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136 The Eatl-001 Trial: Results of a Phase 2 Study of Brentuximab Vedotin and CHP Followed By Consolidation with High-Dose Therapy - Autologous Stem-Cell Transplantation (HDT-ASCT) in the Frontline Treatment of Patients with Enteropathy-Associated T-Cell Lymphoma

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: T/NK Cell Lymphoma Frontline Clinical Trials
Hematology Disease Topics & Pathways:
Clinical Trials, Biological, Antibody Therapy, Lymphomas, Non-Biological, Clinical Research, Chemotherapy, Clinically Relevant, T Cell Lymphoma, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, Monoclonal Antibody Therapy, Transplantation
Saturday, December 11, 2021: 12:45 PM

David Sibon, MD, PhD1*, Sherine Khater, MD2*, Julie Bruneau, MD, PhD3*, Chantal Brouzes, MD4*, Ludovic Lhermitte, MD, PhD4*, Thierry Jo Molina, MD, PhD3*, Guillaume Cartron, MD, PhD5*, Veronique Morel, MD6*, Georgia Malamut, MD, PhD7*, Adrien Chauchet, MD8*, Franck Morschhauser, MD, PhD9*, Baptiste Perard, MD10*, Jean-Michel Boulet, MD11*, Anne-Cécile Gauchy, MD12*, Nadine Cerf-Bensussan, MD, PhD13*, Elizabeth A. Macintyre, PhD, MD4, Vahid Asnafi, MD, PhD4*, Christophe Cellier, MD, PhD2* and Olivier Hermine, MD, PhD1*

1Hematology Department, Necker University Hospital, Paris, France
2Department of Gastroenterology, HEGP University Hospital, Paris, France
3Pathology Department, Necker University Hospital, Paris, France
4Laboratory of Onco-Hematology, Necker University Hospital, Paris, France
5Hematology Department, Montpellier University Hospital, Montpellier, France
6Hematology Department, Pitié Salpétrière University Hospital, Paris, France
7Department of Gastroenterology, Cochin University Hospital, Paris, France
8Hematology Department, Besançon University Hospital, Besançon, France
9Hematology Department, Lille University Hospital, Lille, France
10Hematology Department, Centre Hospitalier de la Côte Basque, Bayonne, France
11Oncology and Hematology Department, Polyclinique de Blois, La Chaussée Saint-Victor, France
12Hematology Department, Reims University Hospital, Reims, France
13INSERM UMR1163, Laboratory of Intestinal Immunity, Imagine Institute, Paris, France

Background

Enteropathy-associated T-cell lymphoma (EATL), previously designated type 1 EATL, is a neoplasm of intraepithelial T cells that occurs in individuals with celiac disease (CD). It is a rare lymphoma, accounting for approximately 3% of all peripheral T-cell lymphomas (PTCLs). EATL may be preceded by refractory CD (RCD), defined as persistent or recurrent symptoms and signs of malabsorption with villous atrophy despite a strict gluten-free diet for more than 12 months. Currently, RCD is categorized into 2 types, based on immunophenotypic and molecular criteria. In RCD-II, intraepithelial lymphocytes (IELs) have an aberrant phenotype and a clonal TCR gene rearrangement. RCD-II is considered a low-grade lymphoma of intraepithelial T cells, with a high risk of transformation into EATL. CD or RCD may be diagnosed prior to or concomitant with EATL.

EATL has a poor prognosis due to perforation or obstruction of the bowel, sepsis, malnutrition and treatment resistance, with 2-year OS of 20% (de Baaij, CCR 2015). An EATL prognostic index (EPI) has been developed, that can distinguish 3 risk groups (de Baaij, CCR 2015).

Optimal treatment of EATL is an unmet need, and novel therapeutic approaches are required. Most EATLs are CD30+ and could be targeted by brentuximab vedotin (BV). Based on the encouraging activity and manageable safety profile of BV and CHP (cyclophosphamide, doxorubicin and prednisone) combination in CD30+ PTCLs, the EATL-001 phase 2 trial was initiated to assess the efficacy and safety of BV-CHP followed by HDT-ASCT for the frontline treatment of patients (pts) with EATL (ClinicalTrials.gov No. NCT03217643). Here we report the first results of the EATL-001 trial.

Methods

EATL-001 is an Investigator Initiated-Sponsored Research phase 2 study, on behalf of the CELAC (French NCI-labeled network of Centers of Expertise for Lymphomas Associated with Celiac disease). Key inclusion criteria were as follows: Newly diagnosed CD30+ (≥10% of neoplastic cells by central review) EATL (WHO 2016 criteria), 18-65 years, PS 0-3. Response was assessed according to the Lugano classification. Pts were scheduled to receive 4 cycles of BV+CHP as induction. Responding pts received 2 cycles of Etoposide (200 mg/m2) + Methotrexate (3 g/m2) followed by HDT-ASCT (BEAM conditioning regimen). The primary endpoint was 2-year PFS per investigator. Underlying CD/RCD diagnosis was based on uninvolved duodenal histology (including CMF and TCR gene rearrangement analysis of IEL), serology and HLA typing.

Results

A total of 14 pts were included between February 2018 and February 2021. The median age was 54 years (range, 34-65) and 64% were male. 11 pts (79%) had initial surgery for bowel obstruction (n=6) or jejunal perforation (n=5). All pts had CD, diagnosed prior to (n=4) or concomitant with (n=10) EATL. 9 pts (64%) had RCD-II. CD30 expression ranged from 10% to 100%, nine cases having 100% positivity. EPI was high-risk in 4 pts (29%), intermediate-risk in 6 pts (43%), and low-risk in 4 pts (29%).

Preliminary results by investigator assessment show an overall response rate following completion of the induction of 79% (11/14) with 64% (9/14) achieving a complete response. 3 pts had primary progressive disease (all had high-risk EPI), of which 2 died of the lymphoma. The 11 responding pts, still in response before intensification, underwent HDT-ASCT. 2 pts died of septic shock during HDT-ASCT. With a median follow-up of 2.1 years, there was no relapse and the 2-year PFS and OS for all pts were 63% and 68%, respectively.

The incidence of AEs was consistent with the known safety profiles of BV-CHP regimen.

Conclusions

EATL-001 is the first prospective phase 2 study dedicated to EATL. BV-CHP was well tolerated and induced high response rates, allowing the majority of patients to be transplanted. This novel therapeutic approach shows promising efficacy compared to historical controls.

Disclosures: Sibon: Takeda: Consultancy; Roche: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; iQone: Consultancy. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Morschhauser: Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; AstraZenenca: Membership on an entity's Board of Directors or advisory committees. Hermine: Takeda: Consultancy.

OffLabel Disclosure: Brentuximab vedotin is not approved in Europe for EATL.

*signifies non-member of ASH