Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab‐Refractory Multiple Myeloma Patients: A Multicenter Real‐World Study
Enrica Antonia Martino, Daniele Derudas, Elena Rossi, Paola Stefanoni, Silvia Mangiacavalli, Elena Zamagni, Massimo Offidani, Anna Furlan, Angela Maria Quinto, Roberta Della Pepa, Giuseppe Bertuglia, Emiliano Barbieri, Concetta Conticello, Claudio De Magistris, Velia Bongarzoni, Anna Maria Cafro, Anna Mele, Cirino Botta, Nicola Sgherza, Giuseppe Mele, Ombretta Annibali, Angela Rago, Raffaele Fontana, Ernesto Vigna, Antonella Bruzzese, Katia Mancuso, Angela Amendola, Annalisa Citro, Emilia Cotzia, Sonia Morè, Elena Rivolti, Loredana Pettine, Mónica Galli, Valerio De Stefano, Maria Teresa Petrucci, Alessandro Corso, Antonino Neri, Francesco Di Raimondo, Niccolò Bolli, Pellegrino Musto, Fortunato Morabito, Massimo Gentile
Abstract
This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.9%), and heavily pretreated, with 74.5% being triple-class refractory (TCR); 32.1% of the 28 patients with cytogenetic data had high-risk abnormalities. The overall response rate (ORR) was 56.9%, including 3 patients with stringent complete response (sCR), 4 with CR, and 7 with very good partial response (VGPR). Neither age, number of prior therapies, TCR status, nor time from Dara refractoriness to IsaPd initiation significantly affected response rates. Median progression-free survival (PFS) was 5.8 months, with a 12-month PFS probability of 30.6%. Baseline hemoglobin (Hb) levels were a key predictor of PFS: patients with Hb < 11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22 months in those with higher Hb. Median overall survival (OS) was 21.0 months, with a 12-month OS probability of 63.4%. Lower Hb levels (< 11 g/L) were associated with a tenfold increased risk of mortality. Among the 28 patients who underwent FISH analysis, while no significant difference in mortality risk was observed, those with high-risk cytogenetic abnormalities exhibited a nearly tenfold increased risk of disease progression. These results suggest that IsaPd offers a meaningful option for Dara-R patients, with Hb levels serving as a critical predictor of both PFS and OS. However, PFS remains modest, underscoring the need for novel combination therapies.