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Simple Summary: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary T-cell lymphoma of the digestive tract that is characterized by an aggressive clinical course. The aim of this study was to analyze the clinicopathological characteristics and genomic profile of Asian MEITL. In this study, nine cases of Japanese MEITL were analyzed by targeted Next Generation Sequencing and immunohistochemistry and were integrated with previously reported whole-genome copy number microarray-based assay data. All cases showed alterations of the tumor suppressor gene SETD2 and mutations in one or more genes of the JAK/STAT pathway. Therefore, we concluded that the combination of epigenetic deregulation and cell signaling activation may represent a major oncogenic event in the pathogenesis of Asian MEITL, similar to Western MEITL. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary T-cell lymphoma of the digestive tract derived from intraepithelial lymphocytes and characterized by an aggressive clinical course. In this study, nine cases of Japanese MEITL were analyzed by targeted Next Generation Sequencing (NGS) and immunohistochemistry and were integrated with previously reported whole-genome copy number microarray-based assay data. The highlight of our findings is that all cases showed alterations of the tumor suppressor gene SETD2 by mutations and/or loss of the corresponding 3p21 locus. We also demonstrated that all cases showed mutations in one or more genes of JAK/STAT pathway. Therefore, the combination of epigenetic deregulation and cell signaling activation represent major oncogenic events in the pathogenesis of MEITL in Asian MEITL, similar to Western MEITL. [ABSTRACT FROM AUTHOR]

Purpose: Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP)., Methods: This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m 2 , was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria., Results: Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 ( P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% ( P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%)., Conclusion: The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL., Competing Interests: Emmanuel BachyHonoraria: Gilead Sciences, Roche, Amgen, Janssen-CilagConsulting or Advisory Role: Roche, Gilead Sciences, Incyte, TakedaResearch Funding: Amgen Foundation (Inst)Travel, Accommodations, Expenses: Janssen-Cilag, Roche, Gilead Sciences, Incyte Vincent CamusHonoraria: Roche/Genentech, Incyte, Janssen, Gilead Sciences, NovartisConsulting or Advisory Role: RocheResearch Funding: iQone Healthcare (Inst)Travel, Accommodations, Expenses: Pfizer, Roche Catherine ThieblemontHonoraria: Celgene, AbbVie, Bayer, Janssen, Roche, Incyte, Novartis, Gilead SciencesResearch Funding: RocheTravel, Accommodations, Expenses: Roche, Janssen-Cilag, Kite/Gilead, Novartis David SibonConsulting or Advisory Role: Takeda, iQone Healthcare, Janssen, Roche, AbbVieTravel, Accommodations, Expenses: Takeda, Janssen René-Olivier CasasnovasHonoraria: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, AmgenConsulting or Advisory Role: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, IncyteResearch Funding: Roche/Genentech (Inst), Gilead Sciences (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Roche/Genentech, Takeda, Gilead Sciences, Janssen Loïc YsebaertHonoraria: AbbVieConsulting or Advisory Role: AbbVie, Janssen-Cilag, Roche, Gilead SciencesResearch Funding: Roche (Inst), Janssen-Cilag (Inst), Gilead Sciences (Inst) Gandhi DamajConsulting or Advisory Role: Roche/Genentech, Takeda, iQoneResearch Funding: TakedaTravel, Accommodations, Expenses: PFIZEE, Roche/Genentech, AbbVie Stéphanie GuidezConsulting or Advisory Role: Kite/GileadTravel, Accommodations, Expenses: Janssen Marc AndréConsulting or Advisory Role: Takeda, BMSiResearch Funding: Takeda (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Gilead Sciences Alejandro Martín García-SanchoHonoraria: Roche, Janssen-Cilag, Celgene, Servier, Gilead Sciences, TakedaConsulting or Advisory Role: Roche, Celgene, MorphoSys, Kyowa Hakko Kirin, iQone, EUSA Pharma, Gilead Sciences, Novartis, Servier, IncyteExpert Testimony: Gilead SciencesTravel, Accommodations, Expenses: Roche, Celgene¸ Servier Maria Jesus PenarrubiaHonoraria: AbbVie, Celgene, Servier, Takeda, RocheConsulting or Advisory Role: Gilead Sciences, Novartis, Celgene, AbbVie, Takeda, Clinigen GroupResearch Funding: CelgeneTravel, Accommodations, Expenses: Amgen, Servier, Novartis, Janssen, Celgene, Takeda Philipp B. StaberHonoraria: Roche, Amgen, Takeda, Abbott/AbbVie, Janssen Oncology, Incyte, Celgene, Bristol Myers Squibb/Pfizer, MSD Oncology, AstraZenecaResearch Funding: Roche (Inst) Judith TrotmanResearch Funding: BeiGene (Inst), Roche/Genentech (Inst), Pharmacyclics (Inst), Janssen-Cilag (Inst), Takeda (Inst), Celgene (Inst)Travel, Accommodations, Expenses: Roche/Genentech Andreas HüttmannHonoraria: TakedaConsulting or Advisory Role: TakedaTravel, Accommodations, Expenses: Roche Pharma AG Philippe GaulardHonoraria: Takeda, Gilead SciencesConsulting or Advisory Role: TakedaResearch Funding: Takeda (Inst), Innate Pharma (Inst), Sanofi (Inst)Travel, Accommodations, Expenses: Roche Marie-Helene Delfau-LarueHonoraria: Gilead Sciences, AmgenResearch Funding: Roche, CelgeneTravel, Accommodations, Expenses: Mundipharma Laurence de LevalHonoraria: Novartis (Inst)Consulting or Advisory Role: Lunaphore Technologies (Inst), Bayer (Inst) Michel MeignanHonoraria: RocheTravel, Accommodations, Expenses: Roche Ju LiEmployment: Bristol Myers Squibb/CelgeneStock and Other Ownership Interests: Bristol Myers Squibb/CelgeneResearch Funding: Bristol Myers Squibb/CelgeneTravel, Accommodations, Expenses: Bristol Myers Squibb/Celgene Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Richard DelarueEmployment: Celgene/Bristol Myers Squibb, BeiGeneStock and Other Ownership Interests: Celgene/Bristol Myers Squibb, BeiGeneNo other potential conflicts of interest were reported.