Radhakrishnan Ramchandren1,2, Eva Domingo-Domènech3, Antonio Rueda4, Marek Trněný5, Tatyana A Feldman6, Hun Ju Lee7, Mariano Provencio8, Christian Sillaber9, Jonathon B Cohen10, Kerry J Savage11, Wolfgang Willenbacher12,13, Azra H Ligon14, Jing Ouyang15, Robert Redd15, Scott J Rodig14,15, Margaret A Shipp15, Mariana Sacchi16, Anne Sumbul16, Philippe Armand15, Stephen M Ansell17. 1. 1University of Tennessee, Knoxville, TN. 2. 2Barbara Ann Karmanos Cancer Institute, Detroit, MI. 3. 3Hospital Duran i Reynals, Barcelona, Spain. 4. 4Costa del Sol Hospital, Marbella, Spain, and Institute of Biomedical Research in Málaga (IBIMA), Málaga, Spain. 5. 5Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. 6. 6John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ. 7. 7University of Texas MD Anderson Cancer Center, Houston, TX. 8. 8Hospital Universitario Puerta de Hierro, Madrid, Spain. 9. 9Medical University of Vienna, Vienna, Austria. 10. 10Winship Cancer Institute, Emory University, Atlanta, GA. 11. 11British Columbia Cancer Centre for Lymphoid Cancer, Vancouver, British Columbia, Canada. 12. 12Innsbruck University Hospital, Innsbruck, Austria. 13. 13OncoTyrol-Center of Personalized Cancer Medicine, Innsbruck, Austria. 14. 14Brigham and Women's Hospital, Boston, MA. 15. 15Dana-Farber Cancer Institute, Boston, MA. 16. 16Bristol-Myers Squibb, Princeton, NJ. 17. 17Mayo Clinic, Rochester, MN.
Abstract
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.
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.
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