A study showed that the triplet therapy isatuximab, pomalidomide, and dexamethasone (IsaPd) is an option for daratumumab-refractory multiple myeloma (MM), though the “modest” progression-free survival (PFS) gains underscore the need for better treatment options in this patient population.
The study was led by Enrica Antonia Martino, MD, of the Azienda Ospedaliera Annunziata in Italy, and published in Hematological Oncology.
This multicenter, retrospective, real-world study included 51 Italian patients with MM who were daratumumab-refractory. Most were younger than 70 years (60.8%), female (56.9%), and heavily pretreated (74.5% were triple-class refractory). More than half (58.8%) had received prior autologous hematopoietic stem cell transplant.
Patients received the following dose schedule in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal:
- Isatuximab 10 mg/kg intravenously on days one, eight, 15, and 22 of the first cycle then on days one and 15 of subsequent cycles
- Pomalidomide 4 mg orally once daily on days one to 21 of each cycle
- Dexamethasone 40 mg (or 20 mg in patients older than 75 years) weekly
The overall response rate for IsaPd was 56.9% (n=29), including three stringent complete responses (CRs), four CRs, and seven very good partial responses.
Age, number of prior therapies, triple-class-refractory status, and time from daratumumab to IsaPd initiation did not appear to impact response rates.
Median PFS was 5.8 months, and baseline hemoglobin levels appeared to predict PFS outcomes. Patients with a hemoglobin <11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22.0 months in those with higher hemoglobin levels.
Median overall survival was 21.0 months, and lower hemoglobin levels (<11 g/L) were associated with a 10-fold increased risk of mortality.
“[Hemoglobin] levels serve as a crucial predictor of clinical outcomes in this population,” the authors noted.
The study is limited by its small patient population and somewhat limited follow-up (median, 16.8 months).
The authors concluded that the IsaPd combination “offers a viable treatment option for patients who are refractory to [daratumumab]” but cautioned that “PFS remains modest, underscoring the need for novel combination therapies … or sequencing strategies that can further enhance the durability of responses in this refractory population.”
Reference
Martino EA, Derudas D, Rossi E, et al. Efficacy and prognostic indicators of isatuximab, pomalidomide, and dexamethasone (IsaPd) in daratumumab-refractory multiple myeloma patients: a multicenter real-world study. Hematol Oncol. 2025;43(2):e70042. doi:10.1002/hon.70042
