Positron Emission Tomography–Guided Brentuximab Vedotin, Etoposide, Cyclophosphamide, Doxorubicin, Dacarbazine, and Dexamethasone in Older Patients With Advanced-Stage Classic Hodgkin Lymphoma: A Prospective, Multicenter, Single-Arm, Phase II Cohort of the German Hodgkin Study Group HD21 Trial
Abstract
PURPOSE Positron emission tomography (PET)-guided therapy with 4-6 cycles of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD) is highly effective in younger patients with advanced-stage classic Hodgkin lymphoma (AS-cHL). We report feasibility and efficacy of PET-guided BrECADD as first-line treatment in older patients with AS-cHL. PATIENTS AND METHODS Patients with AS-cHL aged 61-75 years were enrolled in a phase II single-arm cohort of the HD21 trial (ClinicalTrials.gov identifier: NCT02661503 ). Patients with negative PET/computed tomography after 2×BrECADD (PET2) received a total of 4×BrECADD, while PET2-positive patients received 6×BrECADD. The primary end point was the centrally reviewed complete remission (CR) rate after the end of chemotherapy (EOC). Secondary end points included feasibility, adverse events, treatment-related morbidity (TRMB), progression-free survival (PFS), overall survival (OS), and health-related quality of life (HRQoL). RESULTS Between June 2020 and April 2023, 85 patients were enrolled, of whom 83 with a median age of 67 years (range, 61-75) were analyzed in the intention-to-treat cohort. Most prevalent ≥grade 3 toxicities included leukopenia (n = 80 [96%]), thrombocytopenia (n = 71 [86%]), anemia (n = 57 [69%]), and febrile neutropenia (n = 46 [55%]). Forty-eight (60%) of 80 patients with centrally reviewed PET2 were scheduled for 4×BrECADD and 32 (40%) for 6×BrECADD. Of these, 71 patients (89%) received the target number of cycles. Sixty-eight patients (82%; 95% CI, 72 to 90) achieved CR at EOC. PFS and OS estimates at 2 years were 91.5% (95% CI, 85 to 98) and 90.8% (95% CI, 84 to 98), respectively. No death was attributed to study treatment. Initially, impaired HRQoL scores improved during follow up and on average reached population reference values. CONCLUSION PET-guided BrECADD in older patients is feasible and effective. With a PFS rate on par with that of younger patients, short duration, and limited anthracycline exposure, BrECADD is a valuable treatment option also for older patients with AS-cHL.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (35)
Justin Ferdinandus
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Helen Kaul
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Alexander Fosså
Andreas Hüttmann
Felix Keil
11Hanusch Krankenhaus, Vienna, Austria
Yon-Dschun Ko
Felicitas Hitz
7Oncology Kantonsspital St.Gallen, Department of Internal Medicine, St. Gallen, Switzerland
Michaela Schwarz
Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Virchow Clinic, Berlin, Germany
Corinna Trenker
Department of Internal Medicine, Hematology, Oncology and Immunology, Philipps University Marburg and University Hospital Giessen and Marburg, Campus Marburg, Marburg, Germany
Andrea Kerkhoff
7Medizinische Klinik A, University Hospital Münster, Münster, Germany
Peter Staib
4Department of Haematology and Oncology, St. Antonius Krankenhaus Eschweiler, Eschweiler, Germany
Kai Wille
University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care, Johannes Wesling Medical Center Minden, University of Bochum, Bochum, Germany
Irmgard Dresel
Ortenau Klinikum, Offenburg, Germany
Dennis Hahn
Department of Hematology, Oncology, Stem-Cell Transplantation, and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany
Bernd Hertenstein
17Department of Hematology and Oncology, Klinikum Bremen-Mitte, Bremen, Germany
Peter Moosmann
Cantonal Hospital Aarau, Aarau, Switzerland
Ulrich Mey
17Kantonsspital Graubuenden, Oncology and Hematology, for the Swiss Group for Clinical Cancer Research (SAKK), Chur, Switzerland
Stefan Balabanov
Department of Medical Oncology and Hematology, University Hospital of Zurich, Zurich, Switzerland
Tasman Armytage
Department of Haematology Gosford Hospital, Gosford, Australia
Fernando Roncolato
Johannes C. Hellmuth
8Department of Medicine III, Ludwig Maximilian University Hospital Munich, Munich, Germany
Mark Hertzberg
Carsten Kobe
11Department of Nuclear Medicine and German Hodgkin Study Group, University Hospital of Cologne, Cologne, Germany
Wolfram Klapper
Christian Baues
12Department of Radiation Oncology and German Hodgkin Study Group, Hospital Bochum, Bochum, Germany
Hans-Theodor Eich
Department of Radiotherapy, University Hospital of Muenster, Muenster, Germany
Stefanie Kreissl
Ordensklinikum Linz Elisabethinen, Linz, Austria
Michael Fuchs
Janina Jablonski
2German Hodgkin Study Group and University Hospital Cologne, Cologne, Germany
Gundolf Schneider
1Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Medical Faculty and University Hospital Cologne, Cologne, Germany
Hishan Tharmaseelan
1University of Cologne, Faculty of Medicine and University Hospital of Cologne, Department I of Internal Medicine, and Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), and German Hodgkin Study Group (GHSG), Cologne, Germany
Dennis A. Eichenauer
29Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, University of Cologne, Cologne, Germany
Bastian von Tresckow
1Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Department I of Internal Medicine, Faculty of Medicine and University Hospital of Cologne, University of Cologne, and German Hodgkin Study Group, Cologne, Germany
Peter Borchmann
Uniklinik Koeln, Koeln, Germany
Paul J. Bröckelmann