Format

Send to

Choose Destination
J Clin Oncol. 2019 Aug 9:JCO1901492. doi: 10.1200/JCO.19.01492. [Epub ahead of print]

Nivolumab Combined With Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Efficacy and Safety From the Phase II CheckMate 436 Study.

Author information

1
Institute of Hematology "Seràgnoli" Bologna University, Bologna, Italy.
2
IRCCS Humanitas Research Hospital, Humanitas University, Milan, Italy.
3
Ospedale Papa Giovanni XXIII, Bergamo, Italy.
4
Hôpital Saint-Louis, Paris, France.
5
University of Rochester, Rochester, NY.
6
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
7
Royal Marsden Hospital, London, United Kingdom.
8
University of Chicago, Chicago, IL.
9
Jewish General Hospital, Montreal, Québec, Canada.
10
Washington University in St. Louis, St. Louis, MO.
11
Seattle Genetics, Bothell, WA.
12
Bristol-Myers Squibb, Princeton, NJ.
13
Memorial Sloan Kettering Cancer Center, New York, NY.

Abstract

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.

PMID:
31398081
DOI:
10.1200/JCO.19.01492

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center