Phase II Study of Lenalidomide (CC-5013, Revlimid®) for Patients (pts) with Myelofibrosis (MF).

Introduction: Thalidomide has been shown to induce responses in pts with MF but prolonged administration in these pts may be associated with neurotoxicity and other adverse events. Lenalidomide is the lead clinical compound in a new group of drugs called IMiDs®, which have immunomodulatory properties. It affects cytokine expression 200–5000 times more potently than thalidomide but lacks the teratogenecity, sedation and neurotoxicity.

Methods: We thus designed a phase II study for pts with myelofibrosis (primary or associated with myeloproliferative disorders) with a platelet (plt) count of at least 30 x10⁹/L. Pts may have received prior therapies, but were excluded if they had known hypersensitivity to thalidomide. Pts received lenalidomide 10 mg/day orally (5 mg daily for patients with platelet count less than 100,000 at study entry).

Results: We have treated 41 pts. Their median age was 65 (range, 42 to 83). Thirty-six pts (88%) had received prior therapy for MF, including thalidomide 13 (32%), hydroxyurea 12 (29%), interferon 11 (27%) (pegylated 7), anagrelide 10 (24%), and erythropoietin 6 (15%). Baseline hemoglobin was <10g/dl in 19 (46%) (13, 32% transfusion dependent); platelets <100 x10⁹/L in 12 (29%); neutrophils <1.5 x10⁹/L in 2 (5%), and 20/34 (59%) had splenomegaly (median 10cm BCM, range 1 to 30) (7 prior splenectomy). Twenty pts are evaluable for response and toxicity (i.e., received at least 30 days of therapy, unless discontinued because of progression or toxicity). One pt discontinued therapy because of toxicity (grade 3 rash). Responses have been observed in 10 (50%) pts. These include CR in 2 pts (normalization of Hgb and WBC, respectively), PR in 2 pts (improvement in plts and hgb, ± spleen), hematologic improvement in 6 pts (improvement in plts 3, spleen 2, WBC 1). Three of 13 transfusion-dependent pts have become transfusion independent. The median time to response was 9 weeks (range, 2 to 22). Responses have been sustained for a median of 14 weeks (range, 2 to 28 weeks). Therapy has been well tolerated. The more common toxicities were rash in 12 (29%), and pruritus in 8 (20%). Grade ≥ 3 toxicities were thrombocytopenia (n=2), rash (n=1), fatigue (n=1), and neutropenia (n=1). Four (10%) pts have required dose reduction and 1 discontinued therapy because of toxicity (rash).

Conclusion: We conclude that lenalidomide has clinical activity in a subset of patients with myelofibrosis with an acceptable toxicity profile. Studies using lenalidomide in combination with other agents are justified.