Safety and activity of the multikinase inhibitor sorafenib in heavily pretreated patients with refractory/relapsed malignant lymphomas: Final results of a phase II study.

Abstract

e13593 Background: Sorafenib might have a role in the treatment of malignant lymphomas by overcoming the cytoprotective effects of Bcl-XL, ERK, and Mcl-1 and eventually targeting additional signalling pathways relevant to lymphomagenesis. This Phase II study was aimed to determine safety and activity of Sorafenib in patients (pts) with refractory/relapsed malignant lymphomas. Methods: Between March 2008 and July 2010, 30 pts (M/F: 19/11; median age, 61 years; range, 18-74) with relapsed (n = 6) or refractory (n = 24) aggressive non-Hodgkin lymphoma (NHL) (n = 14), indolent NHL (n = 7), chronic lymphocytic leukemia (n = 2), peripheral T cell NHL (n = 1) and Hodgkin Lymphoma (n = 6) were enrolled in this study. Prior to study entry, pts received a median of 4 (range, 1-8) lines of treatment with autografting performed in 67% and an additional allografting in 17% of cases. Sorafenib 400 mg BID was administered continuously until disease progression or appearance of clinical significant toxicity. Tumor response was assessed according to the revised response criteria for malignant lymphoma. Results: Pts received a median of 4 months (mos) (range, 1 – 10) of therapy. Common grade 1-2 adverse events (AE) were diarrhea (27%), hand-foot skin reaction (HFSR) (23%), fatigue (23%), weight loss (17%), thrombocytopenia (36%) and anemia (10%); grade 3-4 AE included HFSR (20%), infection (12%), neutropenia (20%) and thrombocytopenia (14%). The overall response rate was 13%, 2 pts achieved complete remission, 2 pts partial remission; response duration (DR) was 7, 5, 7 and 3 mos. Stable disease (SD) was observed in 15 pts, progression disease (PD) in 11. 37% of pts with at least a SD had a DR > 5 mos. Median progression free survival was 4 mos (range, 1-9), median survival was 16 mos (range, 1-34). Analysis of phosphorylation of ERK (pERK) in peripheral blood lymphocytes showed significant difference in pre- and post-treatment values between responding and non responding pts. Conclusions: Sorafenib in lymphoma pts was well tolerated. Although objective reponse was limited, results suggest an antilymphoma activity that warrants further researches focused on combination therapy.