Thalidomide and rituximab in Waldenstrom macroglobulinemia
- 1 December 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 112 (12), 4452-4457
- https://doi.org/10.1182/blood-2008-04-150854
Abstract
Thalidomide enhances rituximab-mediated, antibody-dependent, cell-mediated cytotoxicity. We therefore conducted a phase 2 study using thalidomide and rituximab in symptomatic Waldenstrom macroglobulinemia (WM) patients naive to either agent. Intended therapy consisted of daily thalidomide (200 mg for 2 weeks, then 400 mg for 50 weeks) and rituximab (375 mg/m2 per week) dosed on weeks 2 to 5 and 13 to 16. Twenty-five patients were enrolled, 20 of whom were untreated. Responses were complete response (n = 1), partial response (n = 15), and major response (n = 2), for overall and major response rate of 72% and 64%, respectively, on an intent-to-treat basis. Median serum IgM decreased from 3670 to 1590 mg/dL (P < .001), whereas median hematocrit rose from 33.0% to 37.6% (P = .004) at best response. Median time to progression for responders was 38 months. Peripheral neuropathy to thalidomide was the most common adverse event. Among 11 patients experiencing grade 2 or greater neuropathy, 10 resolved to grade 1 or less at a median of 6.7 months. Thalidomide in combination with rituximab is active and produces long-term responses in WM. Lower doses of thalidomide (ie, ≤ 200 mg/day) should be considered given the high frequency of treatment-related neuropathy in this patient population. This trial is registered at www.clinicaltrials.gov as #NCT00142116.Keywords
This publication has 35 references indexed in Scilit:
- A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's LymphomaClinical Cancer Research, 2006
- Update on treatment recommendations from the Third International Workshop on Waldenstrom's MacroglobulinemiaBlood, 2006
- Polymorphisms in FcγRIIIA (CD16) Receptor Expression Are Associated With Clinical Response to Rituximab in Waldenström’s MacroglobulinemiaJournal of Clinical Oncology, 2005
- Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemiaCancer, 2004
- Multicenter Phase 2 Trial of Rituximab for Waldenström Macroglobulinemia (WM): An Eastern Cooperative Oncology Group Study (E3A98)Leukemia & Lymphoma, 2004
- Phase I Studies of Interleukin (IL)-2 and Rituximab in B-Cell Non-Hodgkin’s LymphomaClinical Cancer Research, 2004
- Treatment of Waldenstrom's macroglobulinemia with single-agent thalidomide or with the combination of clarithromycin, thalidomide and dexamethasoneSeminars in Oncology, 2003
- Potential new therapeutics for Waldenstrom's macroglobulinemiaSeminars in Oncology, 2003
- Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's MacroglobulinemiaSeminars in Oncology, 2003
- Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's MacroglobulinemiaSeminars in Oncology, 2003