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Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial.
Al-Sawaf, Othman; Ligtvoet, Rudy; Robrecht, Sandra; Stumpf, Janina; Fink, Anna-Maria; Tausch, Eugen; Schneider, Christof; Boettcher, Sebastian; Mikusko, Martin; Ritgen, Matthias; Schetelig, Johannes; von Tresckow, Julia; Vehling-Kaiser, Ursula; Gaska, Tobias; Wendtner, Clemens Martin; Chapuy, Bjoern; Fischer, Kirsten; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Staber, Philipp; Niemann, Carsten; Hallek, Michael; Eichhorst, Barbara.
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  • Al-Sawaf O; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany. othman.al-sawaf@uk-koeln.de.
  • Ligtvoet R; Francis Crick Institute London, London, UK. othman.al-sawaf@uk-koeln.de.
  • Robrecht S; Cancer Institute, University College London, London, UK. othman.al-sawaf@uk-koeln.de.
  • Stumpf J; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Fink AM; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Tausch E; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Schneider C; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Boettcher S; Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.
  • Mikusko M; Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.
  • Ritgen M; Department III of Internal Medicine, University Hospital Rostock, Rostock, Germany.
  • Schetelig J; Department of Haematology and Oncology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
  • von Tresckow J; Department II of Internal Medicine, Campus Kiel, University of Schleswig-Holstein, Kiel, Germany.
  • Vehling-Kaiser U; Department I of Internal Medicine, University Hospital Carl Gustav Carus, Dresden, Germany.
  • Gaska T; Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Wendtner CM; MVZ Dr Vehling-Kaiser, Landshut, Germany.
  • Chapuy B; Department of Hematology and Oncology, Brüderkrankenhaus St. Josef, Paderborn, Germany.
  • Fischer K; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
  • Kreuzer KA; Department of Hematology and Medical Oncology, Georg-August University Göttingen, Göttingen, Germany.
  • Stilgenbauer S; Department of Hematology, Oncology, and Cancer Immunology, Charité -University Medical Center Berlin, Campus Benjamin Franklin, Berlin, Germany.
  • Staber P; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Niemann C; Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.
  • Hallek M; Department III of Internal Medicine, University Hospital Ulm, Ulm, Germany.
  • Eichhorst B; Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
Nat Med ; 30(1): 240-248, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38071379
In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45-82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2-72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study's primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8-16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4-91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956 .
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperidinas / Pirazoles / Pirimidinas / Leucemia Linfocítica Crónica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Anticuerpos Monoclonales Humanizados Límite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperidinas / Pirazoles / Pirimidinas / Leucemia Linfocítica Crónica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Anticuerpos Monoclonales Humanizados Límite: Aged / Aged80 / Humans / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos