the daratumumab arm, and no new safety concerns were reported.

“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,” 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, said in a statement. “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.”

Officials from Janssen Biotech, manufacturer of daratumumab, said the phase 3 PERSEUS study will further evaluate the therapy.