Abstract
Abstract 4123
There is no effective therapy for primary myelofibrosis (MF) and post- essential thrombocythemia/polycythemia vera MF (ET/PV-MF) and conventional therapies are only palliative. Allogeneic stem cell transplantation which is the only curative option carries high mortality and morbidity and is precluded by age, poor performance status and co-morbidities. IMiDs like thalidomide and lenalidomide have been used with prednisone with some degree of response but the high doses used cause significant side effects. Single agent interferon use has in myelofibrosis has been disappointing and limited by toxicity at higher doses while low dose interferon has not been combined with other drugs. We used a unique combination of low doses of thalidomide (50 mg/day) along and prednisone (20 mg every other day) and IFN-a (1.5 million units three times a week) for patients with myelofibrosis.
Subjects: A single institution retrospective review was carried out in 8 patients with primary or post-ET/PV MF. All patients had a baseline hemoglobin <10g/dl or were RBC-transfusion dependent (1 transfusion in 8 weeks prior to treatment). Any prior therapy was discontinues for at least 2 weeks prior to treatment. Patients were required to have adequate hepatic, renal function, ANC >1000/l, and platelets >100,000/l prior to starting therapy. Patients were started on thalidomide, prednisone orally, and IFN-a subcutaneously three times a week. Therapy was continued until there was progressive disease. At any time during the treatment phase, in case of unacceptable toxicity from thalidomide, patients were switched to low dose lenalidomide, 5 mg a day by mouth. Response assessments were based on the International Working group for Myelofibrosis research and treatment (IWG-MRT) criteria. Applicable responses under clinical improvements category for anemia included an increase in hemoglobin >2g/dl above baseline or RBC transfusion independence and for splenomegaly included a 50% reduction in the palpable component of spleen for 2 or more months.
We report results with a follow-up of 5.25 years from start of treatment. 1 patient discontinued therapy after 4 months due to progressive disease. Out of remaining 7 patients, 6 patients (85.7%) showed clinical improvement. 1 patient is still continuing on thalidomide combination at 5.25 years with clinical improvement. 1 patient who achieved CR was switched from thalidomide to lenalidomide after 1 year of therapy due to neurotoxicity and shows clinical improvement at 5 years from start of treatment. No grade 3–4 toxicity was seen in any patients. Improvement in anemia was seen in 6 out of 7 patients (85.7%). Major reductions in spleen size were seen in 3 out of 7 patients (43%). Median time form start of treatment to response was 1 month. Serial bone marrow analyses are available in 2 patients showing substantial decrease in fibrosis.
The novel combination of low dose thalidomide, prednisone, and IFN-a results in durable and prolonged clinical response and is extremely tolerable with low toxicity. This promising combination should be explored further to offer treatment options to patients with myelofibrosis where currently there is no effective therapy.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
