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. 2021 Feb 23;5(4):1092-1096.
doi: 10.1182/bloodadvances.2020003642.

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

Peter M Voorhees  1 , Cesar Rodriguez  2 , Brandi Reeves  3 , Nitya Nathwani  4 , Luciano J Costa  5 , Yana Lutska  6 , Padma Bobba  6 , Daniela Hoehn  6 , Huiling Pei  7 , Jon Ukropec  8 , Ming Qi  9 , Thomas S Lin  6 , Paul G Richardson  10
Affiliations

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

Peter M Voorhees et al. Blood Adv. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: P.M.V. has served on advisory boards for Adaptive Biotechnologies, Bristol Myers Squibb, Janssen, and TeneoBio; has served in a consultancy role for Novartis and Oncopeptides; and has received honoraria from GlaxoSmithKline and Oncopeptides. C.R. has served in a consultancy role or on the speakers’ bureaus for Bristol Myers Squibb, Takeda, and Amgen. B.R. has served on the speakers’ bureau for Bristol Myers Squibb and has received honoraria from Incyte and Takeda. L.J.C. has received research funding from Janssen and Amgen; has received honoraria from Amgen, Celgene, Sanofi, Janssen, and Bristol Myers Squibb; and has served in a consultancy role for Janssen, Amgen, Sanofi, AbbVie, Celgene, Bristol Myers Squibb, and Genentech. Y.L. and P.B. are employees of Janssen. D.H. is an employee of Merck and was an employee of Janssen at the time of the study. J.U. is an employee of Genmab and was an employee of Janssen at the time of the study. H.P., M.Q., and T.S.L. are employees of Janssen and have equity ownership in Johnson & Johnson. P.G.R. has received research funding from Oncopeptides, Celgene, Takeda, and Bristol Myers Squibb; has received honoraria from Janssen, Takeda, Celgene, GlaxoSmithKline, and Secura Bio; has served in a consultancy role for Celgene/Bristol Myers Squibb, Janssen, Karyopharm, Oncopeptides, Sanofi, Secura Bio, Takeda, AbbVie, and GlaxoSmithKline; and has served on the board of directors or held membership on an advisory committee for Jazz Pharmaceuticals. N.N. declares no competing financial interests.

Figures

Figure 1.
Figure 1.
Summary of updated response rates and MRD-negativity rates (10‒5or 10−6threshold) over time for D-RVd in the safety run-in cohort (N = 16) of GRIFFIN. (A) Response rates over time are shown for the response-evaluable population (n = 16). (B) MRD-negativity rates over time are shown for the intent-to-treat population (N = 16). CR, complete response; ORR, overall response rate; PR, partial response; VGPR, very good partial response. *Percentages do not add up to 100% because of rounding.
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