Abstract 3427: Split-dose R-CHOP: A novel approach to administer cytotoxic chemotherapy to geriatric patients with DLBCL
Authors: Shah Nirav , Mitra Nandita , Brikman Joshua , Nasta Sunita , Landsburg Daniel , Mato Anthony , Vogl Dan , Frey Noelle , Schuster Stephen , Svoboda Jakub 
Published: August 2015

Abstract
Introduction
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. R-CHOP 21 (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone given in 21 day cycles) is the standard chemotherapy for DLBCL. Due to age-related comorbidities, this regimen may be too toxic for the geriatric population. At our institution we have developed a modified regimen for the frail elderly termed split-dose R-CHOP (SD R-CHOP). Patients (pts) receive CHOP at a 50% dose reduction on day 1 and day 15 of each 28 day cycle. Rituximab is given at full dose on day 1 of each cycle. The total amount of chemotherapy delivered during each 28 day cycle of SD R-CHOP is equivalent to the total doses in R-CHOP 21. All pts are supported with G-CSF after each half cycle.
Methods
We performed a cohort study of DLBCL pts treated with SD R-CHOP since 2007 at our institution. International prognostic index (IPI) and Charlson Comorbidity Index (CCI) were calculated retrospectively for all pts. Descriptive and survival analyses using the Kaplan-Meier methodology and univariate Cox-Proportional hazard models were performed. The primary endpoints, overall survival (OS) and progression free survival (PFS) were estimated from the date of first SD R-CHOP to death, progression, or end of follow-up.
Results
We identified 20 pts with DLBCL treated with SD R-CHOP. The median age was 82 (range 60 to 90 years) and 70% were female. 14 pts had an elevated LDH and 13 pts had stage III/IV disease. Pts had a mean IPI of 3 and a mean CCI score of 2. Of the 20 pts, 9 completed prescribed treatment and achieved a complete response on post-treatment imaging. Of the remaining 11 pts, 2 are in the midst of treatment, 3 died during treatment, and 6 required further modification of treatment due to infectious complications or organ toxicity. The cause of death in those three pts included pulmonary emboli (N = 1), progressive lymphoma (N = 1), and myocardial infarction (N = 1). 13/20 pts required hospitalization during chemotherapy.
The median OS for all pts treated with SD R-CHOP was 47 months and the median PFS was 43 months. For the 9 pts who completed treatment, the median OS was not reached and the PFS was 50 months. Univariate Cox analysis revealed that age, sex, elevated LDH, CCI, IPI, and stage of disease did not impact OS. However, pts who did not complete their prescribed therapy had a hazard ratio (HR) for OS of 5.7 (95% CI 1.2 to 27.3, p = 0.03) and those who were hospitalized had a HR for OS of 5.9 (95% CI 0.74 to 46.6, p = 0.09).
Conclusions
The treatment of aggressive DLBCL in older patients remains a challenge in geriatric oncology. Our SD R-CHOP approach allowed administration of the same total chemotherapy dose as R-CHOP 21 in a geriatric population felt not to be fit for the standard regimen. With this dose modification patients who were able to complete therapy achieved durable responses. We plan to validate these results in a larger prospective trial.
Citation Format: Nirav Shah, Nandita Mitra, Joshua Brikman, Sunita Nasta, Daniel Landsburg, Anthony Mato, Dan Vogl, Noelle Frey, Stephen Schuster, Jakub Svoboda. Split-dose R-CHOP: A novel approach to administer cytotoxic chemotherapy to geriatric patients with DLBCL. [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 3427. doi:10.1158/1538-7445.AM2015-3427