IRAKLIA
Trial question
Is isatuximab on-body delivery system noninferior to intravenous isatuximab in patients with relapsed or refractory multiple myeloma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
45.0% female
55.0% male
N = 531
531 patients (238 female, 293 male).
Inclusion criteria: adult patients with relapsed or refractory multiple myeloma.
Key exclusion criteria: primary refractory multiple myeloma; treatment with anti-CD38 in the past 9 months; prior pomalidomide therapy; significant cardiac dysfunction; concomitant plasma cell leukemia; active primary amyloid light chain amyloidosis.
Interventions
N=263 isatuximab on-body delivery (at a dose of 1,400 mg weekly in cycle 1, then every 2 weeks plus pomalidomide 4 mg daily and dexamethasone 40 mg weekly).
N=268 intravenous isatuximab (at a dose of 10 mg/kg weekly in cycle 1, then every 2 weeks plus pomalidomide 4 mg daily and dexamethasone 40 mg weekly).
Primary outcome
Overall response rate at 12 months
71.1%
70.5%
71.1 %
53.3 %
35.5 %
17.8 %
0.0 %
Isatuximab on-body
delivery
Intravenous
isatuximab
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in overall response rate at 12 months (71.1% vs. 70.5%; RR 1.008, 95% CI 0.9 to 1.13).
Secondary outcomes
No significant difference in mean C6D1 predose (499 mcg/mL vs. 340 mcg/mL; GMR 1.532, 95% CI 0 to 3.07).
No significant difference in very good partial response or better rates (46.4% vs. 45.9%; RR 1.011, 95% CI 0.84 to 1.22).
No significant difference in progression-free survival at 12 months (66.1% vs. 65.1%; HR 1.015, 95% CI 0.75 to 1.38).
Safety outcomes
No significant difference in adverse events leading to treatment discontinuation.
Conclusion
In adult patients with relapsed or refractory multiple myeloma, isatuximab on-body delivery was noninferior to intravenous isatuximab with respect to overall response rate at 12 months.
Reference
Sikander Ailawadhi, Ivan Špička, Andrew Spencer et al. Isatuximab Subcutaneous by On-Body Delivery System vs Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed / Refractory Multiple Myeloma: Phase 3 IRAKLIA Study. J Clin Oncol. 2025 Jun 3:101200JCO2500744. Online ahead of print.
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