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232 Nivolumab First-Line Therapy for Elderly, Frail Hodgkin Lymphoma Patients: Niviniho, a Lysa Phase II StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Hodgkin Lymphoma Clinical Trials
Hematology Disease Topics & Pathways:
Clinical Trials, Hodgkin Lymphoma, Biological, Lymphomas, Non-Biological, Clinical Research, Chemotherapy, Elderly, Checkpoint Inhibitor, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, Study Population
Saturday, December 11, 2021: 2:45 PM

Julien Lazarovici, MD1*, Sandy Amorim, MD2*, Krimo Bouabdallah3*, Stéphanie Guidez, MD4*, Lysiane Molina, MD5*, Franck Morschhauser, MD, PhD6*, Anne-Claire Gac, MD7*, Thomas Gastinne, MD8*, Kamel Laribi, MD9*, Vincent Launay, PhD, MD10*, Bohrane Slama, MD11*, Nawel Belmecheri, MD12*, René-Olivier Casasnovas, MD13*, Anne Corby, MD14*, Eric Durot15*, Pierre Feugier, MD, PhD16*, Emmanuelle Nicolas-Virelizier, MD17*, David Sibon, MD, PhD18*, Alina Berriolo-Riedinger, MD19*, Veronique Edeline, MD20*, Thierry Vander Borght, MD, PhD21*, Diane Damotte, MD, PhD22*, Alexandra Traverse-Glehen, MD, PhD23*, Marc Andre, MD24* and Vincent Ribrag, MD25

1Department d'Hématologie, Gustave Roussy Cancer Campus Grand Paris, Villejuif CEDEX, France
2Hématologie clinique, Hôpital Saint Vincent de Paul, Lille, France
3Service d'Hématologie et Thérapie cellulaire, CHU Bordeaux, Hôpital Haut-Lévêque, Pessac, France
4Service d'Hématologie et de Thérapie cellulaire, CHU de Poitiers, Poitiers, France
5Hématologie clinique, CHU de Grenoble, La Tronche, France
6Service des Maladies du Sang, CHU de Lille, Hôpital Huriez, Lille, France
7Institut d'Hématologie de Basse-Normandie, CHU de Caen, Caen, France
8Service d'Hématologie clinique, CHU Nantes, Nantes, France
9Département d'Hématologie, CH Le Mans, Le Mans, France
10CH de Saint-Brieuc, Hôpital Yves Le Foll, Saint-Brieuc, France
11Service d'Oncologie médicale et d'Hématologie clinique, CH d'Avignon, Avignon, France
12Service d'Hématologie, Institut Paoli Calmettes, Marseille, France
13Hématologie clinique, CHU Dijon Bourgogne, Dijon, France
14Service d'Hémato-Oncologie, CH de La Rochelle, La Rochelle, France
15Service d'Hématologie, saint louis, Reims Cedex, France
16Département d'Hématologie, CHRU Nancy, Hôpitaux de Brabois, Vandoeuvre-lès-Nancy, France
17Service d'Hématologie, Centre Léon Bérard, Lyon, France
18Service d'Hématologie, APHP, Hôpital Necker, Paris, France
19Département de Médecine nucléaire, Centre Georges François Leclerc, Dijon, France
20Département d'Imagerie médicale, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France
21CHU UCL Namur, Yvoir, BEL
22Département de Pathologie, APHP, Hôpital Cochin, Paris, France
23Service d'Anatomie pathologique, Université Lyon 1/Centre Hospitalier Lyon Sud, Pierre Bénite, France
24Service d'Hématologie, CHU UCL Namur, Yvoir, Belgium
25Département d'Hématologie, Gustave Roussy Cancer Campus, Villejuif, France

Background

In contrast to the high cure rates in young patients (pts) treated with anthracycline-based chemotherapy, classical Hodgkin lymphoma (cHL) prognosis is poor in elderly pts, and very few data exist for pts considered too frail to receive standard-dose chemotherapy. In those patients, limited therapeutic options are available. Among the new immune-oncology drugs, Nivolumab, an anti-PD1 antibody, has demonstrated high response rate and very good tolerance, and is now approved in relapse and refractory (R/R) cHL. However, data on its use in the frontline setting are scarce.

