Daratumumab in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis of Clinically Relevant Subgroups in Griffin

Authors

Ajai Chari
Jonathan L Kaufman
Jacob Laubach
Douglas W Sborov
Brandi Reeves
Cesar Rodriguez
Rebecca Silbermann
Luciano J Costa
Larry D Anderson
Nitya Nathwani
Nina Shah
Naresh Bumma
Sarah A Holstein
Caitlin Costello
Andrzej Jakubowiak
Tanya M Wildes
Robert Z Orlowski
Kenneth H Shain
Andrew J Cowan
Huiling Pei
Annelore Cortoos
Sharmila Patel
Thomas S Lin
Peter M Voorhees
Saad Z Usmani
Paul G Richardson

Publication Date

7-8-2024

Journal

Blood Cancer Journal

Abstract

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a trend toward improved progression-free survival versus RVd (hazard ratio [95% confidence interval]) in patients ≥ 65 years (0.29 [0.06–1.48]), with HRCAs (0.38 [0.14–1.01]), and with gain/amp(1q21) (0.42 [0.14–1.27]). In the functional high-risk subgroup (not MRD negative at the end of consolidation), the hazard ratio was 0.82 (0.35–1.89). Among patients ≥ 65 years, grade 3/4 treatment-emergent adverse event (TEAE) rates were higher for D-RVd versus RVd (88.9% vs 77.8%), as were TEAEs leading to discontinuation of ≥ 1 treatment component (37.0% vs 25.9%). One D-RVd patient died due to an unrelated TEAE. These results support the addition of daratumumab to RVd in transplant-eligible patients with high-risk NDMM. Download video file.(80M, mp4)

Keywords

Adult, Aged, Female, Humans, Male, Middle Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Dexamethasone, Lenalidomide, Multiple Myeloma

Comments

Supplementary Materials

Data Availability Statement

PMID: 38977707