Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

Abstract

Gemtuzumab ozogamicin, an anti-tumour antibiotic linked to an anti-CD33 antibody (Mylotarg®), has been well studied in AML in adults but to a lesser extent in children. No review has yet been published on the dose-related toxicity and efficacy of gemtuzumab ozogamicin in pediatric AML patients. Here we looked at 14 studies then scatterplots and linear regressions were used to estimate the relationship between the dose of gemtuzumab and its toxicity and efficacy. A nonsignificant increase in bilirubin level and in incidence of veno-occlusive disease was seen with higher doses of gemtuzumab ozogamicin when used as single-agent. In terms of efficacy, even a low dose of 3 mg/m 2 of gemtuzumab ozogamicin can have antileukemic effect, but available data do not allow conclusions on its dose-dependency. Data indicate that higher doses of gemtuzumab ozogamicin account for more adverse events. The data do not show that a high dose is required for anti-leukemic efficacy of gemtuzumab ozogamicin. This study also indicates that there seems to be a role for gemtuzumab ozogamicin in the treatment of pediatric AML and further studies are required to assess its optimal dose, schedule and balance between efficacy and side-effects. ARTICLE HISTORY

Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel

“…In children, GO has been used in non‐APL AML with encouraging results, as recently reviewed by Parigger et al (). Further, GO induced a sustained molecular CR in combination with ATO in a child with multiply relapsed APL (Inoue et al , ).…”

Strategies for reducing the treatment‐related physical burden of childhood acute myeloid leukaemia – a review

“…However, SOS has also been reported in less than 1% of children not treated with GO-containing chemotherapy (Gamis et al, 2014). The risk of GO-induced SOS seems related to the dose of GO (Parigger et al, 2016). In children with newly diagnosed AML treated with chemotherapy plus GO at 3 mg/m 2 , SOS of any degree of severity was observed in less than 4%.…”

“…The efficacy of gemtuzumab ozogamicin is promising, but so far has not replaced the intensive use of anthracyclines (Parigger et al, 2016) but may give a survival benefit when added to conventional chemotherapy (Hills et al, 2014). Protocols without the anthracycline-cytarabine based induction, a combination that results in major side effects, have not been successful.…”

“…Protocols without the anthracycline-cytarabine based induction, a combination that results in major side effects, have not been successful. The efficacy of gemtuzumab ozogamicin is promising, but so far has not replaced the intensive use of anthracyclines (Parigger et al, 2016) but may give a survival benefit when added to conventional chemotherapy (Hills et al, 2014). The optimal consolidation is not defined including the role of allogeneic haematopoietic stem cell transplantation (HSCT).…”

Advances in the drug therapies of acute myeloid leukemia (except acute promyelocytic leukemia)

“…Unfortunately, results of an analysis indicated that higher doses of GO account for more adverse events. 65 …”