Outcomes of CHOP versus CHOEP/EPOCH in aggressive adult T-cell leukemia/lymphoma: an international cohort analysis

Aggressive adult T-cell leukemia/lymphoma (ATL) subtypes (i.e., acute and lymphomatous) are rare diseases, and the conventional management with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has historically yielded poor outcomes. The benefit of etoposide-containing regimens (CHOEP/EPOCH) in the first-line setting is inconclusive. We compared the effectiveness of CHOEP/EPOCH versus CHOP in aggressive ATL. We conducted an international, multicenter retrospective cohort study among newly diagnosed patients with ATL during 2000-2023 across five Latin American countries and the United States. Study endpoints included overall response rate (ORR) and overall survival (OS). Propensity score weighting was used to balance the treatment groups, and findings are reported for each ATL subtype. Among 328 patients, 108 had acute ATL and 220 had lymphomatous ATL. In weighted analyses, CHOEP/EPOCH was not statistically associated with a higher ORR compared to CHOP in lymphomatous ATL (66% vs. 58%; Odds ratio [OR]=2.08, 95% confidence interval [CI]=0.76-5.75) or acute ATL (42% vs. 58%; OR=0.68, 95% CI=0.06-7.84). With a median follow-up of 34 months (interquartile range [IQR] 15-73) in lymphomatous ATL, CHOEP/EPOCH was associated with a higher 3-year OS (34% vs. 12%; HR=0.55, 95% CI=0.35-0.87). However, with a median follow-up of 63 months (IQR 16-110) in acute ATL, CHOEP/EPOCH was not associated with improved 3-year OS (8% vs. 11%; HR=0.95, 95% CI=0.51-1.77). In conclusion, CHOEP/EPOCH may be associated with improved survival in lymphomatous ATL, while results in acute ATL were inconclusive. These findings support the need for prospective interventional studies to validate the subtype-specific benefits.