Adding isatuximab to pomalidomide and dexamethasone improves PFS and ORR in RRMM

Results from the randomised, phase 3 ICARIA-MM trial, presented by Prof. Michel Attal (University Institute Cancer Toulouse Oncopole, France), showed that the addition of isatuximab to pomalidomide and low-dose dexamethasone significantly improved progression-free survival (PFS) and the overall response rate in patients with relapsed or refractory multiple myeloma (RRMM) [1].

Isatuximab, an investigational anti-CD38 monoclonal antibody, was previously found to be safe and effective in the treatment of RRMM when combined with pomalidomide and dexamethasone in a phase 1b study. Based on this finding, investigators launched the phase 3 study, which enrolled 307 patients with RRMM who had received at least 2 prior lines of therapy with lenalidomide and a proteasome inhibitor. The patients were then randomised to receive isatuximab and pomalidomide/dexamethasone or pomalidomide/dexamethasone therapy.

Researchers found that at a median follow up of 11.6 months, the median PFS was significantly longer in the isatuximab and pomalidomide/dexamethasone arm compared with the pomalidomide arm (11.5 compared with 6.5 months; HR 0.5; 95% CI 0.44-0.81; P<0.0001). Though median overall survival was not reached in either arm of the trial, a clinically meaningful trend toward improvement was seen with the combination therapy (72% vs 63%).

Also of note, isatuximab combination therapy demonstrated a significantly greater overall response rate, compared with pomalidomide/dexamethasone alone (60% vs 35%, P<0.0001). In additional analyses, isatuximab combination therapy compared with pomalidomide/dexamethasone alone showed a treatment benefit consistent across multiple subgroups, including patients 75 years and older, patients with renal insufficiency, and patients who were refractory to lenalidomide. The results presented above were based on an independent review committee assessment.

In addition, the following results favoured isatuximab combination therapy:

• 
  
  • 
    
    • Isatuximab combination therapy demonstrated significantly higher very good partial response rate compared with pomalidomide/dexamethasone alone (31.8% vs 8.5%, respectively, P<0.0001) and a longer duration of response compared to pomalidomide/dexamethasone alone (median 13.27 vs 11.07 months, respectively). Among patients who achieved a response, isatuximab combination therapy demonstrated faster median time to first response compared with pomalidomide/dexamethasone alone (35 days vs 58 days, respectively).
    • Time to next treatment was longer with isatuximab combination therapy compared pomalidomide/dexamethasone alone (median not reached vs 9.1 months; HR 0.538).
    • Data at the time of analysis showed a trend towards an overall survival benefit associated with isatuximab combination therapy. Final data on overall survival will be reported when available.

The combination treatment was generally manageable, reported Prof. Attal, though the addition of isatuximab to pomalidomide/dexamethasone did increase rates of grade 3 or higher treatment-emergent adverse events (86.8% in isatuximab plus pomalidomide vs 70.5% in pomalidomide). Additionally, isatuximab combination therapy compared with pomalidomide/dexamethasone showed: 7.2% vs 12.8% of patients discontinued due to adverse events, respectively; 7.9% vs 9.4% patients died due to adverse events, respectively; infections of grade ≥3 were seen in 42.8% vs 30.2% of patients, respectively; and grade ≥3 neutropenia was seen in 84.9% (febrile 11.8%) vs 70.1% (febrile 2.0%) of patients, respectively. Infusion reactions were reported in 38.2% (2.6% grade 3-4) of isatuximab combination therapy patients.

1. 
   
   1. Attal M et al. Abstract 824, 24th Congress of the EHA, 13-16 June 2019, Amsterdam, the Netherlands.

 



Posted on 9 August 201918 March 2024