Interim Analysis of a Post Marketing All Cases Surveillance Study of Mylotarg in Japan.

A post marketing all cases surveillance study of Mylotarg in Japan was initiated to assess safety and efficacy in routine practice. The primary objectives of this registry are to estimate the incidences of adverse events, determine factors that could affect safety or efficacy, estimate the incidence of veno-occlusive disease (VOD), and investigate factors that could affect occurrence of VOD. Secondary objectives are to collect and report incidences of infections, hemorrhage, infusion reaction (including anaphylactic reaction), lung disorder, tumor lysis syndrome (TLS), and relapse-free survival and survival time. Survey forms were collected from 316 of the 737 registered patients treated with Mylotarg from May, 2005 to May, 2007. The majority of patients received 2 doses of 9 mg/m² Mylotarg at 2 weeks intervals. All 316 patients were included in the safety evaluation, and 229 patients were included in the efficacy evaluation. This interim analysis report summarizes the safety results of the survey conducted through May 16, 2007. 128 (40.5%) were female and 188 (59.5%) male. The median age of patients was 64 years, ranging from 1 to 90 years. 214 (67.7%) were in relapse and 99 (31.3%) were refractory. The distribution of patients by FAB classification (n = 288) was as follows: M0 (22), M1 (43), M2 (137), M3 (13), M4 (36), M5 (22), M6 (10) and M7 (5). The incidence of adverse reactions was 88.0%(grade 3 or higher = 76.6%) in the 316 patients. Serious adverse events included febrile neutropenia (n = 98), decreased platelet count (93), decreased WBC (58), decreased neutrophil count (52), anaemia (31), sepsis (30), pyrexia (20), pneumonia (17), thrombocytopenia (16), hypokalaemia (15), neutropenia (13), VOD (12), decreased haemoglobin (11), TLS (10) and disseminated intravascular coagulopathy (DIC, 10). In total, eleven pulmonary events were reported. The overall incidence of adverse events involving liver was 33.9%(grade 3 or higher = 12.0%). Factors affecting adverse events included age, pre-treatment PS, recurrence, complications (hepatic impairment, renal impairment, lung disorders, infections, heart disease), past treatment (frequency of remission induction chemotherapy, history of HSCT), frequency of dosing and total dosage with Mylotarg. The incidence of all VOD cases was 4.4% (14/316). There was a non-statistically significant difference (p=0.06) for the incidence of VOD in patients who underwent HSCT (9.1% for 5/55) compared to those that never had HSCT (3.5% for 9/261). Factors identified to possibly affect the onset of VOD were age, complications (hepatic impairment, infections), history of graft versus host disease, and pre-treatment HSCT. The incidence of infusion reactions in this survey was 46.5% (grade 3 or higher = 24.4%). Major infusion reactions that occurred in at least 10 patients were pyrexia (67), chills (26), platelet count decrease (14), DIC (13), anaemia (12), and TLS (10). In general, the safety profile for patients enrolled in this survey and analyzed in this interim analysis is consistent with that seen in the pivotal phase 2 clinical trials and reported in the literature.