P174 | EFFICACY AND SAFETY OF ISATUXIMAB, CARFILZOMIB AND DEXAME-THASONE (ISAKD) IN MULTIPLE MYELOMA PATIENTS AT FIRST RELAPSE AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION AND LENALIDOMIDE MAINTENANCE: RESULTS FROM THE MULTICENTER, REAL-LIFE AENEID STU

In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1–3 prior treatments. Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients with a median age of 62 years (range 43-73) who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy (mainly bortezomib-thalidomide-dexamethasone), autologous stem cell transplantation, and lenalidomide maintenance. The baseline characteristics of patients are summarized in Table 1. After a median follow-up time of 12.9 months (range,1–77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series (19.5%), which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median time to first response and best response was 2 months (range,1-4) and 3 months (range,1-12), respectively. The median time to next treatment was 26.3 months (95%CI:17.2-NA), with a 1-year probability of requiring retreatment of 67.9%. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Our analysis provides support to clinical efficacy and safety of IsaKd as second-line therapy in anti-CD38 naïve or sensitive MM patients, relapsed during lenalidomide maintenance after ASCT; this fully respecting the novel “EHA/EMN 2025 Guidelines” considering IsaKd among the preferred regimens in this specific subset of MM patients along with Cilta-cel and Bela-Pd, currently still not approved in Italy.