Results of part B of a phase 1b trial showed that the addition of isatuximab (using the short-duration, fixed-volume infusion method) to standard-of-care VRd was feasible, safe, and effective in patients with NDMM ineligible or with no immediate intent for ASCT.
A 2-part, phase 1b study (NCT02513186) evaluated the efficacy and safety of the anti-CD38 monoclonal antibody isatuximab in combination with bortezomib/lenalidomide/dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible or have no immediate intent for autologous stem-cell transplantation (ASCT). Part A of this phase 1b study showed that a weight-based infusion of isatuximab plus VRd was effective and well-tolerated, with a median infusion duration at first infusion of 3.7 hours. Part B of the trial evaluated isatuximab 10 mg/kg administered as a fixed-volume infusion of 250 mL plus standard doses of VRd; results of part B were presented at the 2021 International Myeloma Workshop and summarized here.
Minimal residual disease (MRD) was assessed by combined next-generation flow cytometry or sequencing methods at a threshold of 10–5. The primary end point of part B was the complete response (CR) rate of isatuximab plus VRd. The data cutoff date was March 17, 2021.
At data cutoff, a total of 46 patients were included in part B of this study, the majority (30 of 46 [65.2%]) of whom continued to receive study treatment. The median age of the study population was 70 years; 8 (17.4%) patients had high-risk cytogenetics. A total of 13 (28.3%) patients were deemed transplant eligible but had no immediate intent for ASCT. Of these, 7 (53.8%) proceeded to mobilization and 6 (46.2%) had apheresis.
The overall response rate was 97.8%, including a CR/stringent CR rate of 35.6% and very good partial response rate of 55.6%. The adjusted CR/stringent CR rate increased to 53.3% following implementation of the SEBIA Hydrashift isatuximab immunofixation assay assessing serum M-protein without isatuximab interference. Of the 45 response-evaluable patients, MRD negativity was achieved by 23 (51.1%) patients.
All patients had ≥1 treatment-emergent adverse events (TEAEs). The most common TEAEs were constipation (69.6%), asthenia (67.4%), diarrhea (56.5%), and peripheral sensory neuropathy (50.0%). Grade ≥3 TEAEs were reported in 32 (69.6%) patients, which were predominantly hematologic toxicities. The most common grade ≥3 hematologic abnormalities were lymphopenia (76.1%) and neutropenia (41.3%). Serious TEAEs were reported in 20 (43.5%) patients; TEAEs resulted in death in 6 (13.0%) patients. Infusion reactions were reported in 13 (28.3%) patients, all of which were grade 1 or 2 in severity.
Results of part B of this phase 1b trial show that the addition of isatuximab (using the short-duration, fixed-volume infusion method) to standard-of-care VRd was feasible, safe, and effective in patients with NDMM ineligible or with no immediate intent for ASCT. Ongoing phase 3 studies are further evaluating the isatuximab plus VRd combination regimen.
Source: Ocio E, Perrot A, Bories P, et al. Update of safety and efficacy of isatuximab short-duration fixed-volume infusion plus bortezomib, lenalidomide, and dexamethasone combined therapy for NDMM ineligible/with no immediate intent for ASCT. Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S3-S4.