UGT1A1 6 polymorphism predicts outcome in elderly patients with relapsed or refractory diffuse large B-cell lymphoma treated with carboplatin, dexamethasone, etoposide and irinotecan

• Published in: Annals of hematology 2015, Vol.94 (1), p.65-69
• Main Authors: Yamasaki, Satoshi, Tanimoto, Kazuki, Kohno, Kentarou, Kadowaki, Masanori, Takase, Ken, Kondo, Seiji, Kubota, Akira, Takeshita, Morishige, Okamura, Seiichi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Carboplatin - administration & dosage; Dexamethasone - administration & dosage; Etoposide - administration & dosage; Female; Follow-Up Studies; Glucuronosyltransferase - genetics; Hematology; Humans; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Article; Polymorphism, Genetic - genetics; Prospective Studies; Recurrence; Treatment Outcome
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-014-2170-5

The uridine diphosphate glucuronosyltransferase (UGT) gene 1A1*6 polymorphism, which affects irinotecan metabolism, has been associated with improved survival in lymphoma patients treated with of carboplatin, dexamethasone, etoposide and irinotecan (CDE-11). This study assessed the efficacy of CDE-11 relative to the UGT1A1 *6 polymorphism in 27 elderly patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for high-dose chemotherapy plus autologous stem cell transplantation. The 2-year survival rate after initial CDE-11 treatment was significantly higher in patients with than without UGT1A1 *6 (57% vs. 5%). The most common grade 4 adverse event in patients with the UGT1A1 *6 genotypes was neutropenia (88.9%), but there were no gastrointestinal adverse events or treatment-related deaths. Disease progression was the most frequent cause of death. CDE-11 was well tolerated and provided clinical benefit to elderly patients with relapsed or refractory diffuse large B-cell lymphoma. The response to CDE-11 likely correlated with UGT1A1 *6 polymorphisms, but further prospective studies are warranted to optimize irinotecan-based chemotherapies relative to UGT1A1 polymorphism.