2-Chlorodeoxyadenosine (2-CdA) and Cyclophosphamide (Cy) Alone or in Combination with Rituximab (Rit) for Previously Untreated Waldenstrom’s Macroglobulinemia (WM).

Between 3/96-11/03 we treated 62 consecutive, newly diagnosed pts with symptomatic WM with either 2-CdA 1.5 mg/m² sc tid x 7d + Cy 40 mg/m² po bid x 7d (35 pts, 3/96-2/99) or with identical doses of 2-CdA and cyclophosphamide + Rit 375 mg/m² IV q wk x 4 wk (27 pts, 11/98-11/03). For both regimens a second and final course was repeated after 6 weeks. Partial response (PR), defined by at least 50% reduction of monoclonal IgM, adenopathy, and organomegaly, was noted in 83% (29 pts) of pts treated with 2-CdA-Cy and 81% (22 pts) with 2-CdA-Cy-Rit; complete disappearance of clonal evidence of disease (CR) by negative serum and urine immunofixation, bone marrow, and CT scan was noted in 6% (2 pts) treated with 2-CdA-Cy and 11% (3 pts) with 2-CdA-Cy-Rit. Overall response rate was 89% and 93% for 2-CdA-Cy and 2-CdA-Cy-Rit, respectively. Responding patients were followed without further treatment until relapse, defined by a 25% increase in M-protein from nadir, or recurrence of adenopathy or organomegaly. Median time to remission was similar at 2.5 mos for 2-CdA-Cy and 2.4 months for 2-CdA-Cy-Rit (p.42), but time to treatment failure (TTF) appeared longer for 2-Cda-Cy-Rit (med. 64.2 mos) than for 2-CdA-Cy (med. 31.4 mos) (p.20). Since many pts have not required retreatment for symptomatic disease at the time of relapse, we also evaluated time to retreatment (TTRT) as a separate endpoint. The median time to retreatment (TTRT) has not been reached with 2-CdA-Cy-Rit, in comparison with a median TTRT of 51.2 mos with 2-CdA-Cy (p<.01), illustrating the prolonged period of stability after limited treatment with either 2-CdA combination and the superiority of added rituximab. Median overall survival has not been reached with either regimen since only 27% of all pts have died. Both treatment regimens were associated with minimal toxicity, high response rate, long duration of unmaintained remission, even longer time to the need for retreatment, and long survival. Thus treatment with a limited 2-CdA regimen represents the therapy of choice, in our opinion, for previously untreated, symptomatic WM.