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<sup>-4</sup> sensitivity threshold for ALL and 10<sup>-3</sup> 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]).

Authors

Institutions

Publication Details

Journal
HemaSphere
Published
2025-10-01
DOI
https://doi.org/10.1002/hem3.70245
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Óscar González‐Llano, André Baruchel, Daniel Freigeiro, C. Michel Zwaan et al.
HemaSphere
Acute Lymphoblastic Leukemia research
article

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

Óscar González‐Llano, André Baruchel, Daniel Freigeiro, C. Michel Zwaan, Lynn Wang, Simone Cesaro, Ana Virgínia Lopes de Sousa, Jochen Buechner, Guy Leverger, Corina Oprea, Sidnei Epelman, Ximo Duarte, Antonis Kattamis, Carmelo Rizzari, Arlet Alarcon, Jonas Abrahamsson, Elvis Terci Valera, Brigitte Nelken, Franca Fagioli, Sandrine Macé, LBP Moreira, Mariana Bohns Michalowski, Karsten Nysom, Hyoung Jin Kang, Giovanni Abbadessa, Willy Quiñones Choque, Marı́a Sara Felice
article en

Abstract

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<sup>-4</sup> sensitivity threshold for ALL and 10<sup>-3</sup> 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]).

HemaSphereVol. 9(10)
Oslo University Hospital (NO), Inserm (FR), Universidad Autónoma de Nuevo León (MX), National and Kapodistrian University of Athens (GR), Université Paris Cité (FR), Garrahan Hospital (AR), Sahlgrenska University Hospital (SE), Copenhagen University Hospital (DK), Rigshospitalet (DK), Seoul National University Hospital (KR), Sanofi (France) (FR), Centre Hospitalier Universitaire de Lille (FR), Sorbonne Université (FR), AVEO Oncology (United States) (US), Hôpital Armand-Trousseau (FR), Azienda Ospedaliera Universitaria Integrata Verona (IT), Support group for adolescents and children with cancer (BR), Hospital de Clínicas de Porto Alegre (BR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Jeanne de Flandre (FR), Seoul National University Children's Hospital (KR), IPO Porto (PT), Hospital Amaral Carvalho (BR), Hôpital Robert-Debré (FR), Princess Máxima Center (NL), Universidad Católica San Pablo (PE), Centre de Recherche Saint-Antoine (FR), Ospedale Regina Margherita (IT), Erasmus MC - Sophia Children’s Hospital (NL), Hospital Santa Marcelina (BR), Clinics Hospital of Ribeirão Preto (BR), Hospital General de Niños Ricardo Gutierrez (AR), University of Milano-Bicocca (IT)
Openalex Percentile: Top 58%
Acute Lymphoblastic Leukemia research
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.