Impact of pegfilgrastim approval on relative dose intensity and outcomes of R-CHOP for diffuse large B-cell lymphoma.

Abstract

Maintaining relative dose intensity (RDI) of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improves the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). Pegfilgrastim was approved in Japan in November 2014 to prevent febrile neutropenia (FN) and maintain RDI.In this retrospective study, we reviewed 334 patients with DLBCL who received 6 or more courses of R-CHOP and analyzed the differences in the RDI, overall survival (OS), and progression-free survival between patients whose treatment started after November 2014 (postapproval group) and those whose treatment started before October 2014 (pre-approval group).The incidence of FN was lower (20% vs 38.3%, P < .001) and the RDI of R-CHOP was higher (86.8% vs 67.8%, P < .001) in the postapproval group. Pegfilgrastim was administered to many of these patients (76.8%) and was thought to have contributed to the high RDI maintenance in the postapproval group. Interrupted time-series analysis showed a significant rise of the RDI at the timing of pegfilgrastim approval in patients aged <70 years (estimated change: 18.1%, P < .001). The 5-year OS (85.7% vs 69.9%, P = .009) and progression-free survival (81.4% vs 64.4%, P = .011) were superior in the postapproval group. However, the differences were not significant in matched-pair analysis matching National Comprehensive Cancer Network-International Prognostic Index scores. Improved survival outcomes in this group were observed only among patients with Ann Arbor stage 3/4 (5-year OS: 83.7% vs 61.3%, P = .019) and high-risk on the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 80.7% vs 32.4%, P = .014). Multivariate analysis showed that a high RDI and low lactate dehydrogenase were associated with superior OS (RDI ≥ 85%, hazard ratio: 0.48, P = .016; lactate dehydrogenase > institutional upper limit of normal, hazard ratio: 2.38, P = .005).The RDI of R-CHOP was able to be maintained at higher levels, the incidence of FN was lower, and significantly better clinical outcomes were achieved in clinically high-risk groups after pegfilgrastim approval. Maintaining a high RDI in R-CHOP by administering pegfilgrastim to those who are likely to have low RDI without it is important for achieving favorable outcomes in patients with DLBCL.