Isatuximab plus carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) can produce deep responses in patients with high-risk, newly diagnosed multiple myeloma (NDMM), according to a phase 2 study presented at the 2022 ASH Annual Meeting.
The study included transplant-eligible and -ineligible patients who received Isa-KRd as induction and consolidation. Both patient groups had deep responses after consolidation, with a majority of patients achieving minimal residual disease (MRD) negativity.
The phase 2 study (GMMG-CONCEPT; ClinicalTrials.gov Identifier: NCT03104842) included 125 patients with high-risk NDMM — 99 transplant-eligible patients (median age, 58 years; range, 35-73) and 26 transplant-ineligible patients (median age, 74 years, range 64-87).
The transplant-eligible patients received 6 cycles of Isa-KRd induction, followed by high-dose melphalan, autologous transplant, 4 cycles of Isa-KRd consolidation, and 26 cycles of Isa-KR maintenance. The transplant-ineligible patients received 8 cycles of Isa-KRd induction, 4 cycles of Isa-KRd consolidation, and 26 cycles of Isa-KR maintenance.
The MRD analysis was conducted in 93 transplant-eligible patients and 24 transplant-ineligible patients. The null hypothesis was that the MRD negativity rate would be 50% or less in the transplant-eligible patients and 30% or less in the transplant-ineligible patients. MRD was evaluated with next-generation flow cytometry (minimum sensitivity threshold of 10-5).
At the end of consolidation, 67.7% of transplant-eligible patients were MRD negative (P =.0004), and 3.2% were MRD positive. For the remaining patients in this group, the time point was not reached (24.7%) or data were missing (4.3%).
Among transplant-ineligible patients, 54.2% were MRD negative (P =.012), and 0% were MRD positive. For the remaining 45.8% of patients in this group, the time point was not reached.
In the transplant-eligible patients, the overall response rate (ORR) was 94.9%, the rate of complete response (CR) or better was 72.7%, and the rate of very good partial response (VGPR) or better was 90.9%.
In the transplant-ineligible patients, the ORR was 88.5%, the rate of CR or better was 57.7%, and the rate of VGPR or better was 88.5%.
The safety population included 122 patients — 97 transplant-eligible and 25 transplant-ineligible patients. Grade 3 or higher treatment-emergent adverse events occurred in 78.4% of the transplant-eligible group and 72% of the transplant-ineligible group.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Weisel KC, Besemer B, Haenel M, et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in patients with high-risk newly diagnosed multiple myeloma: Planned interim analysis of the GMMG-Concept trial. Presented at ASH 2022. December 10-13, 2022. Abstract 759.