Format

Send to

Choose Destination
J Clin Oncol. 2019 Dec 1;37(34):3291-3299. doi: 10.1200/JCO.19.01389. Epub 2019 Oct 14.

Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma.

Author information

1
Dana-Farber Cancer Institute, Boston, MA.
2
Pirogov National Medical Surgical Center, Moscow, Russia.
3
Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France.
4
Hôpital Haut-Levêque, Pessac, France.
5
N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
6
Ankara University Medical School, Ankara, Turkey.
7
Clinica Alemana de Santiago, Santiago, Chile.
8
Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil.
9
Hospital Clínico de Salamanca, Salamanca, Spain.
10
Maria Sklodowska-Curie Institute Oncology Center, Warszawa, Poland.
11
Anadolu Medical Center, Gebze, Turkey.
12
Institut Gustave Roussy, Paris, France.
13
The Ohio State University Comprehensive Cancer Center, Columbus, OH.
14
Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
15
Universite Claude Bernard Lyon, Lyon, France.
16
University of Pennsylvania, Philadelphia, PA.
17
City of Hope, Duarte, CA.
18
Brigham & Women's Hospital, Boston, MA.
19
Merck & Co, Kenilworth, NJ.
20
Institute of Hematology, Seràgnoli University of Bologna, Bologna, Italy.

Abstract

PURPOSE:

Patients with relapsed or refractory primary mediastinal large B-cell lymphoma (rrPMBCL) have a poor prognosis, and their treatment represents an urgent and unmet need. Because PMBCL is associated with genetic aberrations at 9p24 and overexpression of programmed cell death-1 (PD-1) ligands (PD-L1), it is hypothesized to be susceptible to PD-1 blockade.

METHODS:

In the phase IB KEYNOTE-013 (ClinicalTrials.gov identifier: NCT01953692) and phase II KEYNOTE-170 (ClinicalTrials.gov identifier: NCT02576990) studies, adults with rrPMBCL received pembrolizumab for up to 2 years or until disease progression or unacceptable toxicity. The primary end points were safety and objective response rate in KEYNOTE-013 and objective response rate in KEYNOTE-170. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Exploratory end points included association between biomarkers and pembrolizumab activity.

RESULTS:

The objective response rate was 48% (7 complete responses; 33%) among 21 patients in KEYNOTE-013 and 45% (7 complete responses; 13%) among 53 patients in KEYNOTE-170. After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study. No patient with complete response experienced progression, including 2 patients with complete response for at least 1 year off therapy. Treatment-related adverse events occurred in 24% of patients in KEYNOTE-013 and 23% of patients in KEYNOTE-170. There were no treatment-related deaths. Among 42 evaluable patients, the magnitude of the 9p24 gene abnormality was associated with PD-L1 expression, which was itself significantly associated with progression-free survival.

CONCLUSION:

Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with rrPMBCL.

PMID:
31609651
PMCID:
PMC6881098
[Available on 2020-12-01]
DOI:
10.1200/JCO.19.01389

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center