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1161 Addition of Brentuximab Vedotin to Gemcitabine in Relapsed or Refractory T-Cell Lymphoma: Results of a Lysa Multicenter, Phase II Study. “the TOTAL Trial”

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
Biological, antibodies, Diseases, Non-Biological, Therapies, Non-Hodgkin Lymphoma, chemotherapy, T-Cell Lymphoma, Lymphoid Malignancies
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Olivier Tournilhac, MD, PhD1*, Maya Hacini, MD2*, Kamal Bouabdallah, MD3*, Kamel Laribi, MD4*, Marie Maerevoet, MD5*, Loic Ysebaert, MD, PhD6*, Stephanie Guidez7*, Steven Le Gouill, MD, PhD8,9, Marc André, MD10*, Jehan Dupuis, MD11*, Catherine Thieblemont, MD, PhD12, Emmanuel Bachy, MD, PhD13*, Nicolas Daguindau, MD14*, Franck Morschhauser, MD, PhD15*, Sabine Tricot, MD16*, Pierre Feugier, MD, PhD17*, Anne Banos, MD18*, Thierry Lamy De La Chapelle, MD, PhD19*, Adrien Chauchet, MD20*, Emmanuel Gyan, MD, PhD21, Guillaume Cartron, MD, PhD22*, Hassan Farhat, MD23*, Vincent Camus24*, Bernard Drenou, MD, PhD25*, Hacene Zerazhi, MD26*, David Sibon, MD, PhD27*, Emmanuelle Nicolas-Virelizier, MD28*, Caroline Delette, MD29*, Sylvia Snauwaert, MD30*, Nicole Straetmans, MD31, Richard Delarue, MD32, Marie Parrens, MD33*, Céline Bossard, MD34*, Laurence De Leval, MD35, Philippe Gaulard, MD, PHD36* and Gandhi Laurent Damaj, MD, PhD37

1Service d'Hématologie Clinique et Thérapie Cellulaire, CHU, Université Clermont Auvergne EA7453 Chelter CIC-1405, Clermont-Ferrand, FRA
2Hematologie, Centre Hospitalier Metropole Savoie, Chambery, FRA
3Hematology Clinic, University Hospital of Bordeaux, Pessac, France
4Department of Hematogy, Centre Hospitalier Le Mans, Le Mans, France
5Department of Hematology, Institut Jules Bordet (ULB), Brussels, Belgium
6IUCT-Oncopole, Toulouse, France
7Service d'Hématologie et de thérapie cellulaire, CHU de Poitiers, Poitiers, France
8CRCINA, INSERM, CNRS, Angers University and Nantes University, Nantes, France
9Service d'hématologie clinique, CHU de Nantes, Nantes, France
10Department of Haematology, Université Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium
11Unité Hémopathies Lymphoïdes, AP-HP Hôpital Henri Mondor, Créteil, France
12Hôpital Saint-Louis, Paris, France
13Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite, France
14Hematology Department, CH Annecy Genevois, Annecy, France
15Clinical Hematology Department, Centre Hospitalier Régional Universitaire de Lille, Lille, France
16Service d'Hématologie Clinique, CH de Valenciennes, Valenciennes, France
17Hematology Department, Nancy University Hospital, Vandoeuvre-lès-Nancy, France
18Hematology department, CH Côte Basque, Bayonne, France
19Clinical hematology, University Hospital of Rennes, Rennes, France
20Hematology Department, Besancon University Hospital, Besancon, France
21Centre Hospitalier Universitaire, Service D'Hemaologie Et Therapie Cellulaire, Tours Cedex, France
22CHU Montpellier, Department of Clinical Hematology, Montpellier, France
23Department of Hematology, Hôpital André Mignot, Centre Hospitalier de Versailles, Le Chesnay, France
24Department of Hematology, Centre Henri Becquerel, Rouen, France
25Service d'Hématologie, Groupe Hospitalier de la Région Mulhouse Sud Alsace (GHRMSA), Mulhouse, France
26Clinical Hematology, Avignon Hospital, Avignon, France
27INSERM UMR 1163 & CNRS URL 8254, Hematology Department, Necker University Hospital, APHP, Paris, France, Paris, France
28Centre Leon Berard, Departement d'Oncologie Medicale, Lyon, France
29Oncopole Hopital Sud, Amiens, FRA
30AZ Sint-Jan, Brugge, Belgium
31Hopital de Jolimont, Woluwe Saint Lambert, BEL
32Hematology Department / Hemophilia Center, Necker University Hospital, AP-HP, Paris, France
33Hôpitaux de Bordeaux CHU, Bordeaux, France
34Département de Pathologie, Centre Hospitalier Universitaire de Nantes, Nantes, France
35Hôpital Universitaire de Lausanne, Lausanne, Switzerland
36Department of Pathology and InsermU955, University Hospital Henri Mondor, Créteil, France
37Institut d'Hématologie de Basse-Normandie, CHU de Caen Normandie, Caen, France


