Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma: Safety and efficacy in the phase II CheckMate 205 study

Radhakrishnan Ramchandren, Eva Domingo-Domènech, Antonio Rueda, Marek Trněný, Tatyana A. Feldman, Hun Ju Lee, Mariano Provencio, Christian Sillaber, Jonathon B. Cohen, Kerry J. Savage, Wolfgang Willenbacher, Azra H. Ligon, Jing Ouyang, Robert Redd, Scott J. Rodig, Margaret A. Shipp, Mariana Sacchi, Anne Sumbul, Philippe Armand, Stephen Maxted Ansell

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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.

Original languageEnglish (US)
Pages (from-to)1997-2007
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number23
DOIs
StatePublished - Aug 10 2019

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Hodgkin Disease
Safety
Disease-Free Survival
Reed-Sternberg Cells
Ligands
Febrile Neutropenia
Dacarbazine
Vinblastine
nivolumab
Advisory Committees
Therapeutics
Exanthema
Radiology
Doxorubicin
Disease Progression
Adrenal Cortex Hormones
Chromosomes
Monoclonal Antibodies
Recurrence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma : Safety and efficacy in the phase II CheckMate 205 study. / 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 Maxted.

In: Journal of Clinical Oncology, Vol. 37, No. 23, 10.08.2019, p. 1997-2007.

Research output: Contribution to journalArticle

Ramchandren, R, Domingo-Domènech, E, Rueda, A, Trněný, M, Feldman, TA, Lee, HJ, Provencio, M, Sillaber, C, Cohen, JB, Savage, KJ, Willenbacher, W, Ligon, AH, Ouyang, J, Redd, R, Rodig, SJ, Shipp, MA, Sacchi, M, Sumbul, A, Armand, P & Ansell, SM 2019, 'Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma: Safety and efficacy in the phase II CheckMate 205 study', Journal of Clinical Oncology, vol. 37, no. 23, pp. 1997-2007. https://doi.org/10.1200/JCO.19.00315
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 Maxted. / Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma : Safety and efficacy in the phase II CheckMate 205 study. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 23. pp. 1997-2007.
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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.",
author = "Radhakrishnan Ramchandren and Eva Domingo-Dom{\`e}nech and Antonio Rueda and Marek Trněn{\'y} and Feldman, {Tatyana A.} and Lee, {Hun Ju} and Mariano Provencio and Christian Sillaber and Cohen, {Jonathon B.} and Savage, {Kerry J.} and Wolfgang Willenbacher and Ligon, {Azra H.} and Jing Ouyang and Robert Redd and Rodig, {Scott J.} and Shipp, {Margaret A.} and Mariana Sacchi and Anne Sumbul and Philippe Armand and Ansell, {Stephen Maxted}",
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TY - JOUR

T1 - Nivolumab for newly diagnosed advanced-stage classic Hodgkin lymphoma

T2 - Safety and efficacy in the phase II CheckMate 205 study

AU - Ramchandren, Radhakrishnan

AU - Domingo-Domènech, Eva

AU - Rueda, Antonio

AU - Trněný, Marek

AU - Feldman, Tatyana A.

AU - Lee, Hun Ju

AU - Provencio, Mariano

AU - Sillaber, Christian

AU - Cohen, Jonathon B.

AU - Savage, Kerry J.

AU - Willenbacher, Wolfgang

AU - Ligon, Azra H.

AU - Ouyang, Jing

AU - Redd, Robert

AU - Rodig, Scott J.

AU - Shipp, Margaret A.

AU - Sacchi, Mariana

AU - Sumbul, Anne

AU - Armand, Philippe

AU - Ansell, Stephen Maxted

PY - 2019/8/10

Y1 - 2019/8/10

N2 - 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.

AB - 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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