Abstract 4525: The impact of chemoimmunotherapy dose intensity in diffuse large b-cell lymphoma
Authors: Chu Michael P. , Ghosh Sunita , Belch Andrew , Chua Neil S. , Fontaine Amelie , Sangha Randeep , Turner Robert , Venner Christopher , Baracos Vickie , Sawyer Michael B. 
Published: August 2015

Abstract
Introduction
Chemotherapy dose intensity (DI) impacts outcomes across tumor subtypes. In diffuse large B-cell lymphoma (DLBCL), DI played a large role prior to rituximab, but is still a subject of investigation. Research into intensifying treatment for poorer prognostic lymphoma subtypes has yielded dose-adjusted EPOCH-R where etoposide is added to standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Though, R-CHOP given every 14 vs. 21 days has not been found to improve survival, this study examines if delays in treatment or reductions in R-CHOP21 DI impact patient outcomes.
Methods
In this single institution review, DLBCL patients (pts) treated with first-line R-CHOP between 2004 and 2010 were included. After factoring in covariates such as revised International Prognostic Index (R-IPI) and gender, pts were compared by DI (ratio of actual total dose received vs. prescribed dose) of cyclophosphamide, doxorubicin, and treatment duration as a whole for their impact on progression-free (PFS) and overall survival (OS).
Results
Of 232 pts identified, 224 were included in final review. Median age and ECOG performance status was 62 years and 1, respectively. Majority had stage IV disease (46%). 124 patients were male with pts evenly distributed between R-IPI 0-1 (low, 28%), 2 (low-intermediate, 21%), 3 (high-intermediate, 26%), and 4-5 (high, 25%). A median DI of both cyclophosphamide and doxorubicin was 97%. 118 pts had &gt;/ = 1 week delay during treatment duration. Cutpoint analysis found that DI was more important at 85% for both cyclophosphamide and doxorubicin. Median PFS for patients who received / = 85% cyclophosphamide DI was 27.2 vs. 55.0 months (hazard ratio [HR] 2.48, p = 0.03). Similarly, median OS was 41.8 months vs. not reached (HR 2.79 p = 0.02), respectively. PFS and OS for doxorubicin was similar at 27.6 vs. 53.7 months (HR 2.25, p = 0.04) and 40.9 months vs. not reached (HR 2.54, p = 0.02), respectively. Actual treatment durations that differed &lt;15% of the planned durations were protective for PFS (HR 0.44, p = 0.008), but less so for OS (HR 0.63, p = 0.18). Taking R-IPI scores and gender in multivariate Cox proportional hazards modeling found the impact of cyclophosphamide and doxorubicin DI on PFS and OS maintained significance but not treatment duration. Though multiple reasons for reduced DI exist, growth factor support use trended towards higher DI pts (32 vs. 19%, p = 0.10).
Conclusions
While intensifying R-CHOP by shortening cycles to every 14 days has not been beneficial, this study suggests that delays and dose reductions in R-CHOP21 substantially impact outcomes. In doing so, it highlights that maintaining pts on schedule is important and that more accurate methods of determining appropriate chemotherapeutic doses may affect both survival and toxicity. Although it is our standard to only use growth factor support with delays it may be beneficial to starting all patients up front on growth factor support.
Citation Format: Michael P. Chu, Sunita Ghosh, Andrew Belch, Neil S. Chua, Amelie Fontaine, Randeep Sangha, Robert Turner, Christopher Venner, Vickie Baracos, Michael B. Sawyer. The impact of chemoimmunotherapy dose intensity in diffuse large b-cell lymphoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4525. doi:10.1158/1538-7445.AM2015-4525