Daratumumab plus RVd for newly diagnosed multiple myeloma: final analysis of the safety run-in cohort of GRIFFIN

• Published in: Blood advances Vol. 5; no. 4; pp. 1092 - 1096
• Main Authors: Voorhees, Peter M., Rodriguez, Cesar, Reeves, Brandi, Nathwani, Nitya, Costa, Luciano J., Lutska, Yana, Bobba, Padma, Hoehn, Daniela, Pei, Huiling, Ukropec, Jon, Qi, Ming, Lin, Thomas S., Richardson, Paul G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.02.2021; American Society of Hematology
• Subjects: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Dexamethasone - therapeutic use; Humans; Lenalidomide - therapeutic use; Multiple Myeloma - diagnosis; Multiple Myeloma - drug therapy; Stimulus Report
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020003642

The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10−5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10−5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With >3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742. •With >3 years median follow-up, D-RVd achieved durable responses that further deepened with D-R maintenance in the safety run-in cohort.•No new safety concerns were identified with D-RVd after longer follow-up in the safety run-in cohort.