Gemtuzumab ozogamicin in children with relapsed or refractory acute myeloid leukemia: a report by Berlin-Frankfurt-Münster study group

Haematologica. 2019 Jan;104(1):120-127. doi: 10.3324/haematol.2018.191841. Epub 2018 Aug 9.

Abstract

Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia (AML) have poor survival. We evaluated gemtuzumab ozogamicin (CD33-targeted drug) used on a compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia Berlin-Frankfurt-Münster studies, and identified 76 patients (<18 years) with highly-advanced and pre-treated AML [refractory de novo acute myeloid leukemia (n=10), de novo AML refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary AML (n=5)]. At doses of 2.5-10 mg/m2, gemtuzumab ozogamicin was administered in 1-4 cycles as single agent (47%), combined with cytarabine (47%), or others (6%). Most common grade 3/4 adverse events were infections or febrile neutropenia (78% of severe adverse events), infusion-related immunological reactions (6%), and gastrointestinal symptoms (5%). Three patients experienced veno-occlusive disease (one fatal due to exacerbation of a pre-existing cardiomyopathy). Sixty-four percent received subsequent hematopoietic stem cell transplantation. Probability of 4-year overall survival was 18±5% in all, 27±7% in patients with and 0% in patients without hematopoietic stem cell transplantation (P<0.0001). Administration of gemtuzumab ozogamicin on a patient-specific, compassionate use basis was frequently considered in our study group and proved to be effective for bridging children with very advanced AML to hematopoietic stem cell transplantation. Uniform prospective studies for these patients are urgently needed.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Child
  • Disease-Free Survival
  • Female
  • Gemtuzumab / administration & dosage*
  • Gemtuzumab / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Survival Rate
  • Time Factors

Substances

  • Gemtuzumab