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2081 Nivolumab in Combination with Gemcitabine and Oxaliplatin (GemOx) in Relapse/Refractory T-Cell Lymphoma: Preliminary Results of the Experimental Arm of the Niveau Trial

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
Biological, Diseases, Non-Biological, Therapies, checkpoint inhibitors, chemotherapy, T-Cell Lymphoma, Lymphoid Malignancies
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Roch Houot, MD, PhD1*, Viola Poeschel, MD2*, Bettina Altmann, PhD3*, Thomas Illmer, MD4*, Marc André, MD5*, Martin Dreyling, MD6, Herve Maisonneuve, MD7, Herve Tilly, MD, PhD8, Stephanie Mayer, MD9*, Rene-Olivier Casasnovas, MD10*, Steven Le Gouill, MD, PhD11, Fritz Offner, MD, PhD12, Guillaume Cartron, MD, PhD13*, Andrea Kerkhoff, MD14*, Thomas Weber, MD15*, Joerg Hoffmann, MD16*, Marita Ziepert, PhD3*, Wolfram Klapper, MD17*, Emmanuel Itti, MD, PhD18*, Dirk Hellwig19*, Laurence De Leval, MD20, Andreas Rosenwald, MD21*, Corinne Haioun, MD, PhD22*, Laurent Dercle, MD23*, Philippe Gaulard, MD, PhD24* and Gerhard Held, MD2*

1Hematology Department, CHU Rennes, Rennes, France
2Department of hematology, oncology and rheumatology, Saarland University Medical School, Homburg/Saar, Germany
3Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, IMISE, Leipzig, Germany
4Hematology-Oncology Practice, Dresden, Germany
5Department of Hematology, CHU UCL Namur - Site Godinne, Yvoir, Belgium
6Department of Medicine III, Klinikum Der Universitaet Muenchen-Campus Grosshadern, Munich, Germany
7Clinical Hematology, Centre Hospitalier Départemental Vendée, La Roche-sur-Yon, France
8Centre Henri Becquerel, Rouen, France
9Innere Medizin III, Universitätsklinikum Regensburg, Regensburg, Germany
10Hématologie Clinique and INSERM 1231, CHU Dijon, Dijon, France
11Service d’hématologie clinique du CHU de Nantes, INSERM CRCINA Nantes-Angers, NeXT Université de Nantes, Nantes, France
12University Hospital Ghent, Gent, Belgium
13Centre Hospitalier Universitaire de Montpellier, Montpellier, France
14Department of Medicine A, University Hospital Muenster, Muenster, Germany
15Department of Medicine IV, Hematology and Oncology, University Hospital Halle, Halle, DEU
16Hämatologie, Onkologie und Immunologie, Philipps Universität Marburg, Marburg, Germany
17Department of Hematopathology, University of Schleswig-Holstein, Campus Kiel, Kiel, Germany
18Service de médecine nucléaire, CHU Henri Mondor, Creteil, FRA
19Department of Nuclear Medicine, University Hospital Regensburg, Regensburg, Germany
20Hôpital Universitaire de Lausanne, Lausanne, Switzerland
21Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany
22Lymphoid Malignancies Unit, Henri Mondor University Hospital, APHP, Créteil, France
23Columbia University, New York City, NY
24Department of Pathology, Henri Mondor Hospital, APHP, Paris Est-Créteil (UPEC) University Faculty, INSERM UMR-S 955, Créteil, France


Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphomas, which usually carry a poor prognosis. Malignant T-cells may overexpress programmed death ligand 1 (PD-L1), which signals via programmed death-1 (PD-1) receptor, and provides an inhibitory signal on normal T-cells further suppressing antitumor immunity. They can also express PD1 which may act as a tumor suppressor on malignant T-cells (Wartewig et al, Nature 2017). Thus, blocking the PD1/PDL1 synapse in PTCL may lead to tumor regression or progression.

The NIVEAU trial is an ongoing international, multicenter, randomized, open label, phase 3 study testing Nivolumab (Nivo) in combination with (Rituximab), Gemcitabine, Oxaliplatin ((R-)GemOx) for patients with aggressive (B and T-cell) Non-Hodgkin Lymphoma in first relapse or progression not eligible for High-Dose Chemotherapy (NCT03366272). Here, we performed a preliminary analysis of the experimental arm (Nivo-GemOx) of the PTCL cohort to assess the safety and efficacy of this regimen in this population.


Key eligibility criteria include: first relapse or progression of peripheral T-cell lymphoma (PTCL), ineligibility for high dose therapy (defined as >65 years of age or older than 18 years if HCT-CI score > 2), only one prior chemotherapy regimen including an anthracycline. Pts were planned to receive 8 cycles Nivolumab (3mg/kg) plus Gemcitabine and Oxaliplatin in 2-wk intervals followed by additional 18 Nivolumab (3mg/kg) biweekly as consolidation or until progression. Response was evaluated after 4 and 8 cycles of GemOx. Each progression/relapse of PTCL had to be reported as a SAE.


The analysis (data cut-off 13-July-2020) included 12 PTCL pts enrolled in the experimental arm (Table 1): 4 (33%) PTCL NOS, 3 (25%) AITL, 1 (8%) PTCL TFH-type, 2 (17%) ALCL ALK-, 1 (8%) EATL, and 1 (8%) MEITL. Median age was 69.5 years (range, 53-80), 7 (58%) patients were male, 2 (17%) had received a prior autologous stem cell transplantation, and 5 (42%) were refractory to first line therapy. At enrollment, performance status was 0-1 in 9 (75%) pts and 2 in 3 (25%) pts, 11 (92%) had Ann Arbor stage III-IV, 2 (17%) had B-symptoms, 7 (58%) had more than one extra-nodal site and 4 (33%) had elevated LDH. PD1 and PD-L1 were expressed by the tumor cells in 6/10 (60%) and 2/11 (18%) patients, respectively (Table 1). Pts have received a median of 6 (1-8) cycles of GemOx and 7 (1-26) infusions of nivolumab. Treatment was prematurely discontinued in 9 pts (7 during induction and 2 during consolidation), due to lymphoma progression (n=6), toxicity (n=2) and an intercurrent disease (n=1). There were 26 SAE in 10 patients, including 8 progressive diseases. Nine (75%) patients achieved an objective response (4 CR and 5 PR). Two patients (pt 9: MEITL PD1-negative; and pt 12: PTCL-NOS strongly PD1-positive) experienced primary progression upon Nivo-GemOx (Table 1). Median PFS2 (time from randomisation to 2nd rel/prog/death) was 6.9 months (95% CI: 1.9-11.9) vs 7.7 months (95% CI: 7.2-8.2) for PFS1 (time from diagnosis to 1st rel/prog). PFS2 was superior to PFS1 in 2 out of 8 patients (25%), and not informative in 4 pts: 3 who are still on therapy (ongoing PFS) and 1 who died prematurely due to infection (pt 8) (Figure 1). Median OS was 24.8 months (95% CI: 0-49.8). After a median follow-up of 22.8 months, 7 patients have died (5 from lymphoma and 2 from infection (1 COVID-19 infection and 1 yeast septicemia)), and 5 remain alive.


Nivolumab in combination with GemOx was well tolerated in PTCL. The response rate and PFS2 (compared to PFS1) are encouraging. Marked differences in PFS2 might reflect heterogeneity of biology and susceptibility to PD-1 blockade in combination with GemOx chemotherapy. Furthermore, the translational research program of the study might help to identify markers which are predictive for efficacy of PD-1 blockade in PTCL. This phase 3 trial is actively enrolling patients and an update of these results will be presented at the meeting.

Disclosure: ISR financially supported by Bristol Myers Squibb.

Disclosures: Houot: Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Kite: Honoraria; Gilead: Honoraria; MSD: Honoraria; Bristol-Myers Squibb: Honoraria. Poeschel: Roche: Other: Travel, Accommodations, Expenses; Amgen: Other: Travel, Accommodations, Expenses; Abbvie: Other: Travel, Accommodations, Expenses. André: Abbvie: Consultancy; Celgene: Other, Research Funding; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Takeda: Consultancy; Bristol-Myers-Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Karyopharm: Consultancy; CHU UCL Namur, site Godinne, Yvoir, Belgium: Current Employment; Seattle Genetics: Consultancy; Gilead: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Johnson & Johnson: Research Funding; Novartis: Consultancy, Research Funding; Amgen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Dreyling: Beigene: Consultancy; Bayer: Consultancy, Speakers Bureau; Astra Zeneca: Consultancy; Abbvie: Research Funding; Roche: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau. Tilly: BMS: Honoraria. Casasnovas: Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Amgen: Consultancy, Honoraria; MSD: Consultancy, Honoraria. Le Gouill: Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Cartron: Celgene: Consultancy, Honoraria; Gilead: Honoraria; Abbvie: Honoraria; Jansen: Honoraria; Sanofi: Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria. Kerkhoff: BMS: Honoraria. De Leval: Lausanne University Hospital & Lausanne University Institute of Pathology: Current Employment; Lunaphore Technologies SA: Consultancy, Honoraria; Abbvie: Honoraria; Roche Diagnostics: Honoraria. Gaulard: takeda: Honoraria, Research Funding; innate pharma: Research Funding. Held: Roche: Consultancy, Other: travel grants, Research Funding; MSD: Consultancy; Acrotech, Spectrum: Research Funding; Amgen: Research Funding; BMS: Consultancy, Other: Travel Grants, Research Funding.

OffLabel Disclosure: Nivolumab in peripheral T-cell lymphoma

*signifies non-member of ASH