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 M.
N1 - Funding Information:
Supported by Bristol-Myers Squibb, which also funded medical writing support. Also supported by the Center for Immuno-Oncology of the Dana-Farber Cancer Institute (S.J.R.), National Cancer Institute Grant No. R01 CA161026 (M.A.S.), and the Miller Family Fund (M.A.S.).
Publisher Copyright:
© 2019 by American Society of Clinical Oncolog.
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.
UR - http://www.scopus.com/inward/record.url?scp=85067302377&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067302377&partnerID=8YFLogxK
U2 - 10.1200/JCO.19.00315
DO - 10.1200/JCO.19.00315
M3 - Article
C2 - 31112476
AN - SCOPUS:85067302377
SN - 0732-183X
VL - 37
SP - 1997
EP - 2007
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -