Are Fludarabine Based Regimens Still Adequate for Relapsed/Refractory Follicular Lymphoma? An 18-Year Single-Center Experience

There are no standard treatment recommendations in relapsed/refractory Follicular Lymphoma (R/R FL). Fludarabine, an effective but toxic agent, has been commonly used, but trials focusing on the risk-benefit balance in this setting are lacking and novel agents are available. We conducted a single-center cohort study to evaluate the toxicity profile and supportive care needs of fludarabine-based regimens (FBR) administered in the first or second relapse. We retrospectively evaluated 116 R/R FL patients. Of these, 78 (67%) received FBR and 38 (33%), who were analyzed as an internal reference, received alkylating-based regimens (non-FBR). Similar disease control was obtained with both treatments. Treatment-related toxicities were high in FBR (74%) and non-FBR patients (68%). Growth factor use, transfusion requirements, short-term admissions to emergency room and prolonged hospitalization for toxicity were similar in FBR and non-FBR patients, but the latter were older and had different co-morbidities. FBR patients over 60 years had higher incidences of grade ?2 infections (46% vs. 18%; p=0.008). These regimens lead to prolonged hematological recovery, compromising subsequent treatments. With a median follow up of approximately 5 years, secondary malignancies were reported in 14% of patients. High FBR toxicity and the availability of effective novel agents raise concerns about its adequacy in R/R FL setting. Therapeutic choices require a careful balance between efficacy, toxicity, cost and feasibility of subsequent therapies.