TY - JOUR
T1 - Nivolumab combined with brentuximab vedotin for relapsed/refractory primary mediastinal large B-cell lymphoma
T2 - Efficacy and safety from the phase II checkmate 436 study
AU - Zinzani, Pier Luigi
AU - Santoro, Armando
AU - Gritti, Giuseppe
AU - Brice, Pauline
AU - Barr, Paul M.
AU - Kuruvilla, John
AU - Cunningham, David
AU - Kline, Justin
AU - Johnson, Nathalie A.
AU - Mehta-Shah, Neha
AU - Manley, Thomas
AU - Francis, Stephen
AU - Sharma, Manish
AU - Moskowitz, Alison J.
N1 - Funding Information:
Supported by Bristol-Myers Squibb, in collaboration with Seattle Genetics. Direct funding was provided by Bristol-Myers Squibb through the joint financial support of Bristol-Myers Squibb and Seattle Genetics.
Publisher Copyright:
© 2019 by American Society of Clinical Oncology
PY - 2019
Y1 - 2019
N2 - PURPOSE Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive non-Hodgkin lymphoma with poor outcomes in patients with relapsed/refractory (R/R) disease. PMBL is characterized by high expression of programmed death-1 ligand and variable expression of CD30. Nivolumab, an anti–programmed death-1 immune checkpoint inhibitor, and brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate, may have synergistic activity in R/R PMBL. METHODS The expansion cohort of the open-label, phase I/II CheckMate 436 study enrolled patients with confirmed R/R PMBL who were previously treated with either autologous hematopoietic cell transplantation or two or more prior chemotherapy regimens if ineligible for autologous hematopoietic cell transplantation. Patients received nivolumab (240 mg intravenously) and BV (1.8 mg/kg intravenously) every 3 weeks until disease progression or unacceptable toxicity. Primary end points were investigator-assessed objective response rate (ORR) per the Lugano 2014 criteria and safety. RESULTS Thirty patients with PMBL were treated and evaluable. At a median follow-up of 11.1 months, ORR (95% CI) was 73% (54% to 88%), with a 37% complete remission rate per investigator, and ORR of 70% (51% to 85%), with a 43% complete metabolic response rate per independent review. Median duration of response, median progression-free survival, and median overall survival have not been reached. Eleven responders had consolidation with autologous (n = 5) or allogeneic (n = 6) transplantation. Treatment-related adverse events were reported in 25 patients (83%). Sixteen patients (53%) had grade 3 to 4 treatment-related adverse events; the most common were neutropenia (n = 9), thrombocytopenia (n = 3), and peripheral neuropathy (n = 3). There were no treatment-related deaths. CONCLUSION In patients with R/R PMBL, the combination of nivolumab plus BV represents a promising option, with high antitumor activity and a manageable safety profile.
AB - PURPOSE Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive non-Hodgkin lymphoma with poor outcomes in patients with relapsed/refractory (R/R) disease. PMBL is characterized by high expression of programmed death-1 ligand and variable expression of CD30. Nivolumab, an anti–programmed death-1 immune checkpoint inhibitor, and brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate, may have synergistic activity in R/R PMBL. METHODS The expansion cohort of the open-label, phase I/II CheckMate 436 study enrolled patients with confirmed R/R PMBL who were previously treated with either autologous hematopoietic cell transplantation or two or more prior chemotherapy regimens if ineligible for autologous hematopoietic cell transplantation. Patients received nivolumab (240 mg intravenously) and BV (1.8 mg/kg intravenously) every 3 weeks until disease progression or unacceptable toxicity. Primary end points were investigator-assessed objective response rate (ORR) per the Lugano 2014 criteria and safety. RESULTS Thirty patients with PMBL were treated and evaluable. At a median follow-up of 11.1 months, ORR (95% CI) was 73% (54% to 88%), with a 37% complete remission rate per investigator, and ORR of 70% (51% to 85%), with a 43% complete metabolic response rate per independent review. Median duration of response, median progression-free survival, and median overall survival have not been reached. Eleven responders had consolidation with autologous (n = 5) or allogeneic (n = 6) transplantation. Treatment-related adverse events were reported in 25 patients (83%). Sixteen patients (53%) had grade 3 to 4 treatment-related adverse events; the most common were neutropenia (n = 9), thrombocytopenia (n = 3), and peripheral neuropathy (n = 3). There were no treatment-related deaths. CONCLUSION In patients with R/R PMBL, the combination of nivolumab plus BV represents a promising option, with high antitumor activity and a manageable safety profile.
UR - http://www.scopus.com/inward/record.url?scp=85075090096&partnerID=8YFLogxK
U2 - 10.1200/JCO.19.01492
DO - 10.1200/JCO.19.01492
M3 - Article
C2 - 31398081
AN - SCOPUS:85075090096
SN - 0732-183X
VL - 37
SP - 3081
EP - 3089
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 33
ER -