Isatuximab provides a clinically meaningful benefit in overall survival (OS) when added to pomalidomide and low-dose dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (MM), according to researchers.
In the final analysis of the phase 3 ICARIA-MM study, isatuximab plus Pd provided a numeric improvement in OS over Pd alone, although the improvement did not reach the prespecified threshold for statistical significance.
Nevertheless, the trial results support isatuximab plus Pd as a standard of care for patients with relapsed/refractory MM, according to study investigator Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston. Dr Richardson presented these results at the 19th International Myeloma Society Annual Meeting.
The ICARIA-MM study (ClinicalTrials.gov Identifier: NCT02990338) included 307 patients with relapsed/refractory MM who were randomly assigned to receive isatuximab plus Pd (n=154) or Pd alone (n=153),
Pd was given at the same dose and frequency in each arm. Isatuximab was given at a dose of 10 mg/kg on days 1, 8, 15, and 22 in cycle 1 and on days 1 and 15 of subsequent cycles. Treatment in either arm was given until disease progression, unacceptable toxicity, or patient request to discontinue.
The median follow-up was 52.4 months in the isatuximab arm and 52.6 months in the Pd arm. The median treatment duration was approximately twice as long in the isatuximab arm as in the Pd-alone arm — 47.57 weeks and 24.00 weeks, respectively.
The median OS was 24.57 months in the isatuximab arm and 17.71 months in the Pd arm (hazard ratio [HR], 0.776; 95% CI, 0.594-1.1015; P =.0319).
Dr Richardson noted that the OS improvement did not reach the prespecified level of statistical significance (P =.02). However, he said, the benefit with isatuximab was “clinically meaningful,” with a median OS improvement of 6.9 months over the comparator arm.
Dr Richardson also pointed out that the COVID-19 pandemic influenced OS outcomes. Four patients died of COVID-19 in the isatuximab arm, but there were no COVID-19-related deaths in the Pd-alone arm.
The median time to next treatment was 15.51 months in the isatuximab arm and 8.87 months in the Pd arm (HR, 0.548; 95% CI, 0.417-0.718). The median second progression-free survival was 17.51 and 12.88 months, respectively (HR, 0.735; 95% CI, 0.569-0.950).
Safety profiles remained consistent with earlier results. There was a higher rate of grade 3 or higher treatment-emergent adverse events (TEAEs) in the isatuximab arm than in the Pd-alone arm — 90.8% and 75.8%, respectively.
However, fatal TEAEs and discontinuations due to TEAEs occurred at similar rates in each arm. The rate of fatal TEAEs was 9.9% in the isatuximab arm and 10.7% in the Pd-alone arm. The rate of discontinuation due to TEAEs was 12.5% and 14.8%, respectively.
Disclosures: This research was supported by Sanofi. Dr Richardson declared affiliations with Oncopeptides, Celgene/Bristol Myers Squibb, Karyopharm, Takeda, Secura Bio, GSK, Regeneron, AstraZeneca, Protocol Intelligence, and Sanofi.
Richardson P, Perrot A, San-Miguel J, et al. Isatuximab plus pomalidomide/low-dose dexamethasone versus pomalidomide/low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (ICARIA-MM): Final overall survival analysis. Presented at IMS 2022; August 25-27, 2022; Abstract OAB-052.