Brentuximab Vedotin (BV) and Nivolumab (nivo) for Untreated Patients with Hodgkin Lymphoma (HL): Long-Term Results

Background: Whereas major improvements have been made in the treatment of advanced HL outcomes of patients > 60 yrs are generally suboptimal compared with younger patients, and generally with more toxicity. To address this issue we conducted the first phase II study of BV-nivo in older pts with HL (ACCRU RU0515051, NCT02758717), with initial results reported at a median of 20.2 mo of follow-up. (Cheson et al, Lancet Haem, 11:e808, 2020). Herein we present the 5-year follow-up for this study.

Methods: Eligible pts were either >60 yrs or considered unsuitable for standard chemotherapy because of cardiac, pulmonary or renal dysfunction. Pts received BV at 1∙8 mg/kg (dose cap at 180 mg) and nivo at 3 mg/kg both intravenously every 21 days for 8 cycles.The primary endpoint was overall response rate (ORR).

Results: Follow-up data were available for 39 of the original 46 pts. At a median follow-up of 58.5 months (0.45-65.4 mo), the median duration of response was 17.2 mo (11.6-45.2). 58.7% of the patients had progressed with the median progression-free survival of 18.3 mo (12.8-46.3 mo); thus 41.3% had still not experienced a progression event. Median overall survival was not yet reached with 84.8% of patients still alive.

Conclusions: BV-nivo is an effective regimen for patients >60 yr, curing approximately 40% of pts. For those not cured by initial therapy, outcome with subsequent treatment is excellent, suggesting check point inhibitor sensitization, or other factors. Optimization of dose and schedule, and incorporation of other novel agents will result in a successful chemo-free approach for older patients with HL, especially those unable to receive an anthracycline.

Cheson:Adaptive Biotechnologies: Consultancy; AbbVie: Consultancy; Ipsen: Consultancy; Genmab: Consultancy; Merck: Consultancy; Symbio Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Imaging Endpoints: Consultancy; Calyx: Consultancy; Beigene: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Clearview: Consultancy; Incyte: Speakers Bureau; Center for Cancer and Blood Disorders: Current Employment. Bartlett:Celegne: Research Funding; Forty Seven: Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Foresight Diagnostics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Washington University School of Medicine: Current Employment; Janssen: Research Funding; Millennium: Research Funding; BMS: Research Funding; Autolus: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Gilead: Research Funding; Kite Pharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lee:Oncternal: Consultancy, Research Funding; Takeda: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Curio: Honoraria; MJH: Honoraria; BMS: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Advani:Cyteir: Research Funding; Autolus: Honoraria, Other: DSMB/Advisory Boards; Regeneron: Research Funding; Gilead: Research Funding; Merck: Other: Steering committee, DSMB/Advisory Boards, Research Funding; ADCT: Honoraria, Other: DSMB/Advisory Boards; Seattle Genetics: Research Funding; BeiGene: Honoraria, Other: DSMB/Advisory Boards, Research Funding; Roche/Genentech: Honoraria, Other: Steering committee, DSMB/Advisory Boards, Research Funding. Christian:Millenium: Research Funding; Genentech: Research Funding; Astra Zeneca: Honoraria; Ipsen: Honoraria; Acerta: Research Funding; Bristol Myers Squibb: Research Funding. Diefenbach:FATE Therapeutics: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Millenium: Research Funding; Merck: Consultancy, Research Funding; Gilead: Current equity holder in publicly-traded company, Research Funding; Genmab: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; I MAB: Consultancy, Current equity holder in private company; NYU Grossman School of Medicine/Perlmutter Cancer Center at NYU Langone Health: Current Employment; OverT Therapeutics: Current equity holder in private company; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding. Feldman:Genomic Testing Cooperative: Current equity holder in private company; ADCT: Consultancy, Honoraria, Research Funding; Alexion: Research Funding; Astrazeneca: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Trillium: Research Funding; TESSA: Research Funding; Corvus: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria; Kymera: Research Funding; DAIICHI: Research Funding; Merck: Research Funding; Portola: Research Funding; Genmab: Consultancy, Honoraria, Research Funding, Speakers Bureau; Epizyme: Consultancy, Honoraria; BMS: Consultancy, Research Funding; OMI: Current equity holder in private company. Ansell:Bristol Myers Squibb: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; SeaGen: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding; ADC Therapeutics: Research Funding; AstraZeneca: Research Funding.

Both brentuximab vedotin and nivolumab are approved for patients with Hodgkin lymphoma; however, this combination in the front-line has not yet been approved