A multi-center analysis of the impact of DA-EPOCH-R dose-adjustment on clinical outcomes of patients with double/triple-hit lymphoma

Abstract

Patients with double- and triple-hit lymphomas (DHL/THL) have inferior outcomes with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and higher-intensity regimens such as dose-adjusted (DA)-EPOCH-R are standard. Dose-intensification of DA-EPOCH-R is guided by hematologic toxicity, without conclusive benefit for DHL/THL patients. To determine if cumulative doses of DA-EPOCH-R or compliance with dose adjustment impacts survival, we retrospectively evaluated detailed clinical data from 109 adult (age ≥18 years) patients with DHL/THL treated with ≥4 cycles of induction DA-EPOCH-R from 2014 to 2019 at six centers. A comprehensive multivariate analysis was performed. Survival outcomes for the entire cohort were comparable to historical estimates for DHL/THL treated with this regimen (median follow-up 27.9 months). Overall survival (OS) and progression-free survival (PFS) were not significantly associated with cumulative chemotherapy dose, dose escalation, or compliance with dose adjustment. Heterogeneous dosing practices were observed. Prospective investigation is warranted to evaluate the practice of dose adjustment of R-EPOCH for patients with DHL/THL.

Keywords:

• Double/triple-hit lymphomas
• high-grade B-cell lymphomas
• chemotherapy
• chemoimmunotherapy
• lymphoma
• DA-EPOCH-R

Acknowledgements

Special thanks to our patients and their respective treatment teams at our collaborating institutions, including the Cleveland Clinic Taussig Cancer Institute, Barnes-Jewish Hospital at Washington University in St. Louis, the University of Colorado Cancer Center, the Abramson Cancer Center at the University of Pennsylvania, the Lineberger Comprehensive Cancer Center at the University of North Carolina, and the Division of Hematology/Oncology at the University of Virginia.

Ethics statement

The study protocol was approved by each collaborating institutional review board.

Author contributions

MJC performed the research, analyzed the data, and authored the paper; WW performed the statistical analyses. BTH designed the study, conducted research, and guided and reviewed the production of the manuscript; SC, MPW, MO, GJ, JK, BH, BH, MH, EN, NSG, AS, VO-N, MR, MS, JR, CP, TV, DL, MK, and BK participated in and/or oversaw data collection and reviewed the manuscript. All authors approved the manuscript and the interpretation of the data.

Disclosure statement

The authors declare no competing commercial interests.

Data availability statement

Data are available upon request by contacting the corresponding author.