Adding isatuximab to lenalidomide, bortezomib, and dexamethasone (RVd) improves the rate of minimal residual disease (MRD) negativity in patients with newly diagnosed, transplant-eligible multiple myeloma, according to results of a phase 3 trial published in The Lancet Haematology.
“[O]ur results show that addition of the anti-CD38 monoclonal antibody isatuximab to lenalidomide, bortezomib, and dexamethasone is a new standard of care induction regimen in this patient population,” the researchers wrote.
This phase 3 trial (GMMG-HD7; ClinicalTrials.gov Identifier: NCT03617731) included 660 patients with newly diagnosed multiple myeloma who were eligible for transplant. The median age at baseline was 59 years, 38% of patients were women, and 99% were White.
The patients were randomly assigned to receive induction with isatuximab plus RVd or RVd alone for three 42-day cycles. The primary endpoint was MRD negativity by flow cytometry.
The rate of MRD negativity was significantly higher in the isatuximab arm than in the control arm — 50% and 36%, respectively (odds ratio [OR], 1.82; 95% CI, 1.33-2.48; P =.00017). However, MRD data were not available for 11% of patients in the isatuximab arm and 15% of those in the control arm.
The rate of complete response was similar between the isatuximab and control arms — 24% and 22%, respectively (OR, 1.12; 95% CI, 0.77-1.63; P =.58). However, 77% of patients in the isatuximab arm achieved a very good partial response compared with 61% in the control arm (OR, 2.13; 95% CI, 1.50-3.05; P <.0001).
In a post hoc analysis, 47% of patients treated with isatuximab and 32% treated with RVd alone achieved a very good partial response or better as well as MRD negativity (OR, 1.93; 95% CI, 1.39-2.68; P <.0001).
Grade 3-4 adverse events (AEs) occurred in 63% of patients in the isatuximab arm and 61% of those in the control arm. The most common grade 3-4 AEs (in the isatuximab and control groups, respectively) were blood and lymphatic system disorders (26% vs 17%), investigations (24% vs 23%), neutropenia (23% vs 7%), lymphopenia (15% vs 20%), and infections and infestations (12% vs 10%).
There was 1 treatment-related death in the isatuximab arm (septic shock), and there were 4 treatment-related deaths in the control arm (cardiac decompensation, cardiac arrest, drug-induced enteritis, and hepatic and renal failure).
Disclosures: This study was funded by Sanofi. Isatuximab was provided by Sanofi, and lenalidomide was provided by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Goldschmidt H, Mai EK, Bertsch U, et al. Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed,transplantation-eligible patients with multiple myeloma (GMMG-HD7): Part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Lancet Haematol. Published online November 1, 2022. doi:10.1016/S2352-3026(22)00263-0