The addition of isatuximab to pomalidomide and low-dose dexamethasone significantly improved PFS and overall response rate among patients with relapsed or refractory multiple myeloma, according to randomized phase 3 study results presented at ASCO Annual Meeting.
Isatuximab (Sanofi) is a novel anti-CD38 monoclonal antibody with multiple modes of action for killing tumor cells, including direct tumor targeting and immune cell engagement.
A phase 1b study demonstrated the combination of isatuximab, pomalidomide (Pomalyst, Celgene) and dexamethasone was clinically active among and generally well-tolerated by patients with heavily pretreated relapsed or refractory myeloma. In addition, “a striking median PFS” in excess of 17 months was observed in that study, Richardson said.
Richardson and colleagues evaluated whether the addition of isatuximab to pomalidomide and dexamethasone would prolong PFS for this patient population. This was the first randomized phase 3 trial to evaluate the addition of a CD38 antibody to the pomalidomide-dexamethasone backbone.
The open-label, multicenter study included 307 patients (median age, 67 years; range, 36-86) with relapsed or refractory myeloma recruited from 92 centers in 26 countries. All patients had received at least two prior lines of therapy (median, 3; range, 2-11), including lenalidomide (Revlimid, Celgene) and a proteasome inhibitor.
All patients were refractory to their most recent therapy. The majority were refractory to lenalidomide (92.5%) and proteasome inhibitor (75.9%), and 19.5% of patients had high-risk cytogenetics. One-third (33.9%) of patients had estimated glomerular filtration rate less than 60 mL/min/1.73 m2.
Researchers assigned 154 patients to pomalidomide (4 mg orally on days 1 through 21) and dexamethasone (40 mg weekly orally or via IV, or 20 mg for those aged older than 75 years) in 28-day cycles. The other 153 patients received pomalidomide and dexamethasone plus isatuximab (10 mg/kg weekly via IV for the first 4 weeks, then every 2 weeks).
After median follow-up of 11.6 months (95% CI, 11.4-12.2), 65 patients (42.2%) assigned isatuximab and 35 (22.9%) assigned pomalidomide-dexamethasone alone remained on treatment.
Researchers reported longer median PFS in the isatuximab group (11.5 months vs. 6.5 months; HR = 0.59; 95% CI, 0.44-0.81). The PFS benefit appeared consistent by investigator assessment and independent review, as well as across all major subgroups.
The addition of isatuximab to pomalidomide-dexamethasone also conferred a significant improvement in ORR (60.4% vs. 35.3%; P < .0001), very good partial response (27.3% vs. 6.5%), complete response/stringent complete response (4.5% vs. 2%), and near complete response (15.6% vs. 3.3%). Researchers noted the true complete response rate in the isatuximab group was underestimated because of the agent’s interference with M-protein measurement.
Richardson PG, et al. Abstract 8004. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.