Clinical Results in Patients with Primary and Secondary Myelofibrosis Treated with Monthly Cycles of Oral Melphalan.

Abstract 4985

Prolonged continuous oral Melphalan treatment was successfully employed in patients with Idiopathic Myelofibrosis (IM); however, a high incidence of evolution into blastic phase (BP) was observed. In order to reduce the incidence of BP and other side effects, a different Melphalan schedule with intermittent monthly cycles was tested at our Institution. From 1/2003 to 2/2009, 24 patients (16 males and 8 females, median age 66.2 years, range 41.7 – 76.2) were enrolled into the study; 19/24 had primary IM while in 5 there was a previous history of Polycythemia Vera/Essential Thrombocythemia. Six patients (25%) had been pretreated with Hydroxyurea. A symptomatic splenomegaly was present in all patients, with median spleen enlargement below costal margin of 12 cm (range 7 – 22). Median WBC level was 11.6 × 10⁹/l (range 3.6 – 63.6), with 11/24 patients having WBC > 12.0 × 10⁹/l; in addition, 3 patients had PLT level > 500 × 10⁹/l, 11 patients Hb level < 10 g/dl and 3 patients had transfusional requirement. Melphalan was administered orally at the dose of 8 mg/day for 5 consecutive days every month. Twelve patients (50%) had a reduction of spleen enlargement > 75%, 2 patients > 50% and 1 patient > 25%, with a global response rate of 15/24 patients (62.5%): the remaining 9 patients had no variation in spleen volume. Elevated WBC values reduced to normal in all but one patient, elevated PLT values reduced to normal in 2 out of 3 patients, transfusional requirement disappeared in 1 out of 3 patients. Median number of cycles to best response was 10 (range 2 – 30). As concerns hematological toxicity, 4 patients had Hb decrease < 8 g/dl, with 3/4 requiring transient transfusional support, and 1 patient had PLT decrease to < 50 × 10⁹/l. One patient resistant to treatment died from broncopneumonia and 1 patient with normal PLT values died from cerebral hemorrhage; two patients had a grade 3 – 4 gastro-intestinal hemorrhage. Interestingly, only 2/24 patients (8.3%) had a BP evolution after 8 and 16 months from start of Melphalan, respectively. After a median number of treatment cycles of 18 (range 2 – 68), 12 patients are still in therapy and 12 discontinued Melphalan due to toxicity (4), resistance (3), relapse (3) or evolution to BP (2). In conclusion, the intermittent cyclic schedule of oral Melphalan seems capable to maintain a good response rate with reduction of symptomatic spleen enlargement in more than 50% of patients without excessive toxicity and with a lower rate of BP evolution, as compared to continuous Melphalan administration.