Comparison Of Treatment Outcomes with EPOCH-Rituximab Versus CHOP-Rituximab in Patients with De-novo Intermediate and High Risk International Prognostic Index(IPI)Diffuse Large B Cell Lymphoma(DLBCL): A Single Center Retrospective Analysis
Authors: Jain Hasmukh , Sengar Manju , Menon Hari , Dangi Uma , Bagal Bhausaheb , Khattry Navin , Epari Sridhar , Shet Tanuja , Gujral Sumeet , Rangarajan Venkatesh , Laskar Siddhartha 
Published: October 2019

Abstract
Poor prognosis DLBCL, including intermediate and high risk disease according to IPI accounts for approximately 20% of new cases of DLBCL. The addition of rituximab to conventional chemotherapy (CHOP) has improved the outcomes in this subset, with a 2-year overall survival (OS) of about 50%. However, 40-50% of these patients still have either primary refractory disease or relapse after an initial response. Rituximab-EPOCH (R-EPOCH), an infusional regimen has a dynamic dose adjustment strategy based on the hematopoietic nadir in previous cycle to achieve an optimal drug concentration. Phase II studies with R-EPOCH in untreated DLBCL with intermediate and high risk IPI have reported improved outcomes, with an estimated 2-year OS of 75% which appears superior to that of R-CHOP. Hence we analysed the outcomes of patients with de-novo, poor prognosis (intermediate and high risk IPI) DLBCL who received R-EPOCH and compared it to the historical cohort of patients who were treated with R CHOP at our centre.

Methods
Treatment-naïve patients of DLBCL with intermediate or high risk IPI, registered at our centre between November 2011 to June 2013, who received R-EPOCH regimen, were included for the analysis. Case records were reviewed for – demography, histology, stage, bulk of disease, extranodal sites, performance status, IPI, LDH, albumin, details of chemotherapy, grade ¾ toxicities (CTCAE version 4) and need for hospitalization. Responses were evaluated at mid and end of chemotherapy. Overall and progression free survival were calculated. Similar analysis was done for poor prognosis DLBCL patients treated with R-CHOP between Jan 2007 to December 2010.

Results
Baseline characteristics and treatment outcomes of 32 patients (males-24, females-8) treated with R-EPOCH were compared to 42 patients (males-28, females-14) who received R- CHOP. Median age in R- EPOCH group was 47 years (range-20-75 years) versus 55 years (23-72 years )in R- CHOP. Performance status≥ 2 was seen in 47% in R- EPOCH as compared to 28% in R-CHOP group. Significant proportion of patients in R-EPOCH had bulky disease(81% versus 16%) and stage III/IV disease (90% versus 81%) as compared to R-CHOP. Patients with IPI of two represented 8(25%), IPI of three, 11(34%), and IPI of four and five, 10(32%) on R- EPOCH compared to 21(50%), 19(45%) and 2(5%) on R-CHOP, respectively. Serum albumin<3.5 gm/dL was seen in 10(32%) on R-EPOCH and 14(33%) on R-CHOP. LDH was elevated in all but two patients on R-EPOCH compared to 37(88%) patients on R-CHOP. Complete response was seen in 60%, and disease progression in 18% patients on R-EPOCH, compared to 59%, and 20% on R-CHOP respectively. There were 5 deaths on R-EPOCH, 3 due to toxicity and 2 due to disease progression, and in comparison there were 4 deaths on R-CHOP, all of them due to disease progression. With a median follow up of 6 months, the estimated OS at 1 year is 74% and progression free survival (PFS) is 62% for patients on R- EPOCH. For patients on R- CHOP, with a median follow up of 31 months, 1 year OS is 68% and PFS is 64%.

Conclusion
Our retrospective analysis indicates that treatment with R-EPOCH regimen resulted in similar results as with R-CHOP regimen. However patients treated with R-EPOCH had more adverse features in terms of disease bulk, poor performance status and high IPI score. A prospective randomized comparison is warranted between these two regimens.

Disclosures:
No relevant conflicts of interest to declare.