Peripheral T-cell lymphoma (PTCL) is a heterogeneous and accounts for approximately 10% of all lymphomas. Outcome of relapse/refractory (R/R) PTCL is poor with median progression-free survival (PFS) and overall survival (OS) of 3 and 6 months in the absence of stem-cell transplantation (SCT). [Mak, JCO, 2013]. Brentuximab vedotin (BV) monotherapy is approved for R/R systemic anaplastic large cell-lymphoma (ALCL) based on 86% overall response rate (ORR) and 57% complete remission (CR). [Pro, JCO, 2012]. In other CD30-positive (CD30+) R/R PTCL, the ORR of BV is 41%. Gemcitabine (G) used as monotherapy in control arm in the randomized phase 3 LUMIERE trial, provided ORR and CR rates of 35 and 22% respectively. [O’Connor, JCO, 2019]. Considering these results we designed a phase 2 study for R/R CD30+ PTCL combining G and BV with the primary end point to increase the ORR by 15%, compared to G monotherapy.

Patients (pts) and Methods:

Pts with histologically confirmed CD30+ (≥5%) PTCL who failed or were refractory to 1-3 prior lines of systemic therapy, with measurable disease and ECOG performance status < 3 were eligible. Pts received an induction of 4 cycles of G-BV (28-days cycles; G: 1000 mg/m² at D1 and D15 plus BV: 1.8 mg/kg at D8). Pts with CR or partial remission (PR) and non-eligible for SCT, received BV maintenance 1.8 mg/kg at D1 (21-days cycles) up to 12 cycles. The primary endpoint was the ORR (CR + PR) according to Lugano criteria based on CT-scan. Secondary objectives included tolerance and safety, DOR, PFS, OS and impact of BV maintenance. Eligible pts were censored at time of SCT. (NCT03496779).


From April 2018 to October 2019, 71 pts were included. Pathology central review according to WHO 2017 criteria, so far available for 50 patients, confirmed angioimmunoblastic T-cell lymphoma (AITL) (22 ; 31%); nodal PTCL-TFH (5 ; 7%); PTCL-NOS (5 ; 7%); ALK- ALCL (10 ; 14.1%) ; ALK+ ALCL (4 ; 5.6%), Enteropathy associated T-cell lymphoma (EATL) (2 ; 2.8%); unclassified PTCL (2 ; 2.8%). There were 47 male and 24 female with a median age of 66 years (20-79) and 17 pts were > 75 years. Median time from diagnosis to enrolment was 9.4 months (range, 6-21). Sixty-five pts (91.6%) presented with stage III-IV. The number of prior lines of therapy were 1 (57 pts), 2 (11 pts) or 3 (3 pts), all pts had received previous CHOP-like chemotherapy, 11 pts previous autologous SCT, 5 pts epigenetic modifiers and 39.4% were refractory to their last line of treatment prior to inclusion. The cut-off date of this analysis was 01/31/2020.