Material and methods

We designed a prospective, open-label, multi-centric phase II study, to assess the efficacy and safety of nivolumab alone, or in combination with vinblastine in naive pts aged 61 years and older, with cHL and coexisting medical conditions. Pts were eligible if they had a Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of 6 or more.

Treatment consisted in an induction phase of 6 nivolumab injections, delivered at a flat dose of 240 mg every 14 days. Early assessment was done at 12 weeks by PET-CT and CT-scan. Pts who achieved complete metabolic response (CMR) at early assessment completed treatment with nivolumab monotherapy for 18 additional cycles (consolidation phase). Pts who obtained partial metabolic response (PMR) or non metabolic response (NMR, stable disease) received a combination of 18 cycles of nivolumab plus vinblastine, administered intravenously.

The primary objective of the study was to assess the CMR rate based on central review at the end of treatment (EOT).

Results

From August 30th, 2018 to April 28th, 2020, 64 pts were included in 31 centers, which composed the full analysis set (FAS), used for safety evaluation. Among these 64 pts, 56 pts were fully evaluable and constituted the efficacy set (ES) used for the efficacy analysis (8 pts progressed early or were not assessed by PET-CT).

The median age at inclusion in the ES was 75 years [range: 62-91]. Patients had a median CIRS-G score of 10 [range: 6-18] at baseline, and a median G8 score of 12.5 [range: 6-17]. Seventy-three percent of pts had a stage III-IV disease and 42.9% of pts had B symptoms. At EOT, 16 pts (28.6%) achieved CMR according to central PET-CT review. Ten pts (17.9%) achieved PMR, 10 pts were in NMR (17.9%) and progressive metabolic disease was observed in 17 pts (30.4%). Three pts were not evaluated. The overall response rate at end of induction was 51.9%, (9 CMR and 18 PMR). 23 pts received a consolidation with nivolumab and vinblastine. With a median follow-up of 20.1 months, median PFS was 9.8 months [95% CI: 4.2;12].

15/64 pts of the FAS died during treatment (23.4%): 6 pts from lymphoma, 2 pts from toxicity of study treatment and 2 pts from concurrent illness. One patient died from toxicity of additional treatment after progression, and 4 pts from other causes. The 2-year overall survival was 76.7% [95% CI: 59.6;87.3]. 49/64 pts (76.6%) experienced at least one AE, among which 32 pts experienced grade 3-4 AEs. The 3 more frequent grade 3-4 AEs were neutropenia (8 pts), sepsis (7 pts) and respiratory tract infection (5 pts). Adverse events were related to nivolumab in 36 pts and led to treatment discontinuation in 19 pts (29.7%). Adverse events of special interest i.e., immune-related AEs, were recorded in 22 pts, including 3 pneumonitis, 1 myocarditis, 1 encephalitis and 1 colitis.

Among the 64 pts of the FAS, 34% of pts completed the treatment. The median number of cycles administered was 7 [range: 1-24] for nivolumab and 17 [range: 1-18] for vinblastine.

Conclusion

The NIVINIHO study is the first study to assess the efficacy and safety of an immune checkpoint inhibitor for first line therapy in elderly, frail patients with cHL. The results suggest that in this setting, a nivolumab-based therapy is active in a subset of pts. Further studies and biological analysis are planned to determine which patients may benefit from this approach.

Disclosures: Lazarovici: Mundipharma: Other: Travel grant. Bouabdallah: Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Sandoz: Consultancy, Honoraria; Abbvie: Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Morschhauser: Chugai: Honoraria; Janssen: Honoraria; AstraZenenca: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genmab: 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; Genentech, Inc.: Consultancy; Servier: Consultancy; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gastinne: Gilead/kyte: Honoraria; Takeda: Honoraria. Laribi: Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; BeiGene: Other: Personal Fees; Le Mans Hospital: Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Jansen: Research Funding. Feugier: Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Sibon: iQone: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy. Ribrag: Gilead: Membership on an entity's Board of Directors or advisory committees; PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; GSK: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: Nivolumab. Presently labelled for relapse and refractory classical Hodgkin lymphoma and other malignancies

*signifies non-member of ASH