Randomized, double-blind, phase 2, study evaluating same-day vs next-day administration of pegfilgrastim with R-CHOP in non-Hodgkin’s lymphoma patients

Abstract

7570 Background: R-CHOP is associated with a high risk of febrile neutropenia (FN). Pegfilgrastim is indicated to lower infection incidence, manifested by FN, when administered once-per-cycle 24 hrs after chemotherapy (CT). However, eliminating an office visit the day after CT is desirable. Methods: Pts ≥ 18 years with previously untreated non-Hodgkin’s lymphoma (NHL) who received R-CHOP (rituximab 375 mg/m2, C 750 mg/m2, H 50 mg/m2, O 1.4 mg/m2, prednisone 100 mg; for 6 cycles Q21D) were randomized 1:1 to pegfilgrastim 6mg within 4 hours or ∼24hrs after CT. The primary endpoint was the duration of severe (grade 4) neutropenia (DSN) in cycle 1. Same-day administration was considered noninferior to next-day if the upper limit of the 2-sided 95% CI for the difference in mean cycle 1 DSN (same day - next day) was <2 days. Results: 77 pts (8 mantle-cell, 69 diffuse large B-cell) were enrolled of 90 planned (due to slow accrual). 75 pts (36 same-day, 39 next-day) received CT and pegfilgrastim. Most pts had stage 3/4 disease (69% same-day, 74% next-day), no bone marrow involvement (75% same-day, 69% next-day) and ECOG status 0 or 1 (94% same-day, 97% next-day). Difference in mean cycle 1 DSN was 0.9 days (95% CI: 0.3–1.4) longer in the same-day than the next-day group (mean [SD]: 2.1 [1.22] vs 1.2 [1.20] days; grade 4 neutropenia incidence: 86% vs 64%). In cycle 1, more pts had a DSN ≥ 3 days in the same-day (36%) than the next-day group (15%). In cycle 4, mean DSN was longer in the same-day than the next-day group (mean [SD] 1.4 [1.40] vs 0.7 [0.94] days; grade 4 neutropenia incidence: 57% vs 42%). Pts in the 2 groups had similar occurrence of FN (17% vs 15%) and serious adverse events (33% vs 36%) across the study. Full dose on schedule, and the incidence of IV anti-infective use or hospitalization due to FN were also similar between groups. Conclusions: In cycles 1 and 4, the mean DSN was nearly 1 day longer for pts in the same-day group compared with the next-day group. Although the protocol-specified 2-day non-inferiority margin for DSN was met, for pts with NHL receiving R-CHOP, we recommend administering pegfilgrastim 24 hours after CT per labeling guidelines. [Table: see text]