Myelosuppression can persist after the completion of frontline therapy with fludarabine, cyclophosphamide, and rituximab (FCR) in patients with chronic lymphocytic leukemia (CLL), mostly among elderly patients with baseline cytopenia. Its frequency decreases over time, with no association noted with disease progression, second myeloid malignancies, or infections (unless persisting up to 9 months). The data shown by Gozzetti et al describe grade 3 to 4 hematological toxicity (rather than grade 2 to 4) during treatment (rather than after) in elderly patients with CLL receiving frontline oral FC with rituximab. The observed complete response (CR) rate was 78% and the rate of grade 3 to 4 cytopenia was 15%. In our initial phase 2 study of FCR among patients with a median age of 58 years, the reported CR rate was 70% and grade 3 to 4 neutropenia (the most common hematological toxicity) complicated 52% of courses. During the CLL8 trial (among patients with a median age of 61 years), the CR rate was 44% and grade 3 to 4 neutropenia was observed in 34% of patients. Either calculated per person or cycle, the toxicity reported by Gozzetti et al is lower. It is not clear how many patients had baseline cytopenia, another factor that is significantly associated with myelosuppression in our analysis, and how many received support with growth factor. It is interesting to note that the addition of granulocyte-macrophage–colony-stimulating factor to FCR among patients with a median age of 55 years produced a significant reduction in the rate of severe infections, albeit comparable rates of CR and grade 3 to 4 neutropenia per cycle and per patient. Together with the fact that the addition of rituximab to FCR did not increase the frequency of infections despite a higher rate of neutropenia, these data raise the question of whether limiting hematological toxicity will translate into an actual clinical benefit.
CONFLICT OF INTEREST DISCLOSURES
The authors made no disclosures.
Paolo Strati, MD
Susan O'Brien, MD
Department of Leukemia
The University of Texas MD Anderson Cancer Center