Researchers evaluated survival and infusion time with combination isatuximab, pomalidomide, and low-dose dexamethasone vs pomalidomide plus low-dose dexamethasone alone in relapsed or refractory multiple myeloma.
The three-drug regimen of isatuximab, pomalidomide, and low-dose dexamethasone, almost doubled the progression-free survival of patients with relapsed or refractory multiple myeloma compared with pomalidomide plus low-dose dexamethasone alone.
Based on these results, presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, isatuximab may represent an important new treatment option for relapsed, refractory disease, according to presenter Paul G. Richardson, MD, of Dana-Farber Cancer Institute.
The study (abstract 8004) included 307 patients with myeloma who had received two or more prior lines of therapy, including lenalidomide (93.5% refractory) and a proteasome inhibitor. Patients were randomly assigned to isatuximab plus pomalidomide and low-dose dexamethasone or to pomalidomide plus low-dose dexamethasone alone. About 20% of patients had a high-risk cytogenetic profile at baseline. The primary endpoint was progression-free survival.
The median duration of follow-up was 11.6 months; 42.2% of patients on the isatuximab arm and 22.9% on the pomalidomide/dexamethasone arm are still on treatment.
Median progression-free survival was 11.53 months for patients assigned the three-drug combination compared with 6.47 months for patients assigned pomalidomide/dexamethasone alone (hazard ratio [HR], 0.596; 95% CI, 0.436–0.814; P = .001), an improvement Richardson called clinically meaningful.
This improvement in progression-free survival was consistent when evaluated by the Independent Review Committee and investigator assessment (11.14 vs 6.54 months; HR, 0.602; 95% CI, 0.444–0.816; P = .0009).
Overall response rate was also significantly improved with the three-drug combination compared with the two-drug regimen (60.4% vs 35.3%; P < .0001). Very good partial response or better was observed in 31.8% of patients assigned the three-drug regimen compared with 8.5% of patients assigned the two-drug regimen (P < .0001). Median time to first response was 35 days for the isatuximab arm compared with 58 days for the comparator arm.
Median overall survival has not yet been reached in either treatment arm; however, there was a trend in overall survival benefit observed in the isatuximab arm at an interim analysis.
Time to next treatment was significantly delayed in the three-drug arm compared with the two-drug arm (not reached vs 9.1 months).
The safety profile was favorable overall. There were more grade 3 or worse treatment-emergent adverse events in the isatuximab arm, but the addition of isatuximab did not increase mortality or events leading to discontinuation, according to the presentation. Isatuximab fusion time decreased from 3.3 hours at first infusion to 2.8 hours at the second and subsequent infusions.
In her discussion of the study, Faith Davies, MD, MBBCh, MRCP, FRCPath, of Perlmutter Cancer Center at NYU Langone, commented that the data from this trial, which have been long awaited, did not disappoint.
“The shorter infusion time is very important for our health care systems,” she said. “A 3-hour and 2.8-hour infusion time is going to make a big difference to our clinical environment.”