PET‐Adapted Therapy with Nivolumab plus Adriamycin, Vinblastine, and Dacarbazine for Newly Diagnosed Stage III or IV Hodgkin Lymphoma

Introduction: Interim PET is highly predictive of outcome for patients (pts) with stage III or IV Hodgkin lymphoma (HL) treated with 6 cycles of Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). The RATHL study showed that PET-2 negative (neg) pts receiving 6 cycles of ABVD can stop bleomycin after 2 cycles without compromising efficacy. Furthermore, PET-2 positive (pos) pts appear to have improved outcomes if treatment is intensified with BEACOPP (Johnson, et al. NEJM 2016). We hypothesized that introduction of programmed death (PD)-1 blockade may also improve outcomes for PET-2 pos pts and allow them to avoid BEACOPP-associated toxicity. Methods: We conducted a multicenter, investigator-initiated phase II study for pts with newly diagnosed stage III or IV HL. Pts initially received 2 cycles of ABVD. PET-2 neg pts (defined as Deauville score of 3 or better) received 4 additional cycles of AVD. PET-2 pos pts received 4 cycles of AVD plus nivolumab (240 mg IV every 14 days). Pts could receive cycles 1 and 2 of ABVD off-study and enroll if PET-2 was determined to be positive (Deauville score 4 or 5). The primary endpoint was 2-year progression-free survival (PFS) for PET-2 pos pts. The study was initially designed to enroll 26 PET-2 pos pts however due to slow accrual, the study was closed after 19 PET-2 pos pts enrolled. Results: 39 pts enrolled, including 20 PET-2 neg and 19 PET-2 pos. 26 pts received cycles 1 and 2 of ABVD on-study. Among them, 20 (77%) were PET-2 neg and 6 (23%) PET-2 pos. An additional 13 pts received cycles 1 and 2 of ABVD off-study and enrolled based upon PET-2 positivity. Among the 39 pts, median age was 35 years (19–58), 74% had stage IV disease, and 46% had IPS score of 3–7 (Table). Among PET-2 neg pts there were 3 events; 1 pt with biopsy confirmed refractory HL and 2 with biopsy-confirmed relapse of HL 6 and 23 months after treatment completion. Among PET-2 pos pts there were 6 events; 2 pts remained PET-positive on PET-6 and end of treatment biopsies showed gray zone lymphoma and T-cell/histiocyte rich B cell lymphoma, respectively. 4 PET-2 pos pts developed biopsy-confirmed relapse of HL 7–18 months after treatment completion. 2-yr PFS (Figure) for PET-2 neg and pos pts were 90% (95% CI: 78–100) and 65.7% (95% CI: 46.6–92.6), respectively. After a median follow-up of 36 months, there was 1 death (in a PET-2 neg pt who experienced sudden death while in remission 3 years after treatment completion). The research was funded by: Bristol Myers Squibb; Adam R. Spector Foundation Keywords: Chemotherapy, Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract. A. Moskowitz Honoraria: Affimed, Imbrium Therapeutics L.P./Purdue, Janpix Ltd., Merck, Seattle Genetics, and Takeda Research funding: ADC Therapeutics, Beigene, Miragen, Seattle Genetics, Merck, Bristol-Myers Squibb, Incyte, and SecuraBio Z. Epstein-Peterson Research funding: Kymera, Amgen, Viracta A. Kumar Consultant or advisory role: Genentech Honoraria: stra Zeneca, Kite Pharmaceuticals, Janssen, Genentech, and Loxo/Lily Pharmaceuticals Research funding: AbbVie, Adaptive Biotechnologies, Celgene, Pharmacyclics, Loxo/Lily Pharmaceuticals, and Seattle Genetics A. Zelenetz 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 Other remuneration: Beigene – DMC Chair, BMS/Celgene/Juno – DMC Member 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. L. 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 P. Torka Consultant or advisory role: Genentech, GenMab, Seagen and Lilly USA A. Dogan Consultant or advisory role: Incyte, EUSA Pharma, Loxo Research funding: Roche and Takeda.