Isatuximab, Carfilzomib, Lenalidomide and Dexamethasone (I-KRd) in front-line treatment of high-risk Multiple Myeloma: Results of the Safety Run-In cohort in the phase II, multicenter GMMG-CONCEPT trial

High-risk multiple myeloma (MM) disease still has a significant impaired prognostic outcome. Achievement of minimal residual disease (MRD) negativity correlates with favorable progression-free (PFS) and overall survival (OS) including high-risk patients. Combination treatment with proteasome inhibitor, immunomodulating agent and dexamethasone in first-line treatment results in high response rates and deep remissions. It was shown, that addition of monoclonal anti-CD38 antibody further improves depth of response and MRD-negative rates. The multicenter, phase II GMMG-CONCEPT trial investigates combination treatment with Isatuximab, Carfilzomib, Lenalidomide and Dexamethasone (I-KRd) for front-line, high-risk MM. Here, we report on the resultsof the safety run-in cohort. 153 patients with newly-diagnosed MM are planned to be included into the trial and receive 6 cycles of I-KRd induction followed by high-dose melphalan, 4 cycles of I-KRd consolidation and I-KR maintenance. The safety-run in phase included the first 10 patients to assess dose-limiting toxicities during the first two I-KRd cycles. In addition, early responses are reported. 10 patients (42-67 years) contributed to the analysis. All patients experienced at least one treatment-emergent adverse event (TEAE), in total 49 TEAE were reported, 15 were classified as Grad 1, 14 as Grade 2, 17 as Grade 3 and 3 as Grade 4. Main ≥ Grade 3 toxicities were hematologic with neutropenia in 6 patients, leukopenia in 5 patients, lymphopenia in 2 patients, anemia in 2 patients and thrombocytopenia in 1 patient. Non-hematological toxicities Grade ≥ 3 were cerebral vascular disorders in 2 patients, self-limiting ventricular tachycardia in 1 patient and diarrhea in 1 patient. 3 patients experienced infusion reaction grade 2 during the first Isatuximab infusion. In total, 5 SAE occurred. The 2 cerebral events were classified as non-related due to preexisting comorbidities. 9/10 patients completed 6 cycles of induction. 10/10 patients had documented responses during induction phase with all patients achieving ≥ VGPR.