CD20-directed antibody-mediated immunotherapy induces responses and facilitates hematologic recovery in patients with Waldenstrom's macroglobulinemia

Waldenstrom's macroglobulinemia (WM, lymphoplasmacytic lymphoma) is a B-cel l lymphoproliferative disorder in which CD20 is expressed on tumor cells fr om most patients. Several small studies have suggested a benefit from the a nti-CD20 monoclonal antibody rituximab (Rituxan, MabThera) in patients with WM. In this retrospective study, we examined the outcome of 30 previously unreported patients with WM who received treatment with single-agent rituxi mab (median age 60; range 32-83 years old). The median number of prior trea tments for these patients was 1 (range 0-6), and 14 patients (47%) received a nucleoside analogue before rituximab therapy. Patients received a median of 4.0 (1-11.3) infusions of rituximab (375 mg/m(2)). Three patients recei ved steroids with their infusions for prophylaxis of rituximab-related infu sion syndrome. Overall, treatment was well tolerated. Median immunoglobulin M (IgM) levels for all patients declined from 2,403 mg/dL (range 720-7639 mg/dL) to 1,525 mg/dL (range 177-5,063 mg/dL) after rituximab therapy (p = 0.001), with 8 of 30 (27%) and 18 of 30 (60%) patients demonstrating >50% a nd >25% decline in IgM, respectively. Median bone marrow lymphoplasmacytic (BM LPC) cell involvement declined from 60% (range 5-90%) to 15% (range 0-8 0%) for 17 patients for whom pre- and post-BM biopsies were performed (p < 0.001). Moreover, 19 of 30 (63%) and 15 of 30 (50%) patients had an increas e in their hematocrit (HCT) and platelet (PLT) counts, respectively. Before rituximab therapy, 7 of 30 (23.3%) patients were either transfusion or ery thropoietin dependent, whereas only 1/30 (3.3%) patients required transfusi ons (no erythropoietin) after rituximab. Overall responses after treatment with rituximab were as follows: 8 (27%) and 10 (33%) of the patients achiev ed a partial (PR) and a minor (MR) response, respectively, and an additiona l 9 (30%) of patients demonstrated stable disease (SD). No patients attaine d a complete response. The median time to treatment failure for responding (PR and MR) patients was 8.0 months (mean 8.4; range 3-20+ months), and 5.0 months (mean 6.1; range 3-12+ months) for patients with SD, These studies therefore demonstrate that rituximab is an active agent in WM. Marked incre ases in HCT and PLT counts were noted for most patients, including patients with WM who had MR or SD. A prospective clinical trial to more completely define the benefit of single-agent rituximab in patients with WM has been i nitiated by many of our centers.