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

• Published in: Haematologica (Roma) Vol. 110; no. 2; pp. 448 - 456
• Main Authors: Atallah-Yunes, Suheil Albert, Rees, Matthew J., Witzig, Thomas E., Habermann, Thomas M., Munoz, Javier, Iqbal, Madiha, McPhail, Ellen D., Nowakowski, Grzegorz S.
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.02.2025; Ferrata Storti Foundation
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Cytarabine; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Etoposide - administration & dosage; Etoposide - therapeutic use; Female; Humans; Ifosfamide; Lymphoma - drug therapy; Lymphoma - genetics; Lymphoma - mortality; Male; Middle Aged; Non-Hodgkin Lymphoma; Prednisone - administration & dosage; Prednisone - therapeutic use; Retrospective Studies; Rituximab - administration & dosage; Rituximab - therapeutic use; Treatment Outcome; Vincristine - administration & dosage; Vincristine - adverse effects; Vincristine - therapeutic use; Young Adult
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2024.286168

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. 113 patients were identified; CODOX-M/IVAC-R (N=49) and DA-EPOCH-R (N=64). 80% (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 EFS on univariate (HR=0.54, 95%CI=0.31-0.97) and multivariable analysis adjusted for age, BCL translocation (BCL2 vs BCL6 vs both), IPI score and receipt of ASCT (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 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 CNS relapse and therapy related hematologic neoplasms were similar in both groups.