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/m(2) 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, Subject(s)
Antibodies, Monoclonal/administration & dosage
, Antineoplastic Combined Chemotherapy Protocols/therapeutic use
, Thalidomide/administration & dosage
, Waldenstrom Macroglobulinemia/drug therapy
, Adult
, Aged
, Aged, 80 and over
, Antibodies, Monoclonal/adverse effects
, Antibodies, Monoclonal, Murine-Derived
, Antineoplastic Combined Chemotherapy Protocols/adverse effects
, Disease-Free Survival
, Dose-Response Relationship, Drug
, Drug Administration Schedule
, Female
, Follow-Up Studies
, Humans
, Immunoglobulin M/blood
, Male
, Middle Aged
, Neoadjuvant Therapy
, Receptors, IgG/genetics
, Rituximab
, Thalidomide/adverse effects
, Treatment Outcome
, Waldenstrom Macroglobulinemia/blood
, Waldenstrom Macroglobulinemia/genetics