Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 18; no. 4; p. 595
• Main Authors: Sgherza, Nicola, Battisti, Olga, Curci, Paola, Conticello, Concetta, Palmieri, Salvatore, Derudas, Daniele, Germano, Candida, Martino, Enrica, Mele, Giuseppe, Della Pepa, Roberta, Fazio, Francesca, Mele, Anna, Rossini, Bernardo, Palazzo, Giulia, Roccotelli, Daniela, Rasola, Simona, Petrucci, Maria, Pastore, Domenico, Tarantini, Giuseppe, Pane, Fabrizio, Gentile, Massimo, Di Raimondo, Francesco, Resta, Emanuela, Musto, Pellegrino
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.04.2025
• Subjects: Apoptosis; autologous stem cell transplantation; Cancer; Care and treatment; Carfilzomib; Cytotoxicity; Dexamethasone; Dosage and administration; Drug therapy, Combination; first-relapsed multiple myeloma; Hematology; Hypertension; Induction therapy; isatuximab–carfilzomib–dexamethasone; lenalidomide resistance; Medical prognosis; Multiple myeloma; Patient outcomes; Relapse; second-line therapy; Stem cell transplantation; Toxicity; Italy; lenalidomide resistance; isatuximab–carfilzomib–dexamethasone; second-line therapy; first-relapsed multiple myeloma; autologous stem cell transplantation
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph18040595

Background: 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. Methods: 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 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, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: 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, which was identified as the only factor significantly affecting the PFS in multivariable analysis. 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. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.