Changing Patterns of Chemotherapy Delivery and Supportive Care for Aggressive B-Cell Non-Hodgkin's Lymphoma

For several decades, non-Hodgkin's Lymphoma (NHL) has been treated with a CHOP-based chemotherapy regimen with curative intent. In 2004, a large retrospective analysis of patients with aggressive NHL treated at 567 community practices from 1999 to 2001 indicated that only 52% of patients received chemotherapy at a relative dose intensity (RDI) ≥ 85% (Lyman GH, et al. JCO. 2004;22:4302–11). This study showed that primary prophylactic use of colony-stimulating factors (CSF) starting with the first cycle of chemotherapy was associated with a reduced incidence of febrile neutropenia (FN) and was an independent predictor of RDI ≥ 85%. At that time, only about 12% of patients received CSF in the first cycle. To evaluate changes in oncology practice, we reviewed recent treatment patterns, including RDI for delivered chemotherapy and CSF support, for patients with aggressive B-cell NHL at 36 community-based oncology practices and hospitals, the majority of which participated in the previous study.

Patient charts and electronic medical records from January 2006 to December 2009 were reviewed. Patients were included if they had aggressive B-cell NHL, were ≥ 18 years old, and completed ≥ 1 cycle of chemotherapy with the following standard cytotoxic regimens during the chart abstraction period: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); CHOP-rituximab (CHOP-R); or cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). Exclusion criteria included prior stem-cell transplantation, prior/concurrent radiotherapy, and chemotherapy started outside of the chart abstraction period. The primary endpoint was delivered RDI, based on the proportion of chemotherapy actually delivered compared to published standards, as in the previous study. Other endpoints included chemotherapy dose delays and reductions, grade 3/4 neutropenia, grade 3/4 FN, FN-related hospitalization, CSF use, and antimicrobial use.

Records of 500 patients were reviewed. Mean patient age was 63.7 years (range: 18–90), and 55% of patients were male. The majority (90.8%) received CHOP-R chemotherapy on a 21-day schedule (CHOP-R 21) for a mean of 5.5 cycles (range: 1–8). The mean RDI delivered for CHOP-21 ± R was 87.6%. Delivered chemotherapy intensity in the current study was considerably greater than that observed in the previous study with an increase in delivered RDI ≥ 85% (current vs previously published: 71% vs 52%) and a decrease in dose reductions (20.6% vs 35%). Dose delays appear similar between the studies (26.4% vs 23%). In the current study, 67% of patients had grade 3/4 neutropenia, compared to 62% of patients in the previous study. In addition, the incidence of clinical FN (12% vs 20.9%) and the number of patients hospitalized for FN (9.6% vs 15.9%) has decreased. Use of primary prophylactic CSF has increased (75% vs 12%) with a shift from support with filgrastim to pegfilgrastim. Filgrastim was the predominant CSF in the previous study while, in the current study, 78.6% of patients received pegfilgrastim only, and 9.2% of patients received pegfilgrastim and filgrastim. While antimicrobial use was not reported in the previous study, in the current study, 51% of patients received at least one antimicrobial; 13% received prophylactic antimicrobials, and 45.8% received therapeutic antimicrobials.

Patterns of chemotherapy delivery and supportive care have changed markedly for the management of patients with aggressive B-cell NHL. In the United States, CHOP-R 21 is now the most commonly used regimen, as compared to CHOP-21 in the previous study. Average RDI delivered and prophylactic use of CSF, predominantly pegfilgrastim, have increased, while dose reductions, FN, and FN-related hospitalizations have decreased. However, dose delays and reductions are still relatively common, suggesting opportunities for further improvements in the treatment of patients with aggressive B-cell NHL.

Lyman:Amgen: Research Funding. Crawford:Amgen: Consultancy, Honoraria, Research Funding. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Whittaker:Amgen: Employment. Tomita:Amgen: Employment, Equity Ownership.