Genetic and Prognostic Analysis in Blastoid and Pleomorphic Mantle Cell Lymphoma: A Multicenter Analysis in China

Abstract

Blastoid and pleomorphic mantle cell lymphoma (B/PMCL), which are characterized by more highly aggressive features and an unfavorable outcome, are still a diagnostic and therapeutic challenge in MCL. In this study, we aimed to integrated analysis of clinical, genomic characteristics and treatment options of patients with blastoid/pleomorphic mantle cell lymphoma in China from multicenter. Second generation sequencing was performed in evaluable biopsy specimens. Seventy-four patients with blastoid (n=43) and pleomorphic (n=31) were included in the analysis. Median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. 3-year progression free survival (PFS) and overall survival (OS) rates were 37.6% and 46.0%, respectively. The most common gene mutations in blastoid/pleomorphic MCL were TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, TRAF2. Progression of disease within 12 months (POD12) can distinguish the worst prognosis in blastoid and pleomorphic variants. Which carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP and CDKN2A mutations) compared with non-POD12 patients. Gene with POD≤12 was enriched in BCR signaling while gene with POD>12 were enriched in TRAF3-dependent IRF activation pathway. First-line high dose cytarabine exposure obtained survival benefits in these population, and BTKi-combined treatment in front-line had somewhat improvement in survival with no significant difference in statistic. In conclusion, B/P MCL have inferior outcomes and distinct genomic profile, patients with POD12 display a distinct mutation profile and worst prognosis, new therapeutic drugs and clinical trials need to be further explored in B/P MCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal