Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study

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.

Keywords: dara‐refractory; dexamethasone; isatuximab; multiple myeloma; pomalidomide; salvage therapy.