Isatuximab in combination with chemotherapy for pediatric patients with relapsed/refractory acute lymphoblastic leukemia or acute myeloid leukemia: The ISAKIDS study.

Children with relapsed acute leukemia have a poor prognosis; current relapse treatments are toxic, and novel treatments are needed. The anti-CD38 antibody isatuximab is approved for relapsed-refractory multiple myeloma in adults. We present results of the ISAKIDS study (NCT03860844) investigating isatuximab in children with relapsed-refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). This Phase 2, single-arm, multicenter, open-label study enrolled children aged 28 days to <18 years. Patients received isatuximab 20 mg/kg induction on Day 1, then weekly for 5 weeks (ALL) or 3 weeks (AML). Standard salvage chemotherapy was added on Day 8. Participants showing possible response could receive consolidation with every-other-week isatuximab (two doses) plus chemotherapy (T-ALL, B-ALL) or optional second induction (AML). The primary endpoint was the complete response (CR) rate (proportion with CR or CR with incomplete peripheral recovery [CRi]). CR/CRi was observed for 32/59 (54%) evaluable patients (B-ALL, 13/25 [52%]; T-ALL, 5/11 [45%]; and AML, 14/23 [61%]). Secondary endpoints included minimal residual disease (MRD) status and safety. Based on local and central analysis, 56% (18/32) of CR/CRi patients reached MRD negativity using 10-4 sensitivity threshold for ALL and 10-3 sensitivity threshold for AML. One event of fatal cytokine release syndrome was reported in a patient with a high baseline white blood cell count, leading to trial adaptation. The toxicity of isatuximab with chemotherapy was otherwise manageable. Despite initial evidence of efficacy of isatuximab combined with intensive chemotherapy, CR/CRi rates did not meet stringent prespecified criteria to proceed to ISAKIDS Stage 2 (≥60% [T-ALL] and ≥70% [B-ALL and AML]).