P173 | CLINICAL EFFICACY OF ISATUXIMAB PLUS CARFILZOMIB AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: 2025 DATA UPDATE

Introduction Isatuximab, a novel anti-CD38 monoclonal antibody, has demonstrated significant efficacy in combination with carfilzomib and dexamethasone (Isa-KD) for relapsed/refractory multiple myeloma (RRMM) treatment, as documented in the phase III IKEMA trial. However, real-world evidence on its efficacy and safety remains limited. We present updated results from a multicenter retrospective observational study of Isa-KD in a real-life cohort of RRMM patients. Methods We enrolled 103 RRMM patients treated with Isa-KD between March 2022 and March 2024 across 16 Italian Hematology Units. All patients received Isa-KD outside of clinical trials and had undergone 1–3 prior lines of therapy. High-risk genetic abnormalities and lenalidomide refractoriness were defined according to International Myeloma Working Group (IMWG) criteria. Results Baseline characteristics are summarized in Fig 1A. Our cohort included 38% of patients with high-risk cytogenetic abnormalities and 16% with extramedullary disease (EMD). The median follow-up was 24 months (95%CI, 21–26). Isa-KD was administered as second-line treatment in 67% of cases (n = 69). Prior lenalidomide maintenance was reported in 61% of patients, with a median duration of 23 months. Lenalidomide-refractory and lenalidomide-exposed patients accounted for 19% and 71%, respectively. The overall response rate was 85%, including 18% of patients achieving stringent complete response (sCR) or complete response (CR), and 39% very good partial response. Median progression-free survival (PFS) was 28 months [95% CI, 19-not estimable(NE); Fig.1B], and 24-month overall survival (OS) was 72% (95% CI, 62–81%). Among patients treated with second line therapies, median PFS was not reached (95% CI, 28–NE; Fig 1C), with 24-month PFS and OS of 63% (95% CI, 51–77%) and 75% (95%CI, 65–86%), respectively. Isa-KD was well tolerated with cardiac toxicity (hypertension, 14%; and tachyarrhythmia, 3%) and pneumonia (13%) as the most frequent serious adverse events observed. Conclusion Isa-KD demonstrates high efficacy and manageable toxicity in a real-world RRMM population, including those with adverse features such as high-risk cytogenetics, EMD, and lenalidomide resistance. These findings support the use of Isa-KD as an early-line option in routine practice, particularly for patients typically underrepresented in clinical trials.