Similar Incidence Of Febrile Neutropenia With Same-Day Versus Subsequent Day G-CSF Administration In Non-Hodgkin Lymphoma Patients Receiving R-CHOP Chemotherapy

The chemotherapy regimen of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) every 21 days remains a standard first line treatment for many subtypes of B-cell non-Hodgkin lymphoma (NHL). R-CHOP chemotherapy carries a significant risk of febrile neutropenia (FN). FN is a potentially life threatening complication which typically requires hospital admission and empiric administration of broad spectrum antibiotics. FN can also cause delays and dose reductions with treatment, which are associated with poorer outcomes. Granulocyte colony stimulating factors (G-CSF) are indicated for primary prophylaxis with high risk patients to ameliorate this serious complication of treatment. Prescribing guidelines recommend that G-CSF’s not be given until 24 hours after receiving chemotherapy. However, due to logistical issues of outpatient insurance coverage, travel, and patient convenience, it is not always practical to delay G-CSF administration until the day after chemotherapy. Therefore, some patients at our institution received G-CSF on the same day as chemotherapy.

We identified 113 lymphoma patients treated with R-CHOP who also received G-CSF primary prophylaxis at our institution from 6/21/04-1/12/12. G-CSF primary prophylaxis with daily filgrastim or a single dose of pegfilgrastim was administered within the first six days of starting R-CHOP, categorized as either same day (D1) or later (D2+). We retrospectively analyzed FN incidence and associated outcomes in patients receiving growth factor as primary prophylaxis administered the same day compared with >24 hours after chemotherapy. FN was estimated using the cumulative incidence method and compared between groups with the Pepe-Mori test. Cox analysis was used to identify prognostic factors for survival and relapse-free survival.

In our study, 113 patients received R-CHOP and G-CSF as primary prophylaxis (31 D1, 82 D2+). FN occurred in 8 out of 31 D1 patients (25.8%), and in 21 out of 82 patients in the D2+ group (25.6%). FN incidence did not differ between the two groups (P=0.91). No significant differences in relapse-free or overall survival were observed. Risk factors associated with mortality in multivariable analysis included development of FN (hazard ratio 4.33, 95% CI 1.88-10.0, P<0.001) and receiving R-CHOP while hospitalized as an inpatient (hazard ratio 7.16, 95% CI 3.08-16.6, P<0.001).

Among patients receiving G-CSF as primary prophylaxis with R-CHOP, we observed no difference in FN between G-CSF administered the same day and D2+. Not surprisingly, the development of FN and receiving R-CHOP while hospitalized, were both found to be significant risk factors associated with mortality. Previous prospective studies showed more severe and prolonged level of neutropenia, with higher rates of FN with same day versus next day administration in a small cohort of R-CHOP treated NHL patients (Burris et al, 2010). In our retrospective study, we were not able to evaluate neutrophil levels at multiple time points throughout each cycle, and longer follow-up is necessary to evaluate other long-term endpoints of potential interest, such as the incidence of secondary myeloid malignancies after same-day versus next-day G-CSF treatment. For patients who require G-CSF support, next day administration remains the recommended schedule. However, same day administration may be a reasonable alternative if access to care and patient compliance are concerns.

Hill:Celgene: Honoraria, Research Funding.