Predictors of Outcomes and Efficacy of Isatuximab, Pomalidomide, and Dexamethasone Therapy for Patients With Daratumumab Refractory MM

Isatuximab, pomalidomide, and dexamethasone combination therapy may be beneficial for patients with multiple myeloma (MM) refractory to daratumumab (dara-R), with baseline hemoglobin (Hb) being a key predictor for cancer outcomes, according results from a real-world analysis published in Hematological Oncology.

Patients with MM who were previously treated with daratumumab may develop resistance to available therapies which can lead to shower remission periods and decreased overall survival (OS). Previous research on isatuximab in combination with pomalidomide and dexamethasone has demonstrated efficacy and safety for patients with dara-R MM. Researchers conducted a multicenter, real-world analysis of isatuximab, pomalidomide, and dexamethasone to determine cancer outcomes in patients with MM refractory to daratumumab. The primary end points were progression-free survival (PFS) and overall survival (OS).

Among 51 patients with dara-R MM treated with isatuximab, pomalidomide, and dexamethasone, majority of patients were less than 70 years of age (60.8%) and were mostly female (59.6%). Prior to study enrollment, 37.3% of patients received 2 prior lines of therapy (LOT), 33.3% received 3 prior LOT, and 29.4% received 4 or more LOT, as well as 58.8% of patients having undergone autologous stem cell transplantation.

Overall, 29 patients achieved a partial response (PR) at last follow-up, of which 3 were complete response and 7 a very good partial response.

The median follow-up was 16.8 months (interquartile range [IQR]; 10.5 to 23.2) where 33 patients had disease progression or death. The median PFS was 5.8 months (95% confidence interval [CI], 3.9 to 7.7). Subgroup analysis results revealed patients who received isatuximab, pomalidomide, and dexamethasone as third-line treatment had longer PFS than those who received more than 3 prior LOT (hazard ratio [HR], 2; 95% CI; 0.92 to 4.47, P= .078).

Risk for disease progression was found to be higher among patients who had a Hb of less than 11.8 gr/L (HR, 3.5; 95% CI, 1.5 to 8.4). For patients who had a Hb higher than 11.8 gr/L, the median PDS was 22 months (95% CI, 6.2 to 37.7) compared to 4.6 months (95% CI, 3.0 to 6.3) for patients with an Hb less than 11.8 gr/L. Overall, the median OS was 21 months (95% CI, 19 to 23). Shorter OS was found in patients with Hb less than 11 gr/L, compared with patients who had higher Hb (HR, 10.7; 95% CI, 3 to 37.9).

The researchers concluded, “our findings highlight Hb levels serve as a crucial predictor of clinical outcomes in this population. This biomarker, alongside emerging immune‐based therapeutic approaches, may play a pivotal role in refining treatment strategies and optimizing outcomes for Dara‐R RRMM patients.”

Source:

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. Hematological Oncology. Published online February 3, 2025. doi:10.1002/hon.70042