Clinical and hematological improvement in patients receiving liposome doxorubicin (Myocet) therapy for myelofibrosis with myeloid metaplasia (MMM)

Abstract

6593 Background: MMM is a chronic myeloproliferative disorder with bone marrow fibrosis, hepato-splenomegaly, extramedullary hematopoiesis,increase angiogenesis both in bone marrow and spleen. Myocet is a proprietary liposomal formulation of doxorubicin designed to enhance delivery of the drug to tumor cells and reduce side effects while maintaining equivalent anti-tumor efficacy. Liposomes are avidly removed from circulation by the macrophages of the RES or MPS and are taken up in the spleen, liver and bone marrow were show both a cytotoxic and antiangiogenic activity. Methods: We thus designed a phase II study for pts with MMM. The treatment program consisted of 25 mg total dose of Myocet given I.V. every two weeks for six months. Eligibility criteria included a histologically confirmed diagnosis, platelets ≥ 100 × 109/L, neutrophils ≥ 1 × 109/L, PS ≤ 2, LVEF > 45%, normal liver and renal function. Eight patients (median age, 66 years; range, 60–73) were enrolled to the trial. Median duration of disease prior to protocol treatment was 45 months (range, 24–144). All pts had received prior therapy for MMM, including thalidomide (37%) hydroxyurea (100%), interferon (25%), anagrelide (25%), erythropoietin (100%). 3 pts were RBC transfusion-dependent and 1 had severe constitutional symptoms. Baseline median (range) values for palpable spleen size, leukocyte count, platelet count, CD34 cell count, and serum lactate dehydrogenase (LDH) were: 10cm BCM (median, range 6 to 30), 8.5 × 109/L (3–36.2), 250 × 109/L (160–950), 151.1 × 106/L (1.9–3568), and 680 U/L (316–868), respectively. 8/8 pts had JAK2 V617F mutation. Results: 7/8 pts are evaluable (i.e., received six months of therapy), 1 pt discontinued for progression. Clinico-hematologic responses have been observed in 7/7 (100%) pts and were evaluated according to European Myelofibrosis Network criteria. These include CR in 1 pt, major response in 5/7 pts, minor response in one. The median time to response was 12 weeks (range, 4 to 18). Therapy has been well tolerated. Only a Grade 3 thrombocytopenia was seen. Conclusions: We conclude that Myocet has clinical activity in a subset of patients with myelofibrosis with an acceptable toxicity profile. No significant financial relationships to disclose.