MMM is a chronic myeloproliferative disorder accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis.

The molecular pathogenesis of MMM has not been fully characterized despite the recent discovery of an activating JAK2 mutation (JAK2V617F) in approximately half of the patients. Conventional drug therapy in MMM not improves survival and is used for palliative purposes only.

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.

Moreover 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 anti-angiogenic activity

We thus designed a phase II study for patients with primary MMM. The treatment program consisted of 25 mg total dose of Myocet™ given I.V. every two weeks for six months. Study eligibility criteria included a histologically confirmed diagnosis of MMM, platelet count ≥ 100 × 109/L, and neutrophil count ≥ 1 × 109/L, PS ≤ 2, LVEF > 50%, normal liver and renal function.

8 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 (100%) had received prior therapy for MMM, including thalidomide 3 (37%), hydroxyurea 8 (100%), interferon 2 (25%)), anagrelide 2 (25%), and erythropoietin 8 (100%). 3 patients (37%) were RBC transfusion-dependent and 1 had severe constitutional symptoms (night sweats or disease related fever).

Baseline median (range) values for palpable spleen size, leukocyte count, platelet count, CD34 cell count, and serum lactate dehydrogenase (LDH) were 10 cm BCM (median, range 6 to 30), 8.5 × 109/L (3–36.2), 250 × 109/L (160–950), 151.1 × 106/L (1.9–356), and 680 U/L (316–868), respectively. 8/8 pts had JAK2 V617F mutation. In addition, pre-treatment and post-treatment quantitative assessment by real-time quantitative polymerase chain reaction (RQ-PCR) of WT1 transcripts in the peripheral blood were performed and the values were expressed as WT1 copies every 104 copies of ABL. 7/8 pts are evaluable for response and toxicity (i.e., received six months of therapy) 1 pt discontinued because of progression.

Clinico-hematologic responses have been observed in 7/7 (100%) pts and were evaluated according to European Myelofibrosis Network criteria These include 1 CR, 5 Major Response,1 Minor Response

1 of 3 transfusion-dependent pts have become transfusion independent. The median time to response was 12 weeks (range, 4 to 18). Therapy has been well tolerated. Only a Grade 3 thrombocytopenia was seen.

Striking WT1 gene expression levels in samples that were obtained after treatment were found to be significantly lower (median 480 range 210–520) than those before (median 1000, range 560–1230) (P < .0001, Mann-Whitney U test) The median post-treatment follow up at the time of this writing was 10 months (range 8–13)

We conclude that Myocet has clinical activity in a subset of patients with myelofibrosis with an acceptable toxicity profile.

Disclosure: No relevant conflicts of interest to declare.

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