Febrile Neutropenia Risk Assessment and Granulocyte-Colony Stimulating Factor Support in Patients with Diffuse Large B Cell Lymphoma Receiving R-CHOP Regimens.

ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy of chemotherapy. In IMPACT NHL, we evaluated current practice in FN risk assessment and use of G-CSF prophylaxis in patients receiving (R)CHOP. METHODS: IMPACT NHL is a retrospective and prospective observational study conducted in 14 European countries and Australia. Physicians assessed the overall FN risk of NHL patients and their need for G-CSF prophylaxis. This analysis focuses on patients with diffuse large B-cell lymphoma (DLBCL) receiving either 2-weekly R-CHOP-14 or 3-weekly R-CHOP-21. FN risk was assessed according to EORTC guidelines (i.e. the total risk from the chemotherapy regimen plus individual patient risk factors). The primary outcome measure was the proportion of patients assessed as being at ≥20% risk of FN and who were planned to receive primary prophylaxis with a G-CSF (defined as G-CSF initiation within days 1-7 of cycle 1). RESULTS: Data were available for 1829 patients who initiated chemotherapy between 01/2005 and 08/2008; 1136 had DLBCL. The mean age±SD of patients receiving R-CHOP-21 (N=704) was 62.6±13.8 years, 51% were aged ≥65 years and 53% had Stage III-IV disease. For R-CHOP-14 patients (N=409), the mean age was 58.4±14.7 years, 41% were ≥65 years and 59% had Stage III-IV disease. In total, 434 R-CHOP-21 patients were assessed as being at high risk for FN and 47% of them actually received G-CSF primary prophylaxis (with either pegfilgrastim or daily G-CSF) (see Table). Furthermore, almost a fifth of patients assessed as being at <20% FN risk received G-CSF primary prophylaxis. Across all cycles, 29% of R-CHOP-21 patients had an unplanned hospitalization, with neutropenia/FN being the main reason. Subsequently, 67% of patients achieved a relative dose intensity (RDI) of ≥90% of their planned treatment (with respect to cyclophosphamide, doxorubicin, and vincristine). In the R-CHOP-14 group, 16% of patients did not receive G-CSF primary prophylaxis; 32% had an unplanned hospitalization and 59% of patients achieved '90% of their planned RDI.

Half of R-CHOP-21 patients assessed as high risk for FN did not receive G-CSF primary prophylaxis despite physicians' awareness of elevated risk, while primary G-CSF support was not given to almost one fifth of R-CHOP-14 patients, contrary to guideline recommendations. Both R-CHOP-14 and R-CHOP-21 resulted in significant myelotoxicity (with substantial FN even in those evaluated as being at lower risk), and only around two-thirds of patients received optimal chemotherapy RDI. Our data suggest that improvements in neutropenia management are required. More consistent use of G-CSF primary prophylaxis may further reduce FN and assist in optimal chemotherapy delivery.

Sponsored by Amgen

Salar:Amgen: Honoraria. Haioun:Roche: Research Funding; Amgen: Other, Research Funding; Celgene: Other, Research Funding; Mundipharma: Research Funding. Pettengell:Amgen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau. Jaeger:Amgen: Research Funding. Schwenkglenks:Amgen: Honoraria, Research Funding. Bacon:Amgen: Employment, Equity Ownership. Bendall:Amgen: Employment.