Isatuximab triplet improves PFS in R/R MM

The triplet therapy of anti-CD38 isatuximab, carfilzomib, and dexamethasone gave a significant improvement in progression-free survival (PFS) versus carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma (R/R MM).

Prof. Philippe Moreau (University Hospital of Nantes, France) presented the interim results of the open-label phase 3 IKEMA study [1]. This study randomised 302 patients with R/R MM who had previously received 1 to 3 lines of therapy to receive either intravenous isatuximab at 10 mg/kg plus carfilzomib and dexamethasone (n=179) or carfilzomib/dexamethasone alone (n=123). Isatuximab was administered weekly for 4 weeks, and then every 2 weeks. Carfilzomib was administered at 20 mg/m² on the first 2 days and then 56 mg/m² twice-weekly thereafter for 3 to 4 weeks, followed by twice-weekly dexamethasone at 20 mg. Treatment was given until disease progression, unacceptable toxicity, or patient decision.

The primary endpoint was PFS as determined through log-rank testing by the independent review committee; the pre-specified efficacy significance was set at a P-value <0.005. Secondary outcome measures included objective response rate (ORR), very good partial response (VGPR) rate or better, complete response (CR) rate, minimal residual disease (MRD) negativity rate, and overall survival (OS). Safety was assessed via treatment-emergent adverse effects (TEAEs). The interim analysis was planned when 65% of the total expected PFS events were observed.

With median follow-up of 20.7 months, the median PFS was not reached in the isatuximab arm and was 19.15 months in the carfilzomib/dexamethasone arm (95% CI 15.77–not available), leading to a 47% reduction in the risk of disease progression or death (HR 0.531; 95% CI 0.318-0.889; P=0.0007). These data exceeded the prespecified significance, thus the primary endpoint was met. The PFS benefit was consistent across patient subgroups, “including patients who are difficult to treat, such as [those with] high-risk cytogenetics or elderly patients,” Prof. Moreau said.

Secondary outcomes varied. No difference was observed for the ORR, which was 86.6% with isatuximab versus 82.9% with carfilzomib/dexamethasone (P=0.19). However, VGPR rates were improved with isatuximab (72.6% vs 56.1%; P=0.0011). The CR rate was 39.7% for isatuximab versus 27.6% with carfilzomib/dexamethasone. Importantly the MRD negativity rate was 29.6% and 13.0% with the isatuximab and carfilzomib/dexamethasone-alone arms, respectively (P=0.0004). No difference in OS was reported at this time, but the data are still immature.

The rate of serious TEAEs was similar in both arms (59.3% for isatuximab vs 57.4% with carfilzomib/dexamethasone) as was the rate of fatal AEs (3.4% vs 3.3%, respectively). Fewer patients on isatuximab discontinued treatment due to disease progression (29.1%) compared with carfilzomib/dexamethasone (39.8%), while 8.4% and 13.8%, respectively, discontinued therapy due to AEs.

Prof. Moreau concluded that “isatuximab with [carfilzomib/dexamethasone] may represent a new standard of care for patients with relapsed multiple myeloma.”

1. Moreau P, et al. Isatuximab plus carfilzomib and dexamethasone vs carfilzomib and dexamethasone in relapsed/refractory multiple myeloma (IKEMA): interim analysis of a phase 3, randomized, open-label study. EHA25 Virtual, 11-21 June 2020, Abstract LB3603.

Posted on 9 September 202018 March 2024