CODOX-M/IVAC-R <i>versus</i> DA-EPOCH-R in double hit/triple hit lymphoma patients aged 60 years or under

Intensified chemoimmunotherapy regimens are often used in young patients with double-hit and triple-hit lymphoma (DHL/ THL) despite no survival benefit compared to R-CHOP. Favorable retrospective reports on the application of CODOX-M/IVAC-R are subject to selection bias as only young fit patients can tolerate this treatment. We conducted a retrospective analysis to investigate outcome differences between CODOX-M/IVAC-R and DA-EPOCH-R in DHL/THL patients aged 60 years or younger. One hundred and thirteen patients were identified; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). Eighty percent (39/49) achieved complete (CR) after completing CODOX-M/IVAC-R compared to 58% (37/64) with DA-EPOCH-R. The median follow-up was 5.3 years and 3.3 years for the CODOX-M/IVAC-R and DA-EPOCH-R group respectively. CODOX-M/IVAC-R demonstrated superior event-free survival (EFS) on univariate (hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.31-0.97) and multivariable analysis adjusted for age, BCL translocation (BCL2 vs. BCL6 vs. both), International Prognostic Index score and receipt of autologous stem cell transplant (adjusted HR [aHR]=0.52, 95% CI: 0.29-0.93); however there was no significant influence on OS (aHR=0.92, 95% CI: 0.46-1.84). The 1, 2 and 5 years EFS in the CODOX-M/IVAC-R group was 68.3%, 64.1% and 61.5%, respectively compared to 52.4%, 48.9% and 39.5%, respectively in the DA-EPOCH-R group. Primary refractory disease or relapse (R/R) occurred in 33% (16/49) of CODOX-M/IVAC-R and 54% (35/64) of DA-EPOCH-R recipients, and produced median OS of 10.3 months and 33.7 months, respectively, indicating poor outcomes in the CODOX-M/IVAC-R subgroup with R/R disease. More patients were able to receive subsequent salvage therapies in the DA-EPOCH-R group. No patients died of regimen toxicity and the rates of central nervous system relapse and therapy related hematologic neoplasms were similar in both groups.