The 4 cycles of G-BV induction were completed in 45 pts (63%). The reasons for early discontinuation were progression (21 pts), death (3 pts) or adverse event (2 pts). In intention-to-treat analysis, the ORR at the end of induction (EOI) was 47.9% including CR (14 pts; 19.7%), PR (20 pts; 28.2%). PET performed in all patients reaching EOI showed overall and complete metabolic responses in 45.1 and 23.9%, respectively. During G-BV induction 58 pts (81.7%) had at least one G > 3 adverse event (AE) including neutropenia (67.2%), thrombopenia (17.2%), infections (15.5%), peripheral neuropathy (PN) (5.2%) and cardiac event (5.2%). Overall PN of any grade was recorded in 8/71 patients (11%) during G-BV induction and caused BV withdrawal in one case.

Among the 34 responding pts after EOI, 27 pts began BV maintenance and 7 pts remain on maintenance at cut-off date. Eight pts were removed from the study due to SCT eligibility, either after the 4 GBV induction (4 pts) or after 1 or 2 maintenance BV cycles (4 pts).

With a median follow-up (FU) of 9.5 (0.5-19.4) months, median PFS is 4.5 months (95%CI [3.5 - 10]) and median OS is 12 months (95%CI [8.6 – NR]). Among the 34 patients in PR/CR after induction, the duration of response (DOR) is 12.8 months (95%CI [10.3 – NR]). At last FU were recorded 32 deaths. Disease status at time of death was PD (25 pts), CR (1 pt) NE or missing (6 pts).

Conclusion :

The addition of BV to G increases the overall response rate by 15% in the treatment of R/R CD30+ PTCL. OS data are encouraging for this overall R/R patient population but PFS is overall short and a longer FU is mandatory. Especially the DOR of pts achieving CR or PR after 4 cycles of G-BV exceeds 1 year on BV maintenance. This combination is generally well tolerated and this study suggests that G-BV combination could be an interesting alternative for R/R CD30+ PTCL.

Disclosures: Tournilhac: Janssen: Consultancy, Honoraria, Other: Travel grant; INNATE Pharma: Consultancy, Honoraria; GILEAD: Consultancy, Honoraria, Other: Travel Grant; ABBVIE: Consultancy, Honoraria, Other: Travle grant; Takeda: Consultancy, Honoraria, Other: Travel grant. Laribi: novartis: Honoraria, Research Funding; amgen: Research Funding; abbvie: Honoraria, Research Funding; takeda: Research Funding. Ysebaert: AbbVie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Guidez: BMS: Honoraria; TAKEDA: Honoraria; Service Hématologie et Thérapie cellulaire CHU POITIERS: Current Employment; AMGEN: Honoraria; CELGENE: Honoraria; JANSEN: Honoraria. Le Gouill: Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. André: Celgene: Other, Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Johnson & Johnson: Research Funding; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Abbvie: Consultancy; Seattle Genetics: Consultancy. Dupuis: Henri Mondor University Hospital Creteil France: Current Employment. Thieblemont: Roche, Amgen, Kyte Gilead, Celgene, Abbvie, Novartis, Cellectis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche, Hospita: Research Funding; Cellectis: Speakers Bureau. Bachy: Beigene: Membership on an entity's Board of Directors or advisory committees; Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria. Morschhauser: Celgene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Servier: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Feugier: janssen: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding. Cartron: F. Hoffmann-La Roche: Consultancy, Honoraria; Abbvie: Honoraria; Jansen: Honoraria; Celgene: Consultancy, Honoraria; Sanofi: Honoraria; Gilead: Honoraria. Camus: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); JANSSEN: Honoraria; AMGEN: Honoraria; PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Sibon: takeda france: Consultancy. Snauwaert: roche: Other: travel; janssen: Other: travel; abbvie: Other. Delarue: BMS: Other: stock options ; Celgene/BMS: Current Employment. De Leval: Abbvie: Honoraria; Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Roche Diagnostics: Honoraria; Lunaphore Technologies SA: Consultancy, Honoraria. Gaulard: CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris: Current Employment; TAKEDA: Consultancy, Honoraria, Research Funding; INNATE PHARMA: Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company).

*signifies non-member of ASH