Isatuximab Plus Kd Regimen Demonstrates Impressive mPFS in Relapsed Multiple Myeloma

In the phase 3 IKEMA study, isatuximab added to carfilzomib and dexamethasone improved progression-free survival in patient with relapsed multiple myeloma.

Treatment with isatuximab (Sarclisa) in combination with carfilzomib (Kyprolis) and dexamethasone (Kd) achieved unprecedented progression-free survival (PFS) improvement vs Kd alone in patients with relapsed multiple myeloma receiving a proteasome inhibitor therapy, according to data from the phase 3 IKEMA clinical trial (NCT03275285).

The median PFS observed with isatuximab plus Kd was 35.7 months compared with 19.2 in the Kd-only arm (HR, 0.58; 95% CI, 25.8-44.0). These findings represent the longest median PFS observed in a study of a proteasome inhibitor backbone administered to patients with relapsed multiple myeloma in the second-line setting.

“The increase in progression-free survival, observed consistently across all subgroups, when adding Sarclisa to carfilzomib and dexamethasone is remarkable in patients with relapsed multiple myeloma in a proteasome inhibitor combination. Relapse is common in multiple myeloma, creating the need for differentiated second-line treatments that provide patients a longer period of time without disease progression, said Philippe Moreau, MD, head of the Department of Hematology, University Hospital of Nantes, France, in a press release. “This updated analysis reinforces the potential for Sarclisa to become a new standard of care for patients with relapsed multiple myeloma.”

IKEMA is a randomized, open-label, multicenter study during which 302 patients are assigned to receive isatuximab via intravenous (IV) infusion on days 1, 8, 15, and 22 of first cycle, then on days 1 and 15 of subsequent cycles in combination with IV carfilzomib on day 1, 2, 8, 9, 15 and 16 plus IV or oral dexamethasone on day 1, 2, 8, 9, 15, 16, 22 and 23 of a 28-day cycle in the experimental arm, or matching dosing of Kd in the control arm.

In addition to PFS, the study investigated overall response rate, rate of very good partial response (VGPR) or better, complete response rate, and rate of VGPR or better with MRD, overall survival, time to response, PFS2, and duration of response as secondary efficacy end points. Other secondary end points of the study included the number of patients with adverse events, patient-reported outcomes, pharmacokinetics, and immunogenicity.

Patients enrolled were those with multiple myeloma previously treated with prior 1 to 3 lines and with measurable serum M-protein. Patients are required to be at least 18 years of age with an ECOG performance score of 2 or lower, measurable disease, and adequate biological tests. The study protocol excludes patients who received prior carfilzomib, those who never achieved at least 1 minor response during previous therapies, and/or those who did not respond to their last previous therapy completed within 14 last days. In addition, patients with certain comorbidities that may interfere with any of the agents in the study were excluded.

Following recommendations in censoring rules from the FDA, isatuximab plus Kd showed a median PFS of 41.7 months compared to 20.8 months in patients treated with Kd alone (HR, 0.59; 95% CI: 27.1 to not calculable [NC]) in a PFS analysis.

Results from the IKEMA study also showed time to next treatment, which was 44.9 months in the experimental arm compared with 25 months in the Kd arm (HR 0.55,m 95% CI, 31.6 to NC). The end point measures the period of therapeutic benefit for either combination.

“To observe progression-free survival of more than 3 years in patients with relapsed multiple myeloma when Sarclisa was added to a proteasome inhibitor backbone of therapy is unprecedented and reinforces our confidence in Sarclisa as a potential best in class anti-CD38 antibody, said Peter C. Adamson, MD, global head of Oncology Clinical Development and Pediatric Innovation at Sanofi, in a statement.

REFERENCES:

1. Sarclisa® (isatuximab) combination provides unprecedented median progression free survival in patients with relapsed multiple myeloma receiving a proteasome inhibitor therapy. News release. Sanofi. May 15, 2022. Accessed May 17, 2022. https://bit.ly/3NnjNW2

2. Multinational clinical study comparing isatuximab, carfilzomib and dexamethasone to carfilzomib and dexamethasone in relapse and/or refractory multiple myeloma patients (IKEMA). Clinicaltrials.gov. Updated May 12, 2022. Accessed May 18, 2022. https://bit.ly/3a7U7P8