Benefit of Daratumumab Plus RVd Is Maintained Without Additional Toxicities Among Black Patients With NDMM

Ajay K. Nooka MD, MPH, FACP

A subgroup analysis of the phase 2 GRIFFIN trial (NCT02874742) confirmed that Black patients with newly diagnosed multiple myeloma elicited a benefit from treatment with daratumumab (Darzalex) added to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) without additional toxicities. The data were presented in a poster at the 19th International Myeloma Society Annual Meeting.¹

Subgroup analyses were conducted to examine safety and efficacy outcomes of Black and White patients after 2 years of maintenance therapy and included approximately 1 year of additional follow-up (median, 38.6 months).

Among 161 White patients (78%), 85 received D-RVd and 76 received RVd. Among 32 Black patients (15%), 14 received D-RVd and 18 received with RVd. The stringent complete response (sCR) rates were consistently higher for D-RVd compared with RVd in both groups. However, Black patients had higher rates of sCR which deepened over time. Following 1 year of maintenance therapy, the sCR rate with D-VRd was 86% for Black patients compared with 93% after 2 years. Among White patients the 1-year and 2-year post maintenance sCR rates were 61% and 64%, respectively.

After 2 years of maintenance, the complete response (CR) or better rates were 100% for D-RVd vs 62% for RVd in Black patients (P = .0046) compared with 80% and 62%, respectively, for White patients (P = .0166). D-RVd reduced the risk of disease progression or death by 65% in Black patients (HR, 0.35; 95% CI, 0.04-3.39; P = .3441) and 45% in White patients (HR, 0.55; 95% CI, 0.22-1.40; P = .2022). The estimated progression-free survival rates after 36 months were 89% with D-RVd and 86% with RVd for White patients and 92% and 78%, respectively, for Black patients. MRD-negativity rates (10-5) for D-RVd and RVd were 64% vs 22% (P = .0293) for Black patients and 66% with D-RVd vs 32% with RVd for White patients (P < .0001).

“After 2 years of maintenance therapy the addition of daratumumab to the front-line arbitrary treatment for transplant-eligible patients with NDMM improved objective response including the rates of sCR and MRD [minimal residual disease]-negativity in both the Black [and] White patients,” Ajay K. Nooka, MD, MPH, said in a presentation of the data. Nooka is an associate professor in the Department of Hematology and Medical Oncology and director of the Myeloma Program at Emory University, as well as the scientific director of the Winship Data and Technology Applications Shared Resource at Winship Cancer Institute of Emory University in Atlanta, Georgia.

In GRIFFIN, transplant-eligible patients aged 18 to 70 years with NDMM were enrolled and randomly 1:1 to D-RVd or RVd induction for 4 cycles followed by autologous stem cell transplant. Consolidation therapy was administered for 2 cycles and was followed by up to 2 years of maintenance therapy with lenalidomide and daratumumab in the D-RVd cohort or lenalidomide alone in the RVd cohort.^1,2

Daratumumab is a human lgGk monoclonal antibody that targets CD38 with a direct on-tumor and immunomodulatory mechanism of action; it demonstrates a higher cytotoxicity ex vivo toward multiple myeloma (MM) cells compared with other CD38 antibodies and is approved in combination with standard of care regiments to treat MM.^1,2

With a median follow-up of 13.5 months, patients in the primary analysis of GRIFFIN had a sCR of 42.4% with D-RVd (n = 104) treatment compared with 32% with RVd (n = 103; P = .068).2 In updated data presented at the IMS Annual Meeting, benefit with D-RVd was maintained. At a median follow-up of 49.6 months the hazard ratio was 0.45 (95% CI, 0.21-0.95; P .0324).³

The subgroup analysis also confirmed that a tolerable safety profile was maintained. Safety data were available for 14 Black patients who received d-RVd and 18 patients who received RVd. Grade 3/4 TEAEs were reported among 79% and 89% of patients in the investigative and control arms, respectively, with 1 patient in each arm experiencing grade 3/4 peripheral neuropathy. The most common serious treatment-emergent adverse event (TEAE) was pneumonia (21% in D-RVd vs 17% in RVd). Common any-grade TEAEs were peripheral neuropathy (57% vs 67%, respectively), neutropenia (50% vs 20%), lymphopenia (29% vs 39%), thrombocytopenia (29% vs 11%), leukopenia (21% vs 6%), and pneumonia (21% vs 17%).

Among White patients, safety data were available for 83 patients in the D-RVd cohort and 74 patients in the RVd cohort. Grade 3/4 TEAEs were reported among 88% and 76% of patients in the investigative and control arms, respectively, with 5 and 6, respectively, experiencing grade 3/4 peripheral neuropathy. Pneumonia was reported as a serious TEAE in 12% of patients receiving D-RVd vs 15% receiving RVd. Common any-grade TEAEs were peripheral neuropathy (64% vs 78%, respectively), neutropenia (47% vs 19%), lymphopenia (23% vs 16%), thrombocytopenia (13% vs 8%), leukopenia (17% vs 5%), and pneumonia (8% vs 15%).

The authors concluded that larger studies of daratumumab combination therapy are needed to confirm the benefit among Black patients with NDMM.

References

1. Nooka AK, Kaufman JL, Rodriguez C, et al. Daratumumab (DARA) + lenalidomide/bortezomib/dexamethasone (RVd) in Black patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): an updated subgroup analysis of GRIFFIN. Presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA
2. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(suppl 8):936-945. doi:10.1182/blood.2020005288
3. Sborov DW, Laubach J, Kaufman JL, et al. Daratumumab (dara) + lenalidomide, bortezomib, and dexamethasone (RVd) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): final analysis of GRIFFIN. Presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA. Abstract OAB-057