A Comparison of Acute and Delayed Infection Rates among Patients with Indolent Lymphoid Malignancies Receiving Fludarabine(F) and Cyclophosphamide(C) with or without Rituximab(R).

The monoclonal anti-CD20 antibody R improves response rates and survival when added to FC in patients with CLL (Keating Proc ASCO 2004, abstr #6565), but the associated B-cell depletion may increase the infectious risk associated with FC therapy. We therefore compared infectious episodes both during and in the 12 months following therapy in two cohorts of patients treated with FC (F 25mg/m²x3, C 250mg/m²x3 q28 days; n=63) alone or with R (FCR; FC+R 375mg/m² day 1; n = 91) for indolent lymphoid malignancies. Patients received FC from 10/96 to 12/00 and FCR from 12/00 to 8/03. Both cohorts had similar baseline characteristics including history of infections, neutrophil counts, and Ig levels and were mainly elderly (median age 60 years, range 30–89) with heavily pretreated disease (median number of previous therapies 2, range 1–10) and both received a median of 4 cycles of therapy without routine antibiotic prophylaxis or growth-factors; CLL or follicular lymphomas constituted over two-thirds of group. In comparison to FC, infectious episodes were not significantly increased for FCR either during therapy (FC 15%/cycle vs FCR 20%/cycle, p=0.17) or in the first 12 months of remission (1 infection per 13 patient-months [PM] for both cohorts). There was a trend to increased late neutropenia in the FCR cohort (14% vs 31% at 3 months; P = 0.15). Grade 3+ infections were similar both during therapy (FC 8%/cycle vs FCR 9%/cycle) and in the first 12 months of remission (FC 1 per 84 PM vs FCR 1 per 35PM, p=0.16), as were rates of herpes virus infections (FC vs FCR: during therapy 1% vs 2%/cycle; during follow-up 1 per 48 vs 1 per 94 PM). We conclude that the addition of R to FC does not result in increased early or late infectious risk above that of FC alone.