TP53 Mutations Identify High-Risk Peripheral T-Cell Lymphoma Patients Treated with CHOP-Based Chemotherapy

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1367-1367
• Main Authors: Johnson, William T., Ganesan, Nivetha, Epstein-Peterson, Zachary D., Maccaro, Catherine, Galasso, Natasha, Sauter, Craig S., Neuman, Rachel, Khan, Niloufer, Moskowitz, Alison J., Dogan, Ahmet, Horwitz, Steven M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-151779

Introduction Mutational profiling in peripheral T-cell lymphoma (PTCL) is increasingly used to aid in diagnosis (Wang. Blood 2015), predicting response (Ghione. Blood Adv 2020), and prognosis (Watatani. Leukemia 2019). However, many analyses lack details of upfront treatment and survival outcomes. The Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) is a custom hybridization capture-based assay encompassing the protein-coding exons of >400 targeted genes (Cheng. J Molec Diag 2015). Using the MSK-IMPACT data generated from a large TCL patient (pt) population (N=396), we sought alterations which may predict resistance to or high rates of relapse after CHOP-based chemotherapy. Methods PTCL pts with MSK-IMPACT were detected in the CBioPortal online platform. We included histologies treated with curative intent CHOP-based induction +/- autologous stem cell transplant (ASCT). This included PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), PTCL with a T-follicular helper phenotype (FH-TCL), ALK+ and ALK- anaplastic large cell lymphoma (ALCL), and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Univariate analysis (UVA) for PFS and OS based on the presence of recurring genetic alterations was done using Cox proportional hazard regression analysis. Mutations (mut) assessed included TET2, DNMT3A, RHOA, IDH2, TP53, FAT1, STAT3, STAT5B, JAK1, SETD2, and copy number alterations (CNA) in TP53 and CDKN2A. Comparisons of survival curves were performed by log-rank test. As many pts were sequenced at relapse, to minimize bias, relevant findings were confirmed in the smaller set of pts sequenced at diagnosis and/or before relapse (prospective cohort). Results In total, 131 pts met inclusion criteria and had >1 MSK-IMPACT. One pt with a 49-gene panel was also included (N=132). The prospective cohort had 73 (55%) pts. Histologies were PTCL-NOS (N=36, 27%), AITL (N=62, 47%), FH-TCL (N=9, 7%), ALK-ALCL (N=15, 11%), ALK+ALCL (N=6, 5%), and MEITL (N=4, 3%). Regimens were CHOP + etoposide (N=59, 45%), CHOP (N=40, 30%), brentuximab + CHP (N=15, 11%), other CHOP-based (N=18, 14%). The most frequent mut were TET2 (N=69, 52%), RHOA (N=40, 30%), DNMT3A (N=25, 19%), TP53 (N=21, 16%), and IDH2 (N=15, 11%), and for CNA were losses of TP53 (N=9, 7%) and CDKN2A (N=9, 7%). TET2 mut were most frequent in AITL (N=51, 82%), FH-TCL (N=6, 67%), and PTCL-NOS (N=10, 28%). RHOA mut were found in 2 cases