High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group

Abstract

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m 2 on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m 2 on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia o500/ll and thrombocytopenia o50 000/ll were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.

Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML)

“…Both, the median time to recovery of ANC >0.5 3 10 9 /L and blood platelets >50 3 10 9 /L was 27 days and thus comparable to literature data [10,19,26]. During myelosuppression, in almost all patients (88%) neutropenic fever emerged and four patients (17%) subsequently died due to infectious complications.…”

“…In the literature, many studies on GO-based therapies have been reported. Using GO as a single agent therapy in patients with refractory or relapsed AML, CR was achieved in 13-26%, leading to a median OS of 4.9 to 12 months [10,21,[25][26][27]. As a single agent, GO more likely induced a second CR than high dose araC especially in older patients with early relapse [28].…”

Gemtuzumab ozogamicin in combination with vorinostat and azacitidine in older patients with relapsed or refractory acute myeloid leukemia: a phase I/II study

“…GO at 3 mg/m 2 given on Days 1, 4 and 7) has been pioneered by the French ALFA group and revealed a favorable efficacy/toxicity profile. [22][23][24] For example, among 57 patients with AML in first relapse, GO monotherapy given in fractionated doses resulted in 15 (26%) CRs and 4 (7%) CRs with incomplete platelet recovery (CRps). Interestingly, relative to our study, the study by Taksin et al included adults of all ages requiring therapy for AML in first relapse with a CR duration of at least three and up to 18 months, 22 i.e.…”

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

“…The median RFS was 11 months in both the group of patients, CR and CRp. No major liver toxicities were observed and the authors concluded that GO administered in fractioned doses showed an excellent efficacy/safety profile (Taksin et al, 2007).…”