Ryan, T.

8004 Background: To determine optimal induction and the role of maintenance, the E1496 study randomized patients (pts) to induction CVP (cyclophosphamide, vincristine, prednisone) versus CF (cyclophosphamide 1 G/m2 d1, fludarabine 20 mg/m2 d1–5 every 28 d) for 2 cycles beyond best response (maximum 8). Responding and stable pts were secondarily randomized to MR (375 mg/m2 weekly × 4 every 6 months for 2 years [yr]) or observation (OBS). Methods: Due to early deaths the CF arm was closed to accrual with 115 pts randomized to CF and 119 pts to CVP (thereafter all pts were assigned to CVP prior to maintenance randomization). The results presented here compare the outcome of CF patients with the subset of E1496 pts randomized to CVP (CVPR). Results: Median follow-up on pts randomized to induction is 6.5 yr. Toxic deaths occurred in 8 (7%) CF pts during induction and 4 additional deaths (1 OBS, 3 MR) occurred among the 69 (6%) CF pts randomized to MR or OBS. Causes of death were infection (9), liver failure (2), CNS gliosis (1). CF pts received a median of 5 cycles compared to 7 cycles for CVPR. The CR rate was 51% vs 22% (p=0.00001) and the PR rate was 35% vs 55% for CF vs. CVPR, respectively. Four-yr PFS for CF vs. CVPR was 49% vs 45% (p=0.19) and OS was 66% vs. 81% (p=0.12), respectively. Of 45 CF deaths, 23 (51%) occurred without lymphoma progression compared to 5 (13%) of 38 CVPR deaths (p=0.0004). More than 90% of CF patients randomized to maintenance achieved protocol-defined minimal residual disease compared with 64% CVPR pts. Maintenance therapy had no impact on 2 yr PFS for the 67 evaluable randomized CF pts, which was 74% for MR vs. 73% for OBS (p=0.19). In contrast, 2 yr PFS was 73% for MR and 42% for OBS in randomized CVPR pts (p=0.004). Survival at 2 yr for MR vs OBS was: CF 79% vs 91% (p=0.19) compared with CVP 98% vs 93% (p=0.21). Conclusions: Induction with CF results in higher CR and miminal residual disease rates than CVP. However, gains in remission quality with CF (in the dose and schedule used here) were offset by early and late deaths in the absence of progressive lymphoma. In E1496, the benefit of MR was influenced by the induction chemotherapy. [Table: see text]