GMMG-CONCEPT: Quadruplet Active in High-Risk, Newly Diagnosed MM
The phase 2 GMMG-CONCEPT trial (Clinicaltrials.gov Identifier NCT03104842) was designed to test the efficacy of isatuximab plus carfilzomib, lenalidomide, and dexamethasone (isa-KRd) in transplant-eligible and -ineligible patients with high-risk MM.4
The treatment for transplant-eligible patients consisted of 6 cycles of isa-KRd induction, followed by high-dose melphalan and ASCT, 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 included 93 patients in the transplant-eligible arm, of whom 63 (67.7%) were MRD negative at the end of consolidation. Of the 24 transplant-ineligible patients, 13 (54.2%) were MRD negative at the end of consolidation.
The ORR was 94.9% in the transplant-eligible arm and 88.5% in the transplant-ineligible arm. The rate of CR/sCR was 72.7% and 57.7%, respectively.
The safety population included 97 patients in the transplant-eligible group and 25 in the transplant-ineligible group. The most frequent AEs (in the transplant-eligible and -ineligible groups, respectively) were neutropenia (41.2% and 28%), leukopenia (25.8% and 4%), thrombocytopenia (27.8% and 20%), infection (60.8% and 48%), gastrointestinal AEs (19.6% and 28%), and infusion-related reactions (26.8% and 16%).
These data support the use of optimized quadruplet therapy as first-line treatment, especially in patients with high-risk MM, said study presenter Katja C. Weisel, MD, of University Medical Center Hamburg-Eppendorf in Germany.
“Data on duration of responses will be interesting to learn in the upcoming months and years … because we know, particularly with high-risk disease, the persistence of the response is just as important,” said Luciano Costa, MD, PhD, of the University of Alabama at Birmingham, who was not involved in this trial.
Disclosures: The MonumenTAL-1 trial and MajesTEC-2 trial are supported by Janssen Research & Development, LLC. The OPTIMUM/MUKnine trial is partly supported by Janssen and Celgene. Dr Shah disclosed relationships with Sanofi, Bristol Myers Squibb, and Janssen. Dr Costa disclosed relationships with Adaptive Biotechnologies, Janssen, Bristol Myers Squibb, Sanofi, Amgen, AbbVie, and Genentech. Dr Chari, Dr Weisel, and some of the other study authors declared affiliations with various companies. Please see the references below for a full list of their disclosures.
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2. Searle E, Quach H, Wong SW, et al. Teclistamab in combination with subcutaneous daratumumab and lenalidomide in patients with multiple myeloma: Results from one cohort of MajesTEC-2, a phase1b, multicohort study. Presented at ASH 2022. December 10-13, 2022. Abstract 160.
3. Kaiser MF, Hall A, Smith I, et al. Extended intensified post-ASCT consolidation with daratumumab, bortezomib, lenalidomide and dexamethasone (Dara-VRd) for ultra-high risk (UHiR) newly diagnosed myeloma (NDMM) and primary plasma cell leukemia (pPCL): The UK Optimum/Muknine Trial. Presented at ASH 2022. December 10-13, 2022. Abstract 758.
4. 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.
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