Toxicity in patients (pts) age 65 or older with dose-adjusted REPOCH (DA-REPOCH) for untreated diffuse large B-cell lymphoma (DLBCL).

Abstract

e18508 Background: ORR of 97-99% and 5-yr PFS of 75-79% are reported with front-line DA-REPOCH in pts age 19-85. In these prospective series, 72% of pts escalated ≥ 1 dose level (DL), febrile neutropenia (FN) occurred in 36-51% pts, and 3-4% died of toxicity. Methods: We performed retrospective analysis of pts ≥ 65 treated with DA-REPOCH front-line for DLBCL at Ohio State University from 2002-2011. PFS estimates were calculated by the Kaplan-Meier method. Logistic regression and proportional hazards models were fit to identify variables associated with ORR and PFS, respectively. Results: 69 pts ≥ 65 yrs (range, 65-92) received DA-REPOCH for de novo (n=42) or transformed (prior CLL=16, FL=9, HL=2) DLBCL, including 28 pts ≥ 75. Performance status (PS) was ≥ 2 in 43%, 86% were stage III-IV, 77% had an aaIPI ≥ 2, 19% had bulky disease ≥ 10 cm, 83% had extranodal disease, and median creatinine clearance (CrCl) was 64 ml/min. Median number of cycles was 5 (range 1-7). Max DL was 1, 2, and 3 in 72, 13, and 6% of pts, respectively, and 9% received all cycles below DL 1. Max DL and number of cycles were similar between pts 65-74 and > 75. Dose reductions (DR), delays, FN, and hospitalization occurred in 48, 39, 38, and 42% of pts, respectively. DR were associated with age ≥ 75 (p=0.001) or reduced CrCl (p=0.02) and delays strongly associated with PS ≥ 2 (p=0.001). FN was associated with bulky disease (p=0.03); 31% of pts without bulky disease developed FN compared to 67% with bulk. Nine pts (13%, 3 pts ≥ 75) died of toxicity (7 pts at DL 1 and 2 at DL < 1). ORR was 67% (95% CI 52-75%). Median PFS was 17 mos (95% CI 6-43). Increased LDH (p=0.008 and p<0.001) and number of prior chemotherapies (p=0.04 and p<0.001) were independently predictive for ORR and PFS, respectively. DR and age were not associated with ORR or PFS, controlling for LDH and number of prior regimens. In 42 pts with de novo DLBCL, ORR was 71% (95% CI 54-85%) and median PFS was 36 mos (95% CI 7-94). Conclusions: In this retrospective study, toxicity is increased with DA-REPOCH in pts ≥ 65 with DLBCL, compared to published results in a younger population. Age ≥ 75, impaired CrCl, and poor PS are associated with increased risk of DR and delays, although age and DR do not appear to impact ORR and PFS.