Adding isatuximab to treatment with pomalidomide and dexamethasone may significantly improve progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (R/R MM), according to results from the phase 3 ICARIA-MM trial (ClinicalTrials.gov Identifier: NCT02990338) published recently in The Lancet.
Isatuximab is a monoclonal antibody that binds the CD38 receptor, eliciting an antitumor response via several mechanisms of action. It offers a new treatment option for the management of R/R MM and is particularly promising for patients refractory to lenalidomide and a proteasome inhibitor.
ICARIA-MM was a randomized, multicenter, open-label, phase 3 trial in patients with R/R MM who had received at least 2 prior lines of therapy that included lenalidomide and a proteasome inhibitor.
Between January 2017 and February 2018, 307 patients were randomly assigned to receive isatuximab with pomalidomide and dexamethasone (154 patients) or pomalidomide and dexamethasone alone (153 patients).
After median follow-up of 11.6 months, patients who received isatuximab had a median progression-free survival (PFS) of 11.5 months (95% CI, 8.9-13.9), compared with 6.5 months (95% CI, 4.5-8.3) in the nonisatuximab arm (hazard ratio, 0.596; 95% CI, 0.44-0.81; P =.001).
The most frequent all-grade treatment-emergent adverse events (AEs) were: infusion-related reactions at 38% in the isatuximab arm and 0% in the control arm; upper respiratory tract infections at 28% in the isatuximab arm and 17% in the control arm; and diarrhea at 26% in the isatuximab arm and 20% in the control arm.
Fatal AEs were reported in 8% of patients in the isatuximab arm and 9% of patients in the control arm. Treatment-related fatal AEs were reported in 1 patient (sepsis) in the isatuximab arm and 2 patients (pneumonia and urinary tract infection) in the control arm.
The resarchers noted that because this study excluded patients refractory to another monoclonal antibody against CD38, they could not assess the treatment regimen in anti-CD38-refractory patients.
“Although data from other ongoing combination studies of isatuximab are awaited, the findings of this first phase 3 study of an anti-CD38 antibody with pomalidomide and dexamethasone represent an important advance in the management of R/R MM and so provide an active new treatment regimen for these patients who represent an otherwise unmet medical need,” concluded the researchers.
- Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study [published online November 14, 2019]. Lancet. doi:10.1016/S0140-6736(19)32556-5