The presence of genomic imbalances is associated with poor outcome in patients with burkitt lymphoma treated with dose‐intensive chemotherapy including rituximab

Abstract

The introduction of Rituximab has improved the outcome and survivalrates of Burkitt lymphoma (BL). However, early relapse and refractorinessare current limitations of BL treatment and new biological factors affectingthe outcome of these patients have not been explored. This study aimed toidentify the presence of genomic changes that could predict the response tonew therapies in BL. Forty adolescent and adult BL patients treated withthe Dose-Intensive Chemotherapy Including Rituximab (Burkimab) proto-col (Spanish Programme for the Study and Treatment of HaematologicalMalignancies; PETHEMA) were analysed using array-based comparativegenomic hybridization (CGH). In addition, the presence ofTP53, TCF3(E2A), ID3andGNA13mutations was assessed by next-generationsequencing (NGS). Ninety-seven per cent of the patients harboured geno-mic imbalances. Losses on 11q, 13q, 15q or 17p were associated with apoor response to Burkimab therapy (P=0 038), shorter progression-freesurvival (PFS;P=0 007) and overall survival (OS;P=0 009). The integra-tive analysis of array-CGH and NGS showed that 26 3% (5/19) and 36 8%(7/19) of patients carried alterations in theTP53andTCF3genes, respec-tively.TP53alterations were associated with shorter PFS (P=0 011) whileTCF3alterations were associated with shorter OS (P=0 032). Geneticstudies could be used for risk stratification of BL patients treated with theBurkimab protocol.