A phase II study of thalidomide and vinblastine for palliative patients with Hodgkin's lymphoma

Introduction: Patients with Hodgkin's Lymphoma (HL) who relapse or progress after primary therapy and subsequent high dose chemotherapy with autologous stem cell transplantation ( ASCT) cannot be cured with conventional treatment. We combined thalidomide (THAL), an agent with anti-angiogenic and immunomodulatory properties, with vinblastine, which is active after ASCT, to determine the objective response rate, improvement in B symptoms and toxicity in patients with refractory HD. Methods: Patients were eligible if they HD that progressed after chemotherapy and ASCT or had declined or were ineligible for curative therapy. Treatment consisted of THAL 200mg orally given daily. After 2 weeks, VBL 6mg IV was given weekly x 6 doses on an eight-week cycle. Response and toxicity assessment occurred following each cycle. Results: Eleven patients were enrolled, 1 progressed within 6 days of study enrollment and was subsequently treated with alternative palliative therapy and thus 11 patients are response evaluable and 10 are evaluable for toxicity. Patient characteristics: relapsed after ASCT: 7; median number of prior chemotherapy regimens: 3 (range 1-5); median time to progression post-ASCT: 7 months (range 2-29). Four patients had a partial response to treatment (response rate 36%); two patients had stable disease. B symptoms were present at enrollment in four patients and resolved completely on treatment in two patients. Five had disease progression within 3 months of starting treatment. The median duration of response was 9 months (range 0-22 months). Toxicity was mild and limited to grade 2 neuropathy in 6 patients and grade 2 or 3 neutropenia in 4 patients. Conclusions: In this small study in chemotherapy-refractory HL, THAL and VBL demonstrated encouraging activity with some durable responses and acceptable toxicity. These results suggest that chronic low dose chemotherapy combined with less toxic immunomodulatory or anti-angiogenic drugs warrants further study.