Adding isatuximab to treatment with lenalidomide, bortezomib, and dexamethasone (RVd) improves the rate of minimal residual disease (MRD) negativity in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), phase 3 trial results suggest.
Isatuximab plus RVd should therefore be considered a new standard of care in transplant-eligible patients with NDMM, according to Hartmut Goldschmidt, MD, of the
University Hospital Heidelberg in Germany.
Dr Goldschmidt presented these results at the 2021 American Society of Hematology (ASH) Annual Meeting.
The results come from the phase 3 GMMG-HD7 trial (ClinicalTrials.gov Identifier: NCT03617731), which was designed to compared induction with RVd alone or in combination with isatuximab, followed by autologous stem cell transplant and maintenance with rituximab alone or rituximab plus isatuximab. Dr Goldschmidt presented the results of induction only.
There were 660 patients in the intent-to-treat population — 329 assigned to RVd only and 331 to isatuximab plus RVd. Baseline characteristics were well balanced between the treatment arms. The median age was 59 years (range, 37-70 years) in the isatuximab arm and 60 years (range, 26-70 years) in the RVd-only arm.
The rate of treatment discontinuation during induction was higher in the RVd arm than in the isatuximab arm — 10.6% and 5.4%, respectively (P =.02). The rate of discontinuation due to adverse events (AEs) was similar between the arms — 2.4% and 2.1%, respectively.
In all, 293 patients in the RVd arm and 312 in the isatuximab arm completed induction and continued on to transplant.
The primary endpoint was end-of-induction MRD negativity (10–5), evaluated with next-generation flow cytometry.
The MRD negativity rate was 35.6% in the RVd arm and 50.1% in the isatuximab arm (odds ratio [OR] 1.83; 95% CI, 1.34-2.51, P <.001).
Complete response rates after induction were not significantly different between the RVd and isatuximab arms (21.6% vs 24.2%; P =.46). However, the rate of very good partial response or better was significantly higher in the isatuximab arm than in the RVd arm (77.3% vs 60.5%; P <.001).
Dr Goldschmidt noted that the addition of isatuximab had a limited impact on the safety profile. At least 1 AE of grade 3 or higher occurred in 61.3% of patients in the RVd arm and 63.6% of those in the isatuximab arm.
Common grade 3 or higher AEs (in the RVd and isatuximab arms, respectively) included blood and lymphatic system disorders (16.8% vs 25.8%), infections and infestations (10.4% vs 13.0%), and nervous system disorders (10.1% vs 8.5%).
The rate of serious AEs was comparable between the RVd and isatuximab arms (36.3% and 34.8%, respectively). Eight patients in the RVd arm and 4 in the isatuximab arm died during induction.
Disclosures: This trial was supported, in part, by grants from Sanofi, and Sanofi provided the isatuximab. Celgene/Bristol Myers Squibb provided the lenalidomide. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Goldschmidt H, Mai EK, Nievergall E, et al. Addition of isatuximab to lenalidomide, bortezomib and dexamethasone as induction therapy for newly-diagnosed, transplant-eligible multiple myeloma patients: The phase III GMMG-HD7 trial. Presented at ASH 2021; December 11-14, 2021. Abstract 463.