Evaluation of Relative Dose Intensity (RDI) by Age in Patients (pts) with Non-Hodgkin Lymphoma (NHL) Receiving Pegfilgrastim and CHOP Based Chemotherapy

The standard of care for aggressive NHL is treatment (tx) with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with rituximab (R). Improved outcomes are associated with retention of dose and schedule. Pegfilgrastim prophylaxis reduces the severity and duration of neutropenia, contributing to fewer dose delays and reductions and higher RDI. A retrospective analysis of pegfilgrastim NHL clinical trials showed that pegfilgrastim primary prophylaxis maintained RDI for CHOP/CHOP-R; a greater number of younger than older pts had > 85% RDI (Mo et al. Pan Pacific Lymphoma Conference 2011; poster). Here we further examine the association of age with RDI for CHOP/CHOP-R in NHL pts receiving pegfilgrastim.

This retrospective analysis pooled data from 5 pegfilgrastim NHL clinical trials (1 single-arm and 4 randomized controlled studies). Pts received up to 6 cycles of CHOP/CHOP-R every 2 (Q2W) or 3 (Q3W) weeks. Data from the pegfilgrastim primary prophylaxis tx arms were combined. RDI and the incidence of dose delay, reduction, discontinuation, and adverse events (AE) leading to dose alteration/discontinuation were analyzed in the CHOP/CHOP-R regimens combined and stratified by age group (< 65, 65–75, and > 75 years [yr] ) and schedule (Q2W and Q3W). RDI during tx exposure and RDI adjusted by the planned 6 cycles of tx were calculated. Overall RDI of the regimen was calculated as the average of RDI of cyclophosphamide and doxorubicin. Dose delay: > 3 days of delay for any cycle after cycle 1. Dose reduction: ≥ 20% reduction from the planned dose of cyclophosphamide or doxorubicin for any cycle. Dose discontinuation: not completing all planned 6 cycles of tx for reasons other than death/disease progression. RDI was also evaluated with a multiple regression model using tx group, age, stage, sex, race and comorbidity as explanatory variables.

In the Q3W regimen (N = 137), 50% of pts were women, 36% had stage IV disease, and 23% were > 75 yr. In studies with available histology data, most pts had diffuse large B cell lymphoma. The incidence of pts with > 85% RDI during tx exposure: 89%, 86% and 81% for pts < 65, 65–75 and > 75 yr, respectively. The incidence of pts with > 85% adjusted RDI: 74%, 55% and 47%, respectively. The incidence of pts who completed all 6 cycles of tx: 78%, 56% and 47%, respectively. The incidence of dose reduction: 7%, 21% and 13%, respectively. The incidence of dose discontinuation: 19%, 36% and 47%, respectively. The incidence of dose delay was similar among age groups. Multiple regression analysis showed age and cancer stage as potential factors associated with RDI (p = 0.0290 and 0.0145, respectively). The table shows AEs leading to dose alteration/discontinuation. Q2W data will be presented separately.

In this pooled population the incidence of pts with > 85% RDI adjusted by the planned 6 cycles of tx was lower in older pts as fewer older pts completed all 6 cycles of tx. Pts < 65 yr had a lower incidence of AE leading to dose alteration/discontinuation. The AE profile was widely spread across hematological and non-hematological toxicities. Unlike prior reports where myelosuppression frequently caused reduced RDI, myelotoxicity was an infrequent cause of therapy alteration/discontinuation with pegfilgrastim primary prophylaxis (< 7%). Pegfilgrastim use in elderly pts maintained RDI during tx exposure. Further research is needed to address non-hematologic causes of tx interruptions in elderly pts receiving CHOP based chemotherapy.

Balducci:Jennsen: Honoraria; Novartis: Honoraria; Cephalon: Honoraria; Amgen Inc.: Honoraria. Mo:Amgen Inc.: Employment, Equity Ownership. Abella:Amgen Inc.: Employment, Equity Ownership.