Posted: Friday, September 15, 2023
Longer-term results of the randomized phase III IKEMA trial, published in Blood Cancer Journal, continue to support the addition of isatuximab, an anti-CD38 monoclonal antibody, to carfilzomib and dexamethasone as a standard-of-care treatment for patients with relapsed multiple myeloma (who have received one to three prior treatment lines). Thomas Martin, MD, of the University of California, San Francisco, and colleagues noted that their prespecified analyses addressed progression-free survival, the study’s primary endpoint; final complete response; measurable residual disease (MRD) negativity; and safety.
In the trial, 177 patients received isatuximab plus carfilzomib/dexamethasone, and 122 received carfilzomib/dexamethasone alone. With a median follow-up of 44 months, adding isatuximab prolonged progression-free survival, consistent with the primary interim analysis: median progression-free survival, 35.7 months with the combination versus 19.2 months with carfilzomib/dexamethasone alone. The hazard ratio of 0.58 corresponded to a 42% reduction in the risk of disease progression or death.
The median progression-free survival of nearly 3 years with the addition of isatuximab is “unprecedented,” according to the investigators. “[It is] the longest progression-free survival reported to date with a proteasome inhibitor–based regimen in the relapsed myeloma setting. The extent of such a progression-free survival benefit is in line with the current trend toward more intense therapy earlier in the course of the disease.”
Additionally, isatuximab plus carfilzomib/dexamethasone provided a progression-free survival benefit across subgroups, including patients those with a poor prognosis. The safety profile of the three-drug combination was also similar to that reported in the prior interim analysis.
The team found the stringent complete response/complete response rate was 44.1% with isatuximab and carfilzomib/dexamethasone versus 28.5% with carfilzomib/dexamethasone alone (odds ratio [OR] = 2.09). The MRD negativity rate was 33.5% versus 15.4% (OR = 2.78), and the MRD negativity complete response rate was 26.3% versus 12.2%.
Disclosure: The study authors’ disclosure information can be found at nature.com.