Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study

• Published in: Journal of clinical oncology Vol. 37; no. 23; pp. 1997 - 2007
• Main Authors: Ramchandren, Radhakrishnan, Domingo-Domènech, Eva, Rueda, Antonio, Trněný, Marek, Feldman, Tatyana A., Lee, Hun Ju, Provencio, Mariano, Sillaber, Christian, Cohen, Jonathon B., Savage, Kerry J., Willenbacher, Wolfgang, Ligon, Azra H., Ouyang, Jing, Redd, Robert, Rodig, Scott J., Shipp, Margaret A., Sacchi, Mariana, Sumbul, Anne, Armand, Philippe, Ansell, Stephen M.
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.08.2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Cohort Studies; Female; Hodgkin Disease - drug therapy; Humans; Male; Middle Aged; Neoplasm Staging - methods; Nivolumab - pharmacology; Nivolumab - therapeutic use; RAPID COMMUNICATION; Young Adult
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.19.00315

Nivolumab, an anti-programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( = .041). Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.