PMID- 27354476
OWN - NLM
STAT- MEDLINE
DCOM- 20171227
LR  - 20240327
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 34
IP  - 31
DP  - 2016 Nov 1
TI  - Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin 
      Lymphoma After Brentuximab Vedotin Failure.
PG  - 3733-3739
LID - 10.1200/JCO.2016.67.3467 [doi]
AB  - Purpose Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations 
      leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a 
      possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 
      (NCT01953692) tested the safety and efficacy of the anti-PD-1 antibody 
      pembrolizumab in patients with hematologic malignancies. Based on its genetics, 
      HL was included as an independent cohort. Methods We enrolled patients with 
      relapsed or refractory HL whose disease progressed on or after treatment with 
      brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, 
      until disease progression occurred. Response to treatment was assessed at week 12 
      and every 8 weeks thereafter. Principal end points were safety and complete 
      remission (CR) rate. Results Thirty-one patients were enrolled; 55% had more than 
      four lines of prior therapy, and 71% had relapsed after autologous stem cell 
      transplantation. Five patients (16%) experienced grade 3 drug-related adverse 
      events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR 
      rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial 
      remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the 
      responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a 
      median follow-up of 17 months. The progression-free survival rate was 69% at 24 
      weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of 
      PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural 
      killer cells, and activation of interferon-gamma, T-cell receptor, and expanded 
      immune-related signaling pathways. Conclusions Pembrolizumab was associated with 
      a favorable safety profile. Pembrolizumab treatment induced favorable responses 
      in a heavily pretreated patient cohort, justifying further studies.
FAU - Armand, Philippe
AU  - Armand P
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Shipp, Margaret A
AU  - Shipp MA
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Ribrag, Vincent
AU  - Ribrag V
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Michot, Jean-Marie
AU  - Michot JM
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Zinzani, Pier Luigi
AU  - Zinzani PL
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Kuruvilla, John
AU  - Kuruvilla J
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Snyder, Ellen S
AU  - Snyder ES
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Ricart, Alejandro D
AU  - Ricart AD
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Balakumaran, Arun
AU  - Balakumaran A
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Rose, Shelonitda
AU  - Rose S
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
FAU - Moskowitz, Craig H
AU  - Moskowitz CH
AD  - Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; 
      Vincent Ribrag and Jean-Marie Michot, Institut Gustave Roussy, Villejuif, France; 
      Pier Luigi Zinzani, Institute of Hematology Seragnoli, University of Bologna, 
      Bologna, Italy; John Kuruvilla, Princess Margaret Cancer Centre and University of 
      Toronto, Toronto, Ontario, Canada; Ellen S. Snyder, Alejandro D. Ricart, Arun 
      Balakumaran, and Shelonitda Rose, Merck, Kenilworth, NJ; and Craig H. Moskowitz, 
      Memorial Sloan Kettering Cancer Center, New York, NY.
LA  - eng
SI  - ClinicalTrials.gov/NCT01953692
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA161026/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Immunoconjugates)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 7XL5ISS668 (Brentuximab Vedotin)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
CIN - Nat Rev Clin Oncol. 2016 Jul 20;13(8):466. PMID: 27435267
CIN - Int J Radiat Oncol Biol Phys. 2018 Dec 1;102(5):1396-1399. PMID: 31014778
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Antineoplastic Agents, Immunological/adverse effects/therapeutic use
MH  - B7-H1 Antigen/metabolism
MH  - Brentuximab Vedotin
MH  - Cohort Studies
MH  - Disease-Free Survival
MH  - Female
MH  - Hodgkin Disease/*drug therapy/metabolism
MH  - Humans
MH  - Immunoconjugates/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Programmed Cell Death 1 Receptor/*antagonists & inhibitors/metabolism
MH  - Remission Induction
MH  - Treatment Failure
MH  - Young Adult
PMC - PMC5791838
COIS- Authors' disclosures of potential conflicts of interest are found in the article 
      online at www.jco.org. Author contributions are found at the end of this article.
EDAT- 2016/06/30 06:00
MHDA- 2017/12/28 06:00
PMCR- 2016/06/27
CRDT- 2016/06/30 06:00
PHST- 2016/06/30 06:00 [pubmed]
PHST- 2017/12/28 06:00 [medline]
PHST- 2016/06/30 06:00 [entrez]
PHST- 2016/06/27 00:00 [pmc-release]
AID - JCO.2016.67.3467 [pii]
AID - 673467 [pii]
AID - 10.1200/JCO.2016.67.3467 [doi]
PST - ppublish
SO  - J Clin Oncol. 2016 Nov 1;34(31):3733-3739. doi: 10.1200/JCO.2016.67.3467.