Single‐dose (4.5 mg/m²) gemtuzumab ozogamicin in combination with fludarabine, cytarabine and anthracycline as reinduction therapy in relapsed or refractory paediatric acute myeloid leukaemia

Abstract

Summary Despite major therapeutic improvements, children with relapsed/refractory Acute Myeloid Leukaemia still have poor outcomes and overall survival does not exceed 40%. New treatments are required to improve their outcome; Gemtuzumab ozogamicin (GO), an anti‐CD33 immunoconjugate antibody, is a potent cytotoxic agent whose efficacy has been demonstrated mainly in adults. The main objective of this retrospective multicentre study was to assess the outcome of children treated, between February 2008 and August 2019, with GO at a single 4.5 mg/m2 dose, in combination with Fludarabine, Cytarabine and antssshracyclines, in context of a first relapse (n = 26) or refractory disease (n = 3). The remission rate was 83% (24/29 children) and 20 children (69%) were allografted. With a median follow‐up of 1.2 years (range: 0.1–8), the overall survival was 49% (CI95% = 33; 72). Most common adverse event was febrile neutropenia with microbiological identification in 55% of cases. Veno‐occlusive disease occurred in 6 patients (21%), of which 5 subvened after bone marrow transplantation, and resolved within 2–32 days (median 10.5 days). Administration of GO in combination with FLA‐anthracyclines chemotherapy appears to be a good reinduction regimen for relapsed or refractory AML with a good safety profile. These results warrant larger prospective study.

Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas

“…Clinical trials on children with r/r AML treated with GO combined with cytarabine and another chemotherapeutic (fludarabine or anthracyclines or mitoxantrone or L-asparaginase) demonstrated higher severe infection rates (46.2–55%; ~9% with grade ≥3 catheter-related infections, ~10% with IFDs, and ~10% with viral infections including SARS-CoV-2 and HSV) and rates of febrile neutropenia (28.9–84.6%), but fatal infections did not exceed 4.4% in all cohorts and corresponded primarily to Gram-negative sepsis [ 73 , 74 , 75 ]. Moreover, GO in combination with busulfan and cyclophosphamide as a myeloablative conditioning regimen prior to allo-HSCT has been associated with bloodstream bacterial infections in 41.7% of patients and sepsis in 25% [ 76 ].…”

Gemtuzumab Ozogamicin Monotherapy Is a Well-tolerated Palliative Chemotherapy Option in Pediatric Multiply Relapsed Acute Myeloid Leukemia: A Multicenter Case Series and Review of the Literature

“…Fourteen of 17 patients who received GO alone had a reduction in their MRD, and 13 became negative 3 . Twenty-eight of 29 patients who had GO with chemotherapy had a reduction in their MRD, and 13 became negative 5 . In Parigger and colleagues’ 22 review of GO use in pediatric AML, a median remission rate of 33% (range 17% to 100%) with GO monotherapy was reported.…”

“…3 Twenty-eight of 29 patients who had GO with chemotherapy had a reduction in their MRD, and 13 became negative. 5 In Parigger and colleagues' 22 review of GO use in pediatric AML, a median remission rate of 33% (range 17% to 100%) with GO monotherapy was reported. A 2020 case series of pediatric AML in the first relapse showed 6/8 patients attainted CR with 1 to 2 cycles of fractionated GO (3 mg/m 2 on days 1, 4, 7) combined with fludarabine/HD-ARAC followed by second HSCT.…”

“…New optimized therapeutic avenues for refractory/relapsed disease are yet to be discovered. In fact, OS of children with relapsed AML remains poor at 40% 4,5 . When curative intent treatments are no longer possible, palliative chemotherapy is often considered to prolong life, while optimizing patients’ quality of life and respect for their wishes.…”

“…In fact, OS of children with relapsed AML remains poor at 40%. 4,5 When curative intent treatments are no longer possible, palliative chemotherapy is often considered to prolong life, while optimizing patients' quality of life and respect for their wishes. In this review, we report 4 cases of multiply relapsed pediatric AML patients who were treated with gemtuzumab ozogamicin (GO) monotherapy with palliative intent.…”