On March 2, 2020, the FDA approved isatuximab (Sarclisa) in combination with pomalidomide and dexamethasone for multiple myeloma patients with relapsed or refractory disease after at least two prior therapies. Approval was based upon a Phase 3 trial comparing IsaPomDex vs PomDex ( Attal et a Lancet. 2019 Dec 7;394(10214):2096-2107. . The study enrolled 307 patients: 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. Adverse events included: were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). There was no difference in fatal adverse events between groups.
This competes directly with daratumumab/pomalidomide/dexamethasone which was FDA approved based upon a Phase 2 trial Chari et al (Blood. 2017 Aug 24;130(8):974-981.; who showed comparable response rates and toxicities.
Now, how to decide which CD38 directed antibody to choose? The advantage for isatuximab is smaller infusion volume and shorter infusion duration. The projected FIRST year costs are less for isatuximab based on listed pricing and that there is only 4 weekly doses followed by every two weeks thereafter. However, beyond the first year, the cost advantage is less clear as the daratumumab goes to monthly administration on month 7 whereas the isatuximab continues every 2 weeks indefinitely. Further complicating the "which one should I prescribe" is that it likely that daratumumab, similar to rituximab, will be available in a subcutaneous formulation in the not too distant future: much lower infusion reactions and, obviously, much more rapid administration.