Phase 2 trial of nivolumab plus adriamycin, vinblastine, dacarbazine (n‐avd) as frontline therapy in older adults with hodgkin lymphoma

Background: Outcomes of classical Hodgkin lymphoma (cHL) remain poor in older adults (OA) with 5- year progression free survival (PFS) of 60% even with curative therapy (Cheng, et al. Blood Advances 2022). In the ECHELON-1 study, brentuximab-AVD led to higher incidence of toxicities in OA without any significant benefit in PFS compared to ABVD (Evens, et al. Haematologica 2022). The CheckMate 205 study established the safety of nivolumab plus doxorubicin, vinblastine and dacarbazine (N-AVD), however it included only 6 patients (pts) ≥60 years (y) of age (Ramchandren, et al. JCO 2019). We conducted a multicenter, investigator-initiated, phase 2 trial to evaluate the safety and efficacy of N-AVD specifically in OA with cHL, and to understand the impact of baseline geriatric assessment (GA) on treatment toxicity in this vulnerable population. Methods: Pts ≥ 60y with newly diagnosed, any stage, cHL were treated with 6 cycles of AVD at standard doses plus nivolumab 240 mg intravenously on days 1 and 15 of each cycle. A GA was performed prior to therapy initiation that included measures of function, comorbidity, cognition, psychological state, social activity/support, and nutritional status. The primary end point was 2-year PFS. We hypothesized that N-AVD would improve the 2-year PFS for OA with cHL from a historical control of 55% (Evens, et al. BJHaem 2013) to 75%. Secondary end points included 2-year overall survival (OS) and safety. The mean scores of each domain of the GA were corelated with grade ³3 toxicities using logistic regressions. Results: 37 pts enrolled; 33 are evaluable for response (4 too early). Median age was 66 y (range 60–78) with 41% pts ≥70 y. At diagnosis, 78% pts had stage 3/4 disease, 68% had International Prognostic Score of ≥3, 54% had B symptoms and 43% had extranodal disease. Overall and complete response rates were 100% and 97% respectively, one patient had a partial response with biopsy being non-diagnostic. At a median follow-up of 37 months, 5 (14%) pts had HL relapse, and one pt died from HL. The 2 y PFS and OS were 86.2% (95% CI: 74.4%–99.8%) and 96.4% (95% CI: 89.8%–100%) respectively (Figure). Overall, 41% pts experienced grade (gr) 3/4 treatment-related adverse events (TrAE) and 2 (6%) pts stopped therapy due to TrAEs (both nivolumab only). Treatment-related febrile neutropenia occurred in 5% of pts. Endocrine immune-mediated AEs (irAEs) were all Gr 1/2; nonendocrine irAEs included Gr 3 hepatitis (n = 1), Gr 2 colitis (n = 1), Gr 2 pneumonitis (n = 1) and Gr 1/2 rash (n = 7). GA data are currently being analyzed and will be reported at the meeting. The research was funded by: Bristol Myers Squibb Keywords: combination therapies, Hodgkin lymphoma, immunotherapy Conflicts of interests pertinent to the abstract P. Torka Consultant or advisory role: Genentech, GenMab, Lilly USA, Seagen Z. Epstein-Peterson Honoraria: OncLive Research funding: Kymera, Amgen, Viracta A. Kumar Consultant or advisory role: Genentech Honoraria: Astra Zeneca, Kite Pharmaceuticals, Janssen, Genentech, and Loxo/Lily Pharmaceuticals Research funding: AbbVie, Adaptive Biotechnologies, Celgene, Pharmacyclics, Loxo/Lily Pharmaceuticals, and Seattle Genetics S. Horwitz Consultant or advisory role: Affimed, Daiichi Sankyo, Kyowa Hakko Kirin, ONO Pharmaceuticals, SecuraBio, Shoreline Biosciences, Inc. Takeda, Yingli Pharma Limited, Abcuro, Inc. and Tubulis. Research funding: ADC Therapeutics, Affimed, Auxilius Pharma, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Millennium/Takeda, Seattle Genetics, C4, and Verastem/SecuraBio L. Falchi Consultant or advisory role: Roche, genentech, abbvie, Genmab, ADC therapeutics, seagen, astrazeneca Research funding: Roche, genentech, abbvie, Genmab Educational grants: Genmab W. Johnson Consultant or advisory role: Myeloid Therapeutics M. Palomba Consultant or advisory role: Synthekine, Cellectar, Beigene, Kite, BMS G. Salles Consultant or advisory role: Abbvie, Beigene, BMS/Celgene, Epizyme, Genentech/Roche, Genmab, Incyte, Janssen, Kite/Gilead, Loxo, Milteniy, Molecular Partners, Morphosys, Nordic Nanovector, Novartis, Rapt, Takeda; Debiopharm/Velosbio/Ipsen Stock ownership: Owkin Honoraria: Abbvie, Bayer, Incyte, Kite/Gilead, Morphosys, Novartis, Regeneron A. Dogan Consultant or advisory role: Incyte, EUSA Pharma, Loxo Research funding: Roche and Takeda A. Zelenetz Employment or leadership position: Beigene- DMC Chair, BMS/Celgene/Juno—DMC Member Consultant or advisory role: Genentech/Roche Gilead, Celgene, Janssen, Amgen, Novartis, Adaptive Biotechnology, MorphoSys, Abbvie, AstraZeneca, MEI Pharma Research funding: MEI Pharmaceuticals, Genentech/Roche, Beigene, SPORE -PI (receives salary support and funds awarded to MSK) A. Moskowitz Honoraria: Seagen, Affimed, Bio Ascend, Imbrium Therapeutics L.P./Purdue, Janpix Ltd., Merck, Seattle Genetics, Tessa Therapeutics and Takeda Research funding: ADC Therapeutics, Beigene, Miragen, Seattle Genetics, Merck, Bristol-Myers Squibb, Incyte, and SecuraBio