Clinical Outcomes and Cost Analysis of Dose-Adjusted R-EPOCH Vs R-CHOP in Treatment of Diffuse Large B- Cell Lymphoma with High Risk Features
Authors: Dholaria Bhagirathbhai , Vishnu Prakash , Moreno-Vanegas Yenni Alejandro , Spaulding Aaron C. , Diehl Nancy N. , Hodge David , Rivera Candido E. , Tun Han 
Published: October 2019

Abstract

Background
Diffuse large B cell lymphoma (DLBCL) with high-risk features carries a poor prognosis despite treatment with immunochemotherapy regimen incorporating rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Hence, dose adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA.R-EPOCH), a higher intensity regimen, is suggested as an upfront treatment of high-risk DLBCL. In our study, we analyzed the outcomes in a prospectively followed cohort of patients with de novo high-risk DLBCL who received DA.R-EPOCH, and compared them to the patients who received R-CHOP. Furthermore, we conducted a cost analysis to determine which of the two treatments produces a larger financial burden.
Method
Patients diagnosed with DLBCL who received chemo-immunotherapy at our center between January 2011 to December 2016 were included in the analysis. High-risk DLBCL was defined by the presence of any of the following features at diagnosis: NCCN- IPI score ≥4, tumor measuring ≥5 cm, MYC ± BCL2 or BCL6 rearrangement by FISH or MYC overexpression (>40% by immunohistochemistry [IHC]), Ki-67 index ≥80% and non-GCB immunophenotype by Hans algorithm. Responses were evaluated at middle and end of chemotherapy. Overall (OS) and progression free survival (PFS) were calculated. For the cost analysis, standardized costs were obtained from Mayo Clinic Florida cost data warehouse based upon patient encounters and treatments. Report cost-to-charge ratios were multiplied by the charges for all hospital billed services, and all resulting costs were adjusted to 2016 dollars with the Gross Domestic Product (GDP) Implicit Price Deflator. Patients who did not receive their complete planned treatment at our facility were excluded from the cost analysis.
Results
Of 80 patients with high-risk DLBCL, 52 (65%) patients were treated with R-CHOP and 28 (35%) with DA.R-EPOCH. The median follow-up was 11.2 months (range: 0.7- 151.3 months). The planned treatment completion rate and complete remission rate at the end of treatment were similar in both groups. There was no significant difference in OS and PFS among the patients treated with DA.R-EPOCH compared to R-CHOP. The hazard ratio (HR) for PFS was 0.79 (95% CI- 0.28-2.29, P=0.67) and OS was 0.86 (95% CI- 0.26-2.78, P=0.80) (Figure 1). In Cox-regression analysis, low baseline albumin, ECOG performance status ≥2, above-normal LDH, high NCCN- IPI and low cumulative chemotherapy doses were associated with poor OS and PFS. Overall incidence of grade ≥ 3 neutropenia, neuropathy, and unplanned hospitalizations were similar between the two treatment groups. Patients treated with DA.R-EPOCH required more red cell transfusions during the treatment (P=0.004). The total mean cost associated with DA.R-EPOCH and R-CHOP regimens was $106,940 ± $39,351 and $58,509 ± 24,588, respectively (P<0.001). The cost associated with hospital services, laboratory testing and evaluation and management were higher in DA.R-EPCOH group compared to R-CHOP group (P<0.001) (Table 2).
Conclusion
Our study showed that there was no significant difference in PFS and OS of patients with DLBCL with high-risk features when treated with R-CHOP compared to DA.R-EPOCH. DA.R-EPOCH was associated with higher red cell transfusion requirement and treatment related expenses. A prospective randomized comparison is warranted between these two regimens specifically for patients with high-risk DLBCL.

Disclosures
No relevant conflicts of interest to declare.