Monomorphic epitheliotropic intestinal t-cell lymphoma (meitl): clinico-pathological analysis of a multicenter european cohort

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive primary intestinal T-cell lymphoma. Most case series were reported in Asia. Here we present a detailed clinico-pathological analysis of a European cohort. Methods: Fourty-nine patients (pts) diagnosed with MEITL between 2005 and 2020 were retrived from 42 LYSA centers in France, Belgium and Switzerland. Pathology was reviewed and confirmed in all cases, complete immunophenotypic profiles were generated, and mutation status of 27 relevant genes was obtained by targeted or whole exome sequencing in 44 cases. Clinical, imaging, and survival data were collected. Results: Median age was 69y (29-91), 55% were men. Among 34 pts with anamnestic information: one carried a diagnosis of coeliac disease, screening for coeliac disease was negative in 12/12 pts tested. 30 pts (88%), presented with abdominal emergency (bowel perforation n = 23 and/or obstruction n = 11). B symptoms, cytopenia and inflammation were found in 65% (n = 22), 41% (n = 14) and 94% (n = 32). FDG-PET/CT showed hypermetabolic lesions with a high SUVmax (8 to 30). On the whole cohort of 49 pts : intestinal involvement distribution was small bowel (n = 47), large bowel (n = 7), anal (n = 1) and stomach (n = 1). Multifocal intestinal involvement was seen in 9 pts. The Ann Arbor stage was I E (n = 15), II E (n = 11), and IV (n = 15), missing data (MD) (n = 8). In the 49 pts, the phenotype was CD2+ (51%) CD3+ (98%) CD4- (94%) CD5- (96%) CD7+ (98%) CD8+ (88%) CD56+ (90%) CD103+ (91%) CD79a- (90%) EBER- (98%) with activated cytotoxic profile. CD30 and aberrant CD20 expression were detected in 0% and 23%. TCR was γδ (n = 20), αβ(n = 5), double positive (n = 5) or double negative (n = 11). SETD2 was mutated (n = 38), deleted (n = 9) or both (n = 6) and 38/42 showed defective H3K36 trimethylation. Other frequent mutations included STAT5B (n = 27), JAK3 (n = 22), TP53 (n = 14). A 1st line chemotherapy (CT) was recorded in 28 pts including 24 CHOP-like and 4 autologous transplant, 15 did not receive any CT (MD = 9). Following 1st line, 9 pts reached a CR, and 13 had primary progression or insufficient response (MD = 6). All salvaged pts eventually died from progression or toxicity. Conclusion: In this large European cohort of MEITL, we expand the extremely poor prognosis related both to the complexity of clinical presentation and to primary resistance to CHOP-like polychemotherapy, with a negative impact of single and double-hit mutations of TP53 and STAT5B. Dynamic management including post-operative supportive care, chemotherapy attempt and potential consolidation by auto- or even allograft is crucial. Keywords: Aggressive T-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.