Gemtuzumab Ozogamicin (Mylotarg^®) in Children with Refractory or Relapsed Acute Myeloid Leukemia

Abstract

Background: Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML. Patients and Method: We report 12 children with multiple relapsed or refractory AML receiving GO as compassionate use. 11 children had initially been treated according to the AML-BFM 93 or 98 protocol, 1 girl received relapse treatment (liposomal daunorubicin/FLAG) due to secondary AML. After relapse, 10 children received an intensive relapse therapy (AML-BFM 97 or international AML-Relapse Study 2001/01). 2 of them had been transplanted in first or second CR before GO therapy. Results: 5 of 12 children responded to treatment with blast reduction to below 5%, but no child achieved CR after GO. Time until reoccurrence of blasts in almost all children with GO response was 3–8 months. In 5 children stem cell transplantation (SCT) was performed after GO therapy. 4 of them suffered from further progression of AML, 1 boy is in second remission with a follow-up of 8 months. 2 children had severe side effects. An anaphylactic reaction with severe hypotension was managed by catecholamine support and intensive care. In 1 girl, who relapsed after SCT in first remission, a veno-occlusive disease of the liver occurred, but could be treated successfully with defibrotide. Conclusion: GO therapy can induce blast reduction in children who have no further conventional treatment options. Frequency and severity of adverse events are limited, and therapy seems to be feasible for children with a sufficient general condition. Controlled studies are necessary to learn more about efficacy and side effects, especially implications for further therapy.

Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia

“…Additionally, these results are similar to those of 2 published reports in which gemtuzumab ozogamicin was used to treat children with refractory/relapsed AML on a compassionate-use basis. 18,19 As reported by Zwaan et al, 18 15 children (4 with de novo disease, 11 with relapsed/refractory disease) were administered gemtuzumab ozogamicin in the dose range of 4 to 9 mg/m 2 per course. Clinical response included 3 patients achieving CR, 5 patients achieving CRp, and 3 patients with no change in bone marrow blast count.…”

“…15,16 Only limited data exist regarding the use of gemtuzumab ozogamicin for the treatment of refractory or relapsed AML in children. [17][18][19][20] This phase-1 clinical trial was undertaken to evaluate the efficacy and tolerability of gemtuzumab ozogamicin as monotherapy in children younger than 18 years of age with relapsed or refractory CD33 ϩ AML.…”

Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel

“…180 Salvage studies demonstrated that the drug was beneficial in children who had poor chances of survival by conventional therapy. 175,181,182 In adults, study MRC AML15 showed that GO was beneficial in those with favorable cytogenetics and in part of patients in the intermediate-risk group; however, there was no benefit to those in the adverse-risk group. 174 In addition, other recent international studies on adult AML (by the French and United Kingdom groups) confirmed a survival benefit for AML subgroups when GO was added to induction chemotherapy.…”

The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients

“…Five children presented a hematological improvement with a bone marrow blastic count lower than 5% without achieving a CR. Only one patient presented a VOD that recovered after defibrotide treatment (Reinhardt et al, 2004). In another series, 29 refractory or relapsed children received two doses of GO (separated by 2 weeks) at 6, 7.5 or 9 mg/m 2 .…”