Isatuximab in combination with chemotherapy for pediatric patients with relapsed/refractory acute lymphoblastic...

Area of Science:

• Pediatric Oncology
• Hematology
• Immunotherapy

Background:

• Relapsed acute leukemia in children carries a poor prognosis, necessitating novel treatment strategies.
• Current therapies for relapsed leukemia are often toxic and may lack efficacy.
• Isatuximab, an anti-CD38 antibody, is approved for adult multiple myeloma, suggesting potential in other hematologic malignancies.

Purpose of the Study:

• To investigate the efficacy and safety of isatuximab combined with salvage chemotherapy in pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
• To evaluate the complete response (CR) rate, including CR with incomplete peripheral recovery (CRi), as the primary endpoint.
• To assess minimal residual disease (MRD) negativity and safety profiles.

Main Methods:

• The ISAKIDS study (NCT03860844) was a Phase 2, single-arm, multicenter, open-label trial.
• Pediatric patients (28 days to <18 years) received isatuximab induction followed by weekly doses, combined with standard salvage chemotherapy.
• Consolidation or optional second induction therapy was administered to responders.

Main Results:

• A combined CR/CRi rate of 54% (32/59) was observed across evaluable patients (B-ALL: 52%, T-ALL: 45%, AML: 61%).
• Minimal residual disease (MRD) negativity was achieved by 56% of CR/CRi patients.
• A fatal case of cytokine release syndrome occurred in a patient with high baseline white blood cell count, leading to trial adaptation; other toxicities were manageable.

Conclusions:

• While isatuximab showed initial efficacy in combination with intensive chemotherapy for pediatric relapsed leukemia, the CR/CRi rates did not meet the predefined criteria to advance to Stage 2 of the ISAKIDS study.
• The study highlights the need for careful patient selection and management of potential toxicities, such as cytokine release syndrome, when using novel immunotherapies in pediatric hematologic malignancies.
• Further research may be warranted to optimize isatuximab-based regimens or explore alternative therapeutic strategies for this challenging patient population.