Omacetaxine for CML

New Orleans—After at least 24 months of follow-up, heavily pretreated patients with chronic phase or accelerated phase chronic myeloid leukemia (CML) had clinically meaningful and durable responses to omacetaxine, according to a subset analysis of 2, phase 2, single-arm studies. All patients were resistant to or intolerant of tyrosine kinase inhibitors (TKIs).

Results were presented during a poster presentation at the ASH meeting. The poster was titled Final Analysis of the Efficacy and Tolerability of Subcutaneous Omacetaxine Mepesuccinate, ≥24 Months after First Dose, in Patients with Chronic Phase (CP) or Accelerated Phase (AP) Chronic Myeloid Leukemia (CML).

The authors mentioned that 20% to 30% of patients with CML are resistant to or intolerant of TKIs, while approximately 4% cannot tolerate imatinib, an oral FDA-approved drug to treat CML. Omacetaxine, a protein synthesis inhibitor administered subcutaneously, is FDA-approved for chronic phase and accelerated phase CML.

In this analysis, the authors included patients with chronic phase and accelerated phase CML who received at least 2 prior FDA-approved TKIs and had documented evidence of resistance or intolerance to dasatinib and/or nilotinib. Patients were eligible if they were at least 18 years of age, had Philadelphia chromosome-positive CML, and were ineligible for bone marrow transplantation at the time of enrollment. Exclusion criteria included class III or IV heart disease, active ischemia, any other uncontrolled cardiac condition, or myocardial infarction in the previous 12 weeks, uncontrolled and active infection, HIV, and another concurrent illness that would preclude study conduct and assessment.

Patients received 1.25 mg/m² of subcutaneous omacetaxine twice daily, 14 days for induction followed by 7 days as maintenance therapy after a response, in 28-day cycles. As of October 12, 2012, there were 111 patients: 76 had chronic phase disease and 35 had accelerated phase disease.

At 24 months, 18% of chronic phase patients had a major cytogenetic response. Among those patients, the mean time to onset was 3.5 months and the median duration was 12.5 months. The major hematologic response rate for chronic phase patients was 70%, while the median time to onset was 0.7 months and the median duration was 11.1 months. Meanwhile, 14% of patients in the accelerated phase group had a major hematologic response, with a median time to onset of 2.3 months and a median duration of 4.7 months. No patients with accelerated phase CML had a major cytogenetic response, and 9% had a minor cytogenetic response.

The median progression-free survival was 9.6 months for chronic phase patients and 3.6 months for accelerated phase patients. Median overall survival was 40.3 months and 14.3 months, respectively.

The following adverse events were found in at least 20% of chronic phase and accelerated phase patients: thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthma, and pyrexia. Leukopenia and headache were found in at least 20% of chronic phase patients, and febrile neutropenia was found in at least 20% of accelerated phase patients.

There were 53 deaths in the chronic phase group and 38 deaths in the accelerated phase group. In addition, 5 and 4 deaths, respectively, occurred during the study, while 48 and 34 deaths, respectively, occurred >30 days after the last dose.

This study was sponsored by ChemGenex Pharmaceuticals, a wholly owned subsidiary of Teva Branded Pharmaceutical Products R&D, Inc.