Phase II Pilot Study of Rituximab + CHOP in Patients with Newly Diagnosed Waldenström’s Macroglobulinemia, an Eastren Cooperative Oncology Group Trial (Study E1A02).

Waldenstrom’s Macroglobulinemia (WM) is a low-grade lymphoplasmacytic disorder associated with an IgM monoclonal protein that may present with anemia, lymphadenopathy, and hepatosplenomegaly. Since combination chemotherapy and Rituximab are both active in this disease, it is possible the response rate can be enhanced by using a combined modality of Rituximab and CHOP. This approach has been used in indolent lymphoma with remarkable results and limited toxicity. Objective: To determine the response rate in previously untreated patients with Waldenstrom’s Macroglobulinemia receiving rituximab and CHOP. Methods: This was a phase II study of standard R-CHOP in symptomatic WM patients. The study was activated on June 15, 2004 and closed on April 26, 2007 due to poor accrual. The median age of the sixteen patients enrolled was 60 (44–79 years), β 2 M 3 ug/ml (2.1–7.6), median hemoglobulin was 9 g/dl (7.7–10.9), Viscosity 3.4(1.6–10), and IgM 6389 (3229–13300 mg/dl). The most common symptoms were Fatigue (13/16), visual disturbance (7/16) and parasthesias or painful/numb feet (6/16). Only one patient had bulky adenopathy (6.3%). Results: Of 16 patients treated, 5 patients have no response data available (it will be presented at the meeting). Objective response was 91% (90% CI: 63.5% ∼ 99.5%) and 1 patient had a minor response with an overall response rate of 100%. Median time to response was 1.6 months from registration and median time to maximum response was 2.1 months. Median duration of response has not been reached. The median follow up time of the 16 patients was 18.3 months with a range of 3.6–24.8 months. Among the 16 treated patients, there were 8 (50%, 90% exact binomial CI: 27.9%∼72.1%) grade 4 neutropenia. 8 patients experienced grade 3 lymphopenia (50%, 90% exact binomial CI: 27.9%∼72.1%). Only 2 grade 3 febrile neutropenia were noted. As of August 4, 2007, none of the 16 patients has died. R-CHOP is a promising regimen in the treatment of patients with Waldenstrom’s Macroglobulinemia. To succeed in completing clinical trials in this rare disease better international collaboration and involvement in advocacy groups are required.