Isatuximab Shows Efficacy, Acceptable Safety Across Multiple Myeloma Trials

Efficacy data revealed that among 167 patients treated with isatuximab monotherapy, the objective response rate was 26.3% after a median follow-up of 4.5 months and included 44 responders.

Isatuximab-irfc (Sarclisa) as a single agent exhibited efficacy and an acceptable safety profile as a treatment for patients with relapsed/refractory multiple myeloma, according to results from a pooled analysis of phase 1 and 2 clinical trials published in Annals of Hematology.

Efficacy data revealed that among 167 patients treated with isatuximab monotherapy, the objective response rate (ORR) was 26.3% (95% CI, 19.8%-33.7%) after a median follow-up of 4.5 months (range, 0.0-29.8) and included 44 responders. An additional 32 patients experienced a minimal response, and 54 had stable disease.

The median time to response was 1.0 month (range, 0.9-9.1), and the median duration of response (DOR) was 10.3 months (95% CI, 8.28-27.86). Furthermore, the very good partial response rate was 11.4% (95% CI, 7.0%-17.2%), with a clinical benefit rate (CBR) of 44.3% (95% CI, 36.6%-52.2%).

The median progression-free survival (PFS) among this patient group was 5.6 months (95% CI, 3.9-7.2), and the median overall survival (OS) was 20.2 months (95% CI, 16.5-not reached [NR]). A multivariate analysis showed that International Staging System (ISS) stage III, high cytogenetic risk, and plasmacytomas at baseline were significantly negatively associated with PFS. Additionally, age, ECOG performance status, ISS stage, and baseline estimated glomerular filtration rate were significantly associated with OS outcomes.

Additionally, a subgroup analysis for PFS showed no difference among patients with or without clinical progression at baseline (HR, 0.72; 95% CI, 0.48-1.08). A similar trend was observed for OS (HR, 0.84; 95% CI, 0.513-1.377).

“The results [from the pooled analysis] show that isatuximab as monotherapy was efficacious in the treatment of individuals with [relapsed/refractory multiple myeloma] and that isatuximab had an acceptable safety profile when used alone and in combination with dexamethasone,” lead author Meletios Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Athens, Greece, wrote in the publication with study coinvestigators. “Therefore, adding isatuximab to existing [relapsed/refractory multiple myeloma] treatment regimens may improve outcomes, particularly in those who have been heavily pretreated, are refractory to a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD], and even in individuals [75 years and older] presenting with an ECOG [performance status] of 2.”

Patients with relapsed/refractory multiple myeloma who participated in the phase 1/2 TED10893 (NCT01084252) and TED14095 (NCT02812706) trials were included in the pooled efficacy analysis. The analysis was restricted to patients who received 20 mg/kg of weekly or biweekly isatuximab and whose treatment responses were confirmed by Independent Review Committee (IRC) assessment.

The safety analysis encompassed data from the TED10893 and TED14095 trials, as well as the phase 1 TED14154 (NCT02514668) trial and the phase 1/2 TCD14906 trial (NCT03194867). In this analysis, 2 treatment groups were assessed: those who were treated with isatuximab monotherapy, and those who were treated with isatuximab plus dexamethasone.

Among patients in the efficacy analysis, the median age was 68.0 years (range, 37-85), and 21.0% of patients were 75 years of age and older. A total of 49.1% of patients in this group were male, and 47.3% had an ECOG performance status of 1 vs 43.7% with an ECOG performance status of 0. The mean body weight among patients was 70.6 kg (SD, 16.6), and 75.4% of patients had a renal response status of 50 mL/min/1.73m² or greater at baseline.

Furthermore, among those in the safety analysis (n = 477), the median age was 66.0 years (range, 37-85), with 17.0% of patients being 75 years of age and older. A total of 53.5% of this group were male, and the mean weight was 75.25 kg (SD, 19.72). Additionally, 56.6% of this patient group had an ECOG performance status of 1, 35.0% had ISS stage II disease, and 23.7% had confirmed high-risk cytogenetics. Most patients had mild (38.8%) or moderate impairment (29.4%) of renal function and were treated with a median number of 4.0 (range, 1-14) lines of therapy.

The efficacy end points of the pooled analysis included ORR, CBR, clinical progression status, PFS, OS, and DOR. Safety end points included incidence of treatment-emergent adverse effects (TEAEs), infusion reactions, respiratory TEAEs, hematologic AEs, and infections.

Among patients evaluable for safety, any-grade TEAEs occurred in 95.0%, with grade 3 or higher TEAEs occurring in 54.5%. The incidences of any-grade and grade 3 or higher TEAEs were similar across dose groups. The most common TEAEs by preferred term included infusion-related reactions (45.7%), fatigue (23.5%), diarrhea (20.3%), nausea (18.0%), and upper respiratory tract infection (18.0%). Common grade 3 or higher TEAEs by preferred term included anemia (11.9%), pneumonia (7.5%), thrombocytopenia (5.7%), disease progression (4.2%), and neutropenia (3.4%).

Reference

Dimopoulos M, Sunami K, Leleu X, et al. Efficacy and safety of isatuximab monotherapy to treat relapsed or refractory multiple myeloma: a pooled analysis of clinical trials. Ann Hematol. 2025;104;2337-2350. doi:10.1007/s00277-025-06343-9