Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma.
Robert W. Chen,Pier Luigi Zinzani,Michelle A. Fanale,Philippe Armand,Nathalie A. Johnson,Pauline Brice,John Radford,Vincent Ribrag,Daniel Molin,Theodoros P. Vassilakopoulos,Akihiro Tomita,Bastian von Tresckow,Margaret A. Shipp,Yinghua Zhang,Alejandro D. Ricart,Arun Balakumaran,Craig H. Moskowitz +16 more
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Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.Abstract:
Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.read more
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Regulation and Function of the PD-L1 Checkpoint
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Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial
Hussein Abdul-Hassan Tawbi,Melissa Amber Burgess,Vanessa Bolejack,Brian A. Van Tine,Scott M. Schuetze,James C. Hu,Sandra P. D'Angelo,Steven Attia,Richard F. Riedel,Dennis A. Priebat,Sujana Movva,Lara E. Davis,Scott H. Okuno,Damon R. Reed,John Crowley,Lisa H. Butterfield,Ruth Salazar,Jaime Rodriguez-Canales,Alexander J. Lazar,Ignacio I. Wistuba,Laurence H. Baker,Robert G. Maki,Denise K. Reinke,Shreyaskumar Patel +23 more
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Bruce D. Cheson,Beate Pfistner,Malik E. Juweid,Randy D. Gascoyne,Lena Specht,Sandra J. Horning,Bertrand Coiffier,Richard I. Fisher,Anton Hagenbeek,Emanuele Zucca,Steven T. Rosen,Sigrid Stroobants,T. Andrew Lister,Richard T. Hoppe,Martin Dreyling,Kensei Tobinai,Julie M. Vose,Joseph M. Connors,Massimo Federico,Volker Diehl +19 more
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Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma
Anas Younes,Ajay K. Gopal,Scott E. Smith,Stephen M. Ansell,Joseph D. Rosenblatt,Kerry J. Savage,Radhakrishnan Ramchandren,Nancy L. Bartlett,Bruce D. Cheson,Sven de Vos,Andres Forero-Torres,Craig H. Moskowitz,Joseph M. Connors,Andreas Engert,Emily K. Larsen,Dana A. Kennedy,Eric L. Sievers,Robert T. Chen +17 more
TL;DR: The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after autologous stem-cell transplantation (auto-SCT).
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Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial
Anas Younes,Armando Santoro,Margaret A. Shipp,Pier Luigi Zinzani,John M. Timmerman,Stephen M. Ansell,Philippe Armand,Michelle A. Fanale,Voravit Ratanatharathorn,John Kuruvilla,Jonathon B. Cohen,Graham P. Collins,Kerry J. Savage,Marek Trneny,Kazunobu Kato,Benedetto Farsaci,Susan M. Parker,Scott J. Rodig,Margaretha G.M. Roemer,Azra H. Ligon,Andreas Engert +20 more
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The biology of Hodgkin's lymphoma.
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Journal ArticleDOI
Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure
Philippe Armand,Margaret A. Shipp,Vincent Ribrag,Jean-Marie Michot,Pier Luigi Zinzani,John Kuruvilla,Ellen Snyder,Alejandro D. Ricart,Arun Balakumaran,Shelonitda Rose,Craig H. Moskowitz +10 more
TL;DR: Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.
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