PURPOSE: 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. METHODS: 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. RESULTS: 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 (P = .041). CONCLUSION: Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

Barbara Ann Karmanos Cancer Institute Detroit MI

Brigham and Women's Hospital Boston MA

Bristol Myers Squibb Princeton NJ

British Columbia Cancer Centre for Lymphoid Cancer Vancouver British Columbia Canada

Charles University Prague and General University Hospital Prague Prague Czech Republic

Costa del Sol Hospital Marbella Spain and Institute of Biomedical Research in Málaga Málaga Spain

Dana Farber Cancer Institute Boston MA

Hospital Duran i Reynals Barcelona Spain

Hospital Universitario Puerta de Hierro Madrid Spain

Innsbruck University Hospital Innsbruck Austria

John Theurer Cancer Center at Hackensack Meridian Health Hackensack NJ

Mayo Clinic Rochester MN

Medical University of Vienna Vienna Austria

OncoTyrol Center of Personalized Cancer Medicine Innsbruck Austria

University of Tennessee Knoxville TN

University of Texas MD Anderson Cancer Center Houston TX

Winship Cancer Institute Emory University Atlanta GA

Nat Rev Clin Oncol. 2019 Oct;16(10):599-600. doi: 10.1038/s41571-019-0255-8. PubMed

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Toxicity of Immune-Checkpoint Inhibitors in Hematological Malignancies

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