Alexander Fosså1, Boris Böll2, Helen Goergen2, Peter Kamper3, Sirpa Leppä4, Daniel Molin5, Julia Meissner6, Ellen Ritter7, Jacob Haaber8, Martin Hutchings9, Michael Fuchs2, Andreas Engert2, Carsten Kobe10, Peter Borchmann2, on behalf of the German Hodgkin Study Group and the Nordic Lymphoma Group
1 Department of Oncology, Oslo University Hospital, Oslo, Norway, 2 Department I of Internal Medicine, German Hodgkin Study Group, University Hospital of Cologne, Cologne, Germany, 3 Department of Hematology, Aarhus University Hospital, Aarhus, Denmark, 4 Helsinki University Hospital Cancer Centre and University of Helsinki, Department of Oncology, Helsinki, Finland, 5 Experimental and Clinical Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden, 6 Fifth Department of Internal Medicine, University Hospital of Heidelberg, Heidelberg, Germany, 7 Internal Medicine II, Hematology and Internal Oncology, Jena University Hospital, Jena, Germany, 8 Department of Hematology, Odense University Hospital, Odense, Denmark, 9 Department of Hematology, Rigshospitalet, Copenhagen, Denmark, 10 Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany
Background: About 20% of patients diagnosed with classical Hodgkin lymphoma (cHL) are 60 years or older. They have a comparatively poor prognosis, particularly when presenting in advanced stages. In previous trials, older patients did not benefit from intensified regimens in terms of overall survival due to a high toxicity-related death rate. In order to improve tolerability, we developed the B-CAP regimen (brentuximab vedotin, cyclophosphamide, doxorubicin and predniso(lo)ne), incorporating the antibody-drug conjugate brentuximab vedotin into a CHOP-based chemotherapy backbone. We report the first results of our multicenter phase II study evaluating B-CAP in older cHL patients.
Methods: We recruited patients with newly diagnosed advanced-stage cHL aged 60 years or older and eligible for polychemotherapy (Cumulative Illness Rating Scale for Geriatrics ≤6 in total and ≤3 per organ system) in five European countries. Treatment consisted of six cycles B-CAP; radiotherapy to Positron Emission Tomography (PET) positive residuals was applied. The primary endpoint was the CT-based objective response rate (ORR; complete [CR] or partial remission [PR]) after six cycles of B-CAP, aiming at excluding an ORR of 60% or less via a one-sided 95% confidence interval. All patients completing interim staging after two cycles were considered eligible.
Results: Between November 2015 and September 2017, 50 patients were recruited, of whom one withdrew consent before start of treatment. Of the remaining 49, 26 patients (53%) were male, 47 (96%) had stage III-IV disease, and the median age was 66 years (range 60–84). One patient died from infection before interim staging, and 48 patients were eligible for the primary endpoint. There were no further treatment-related deaths. The CT-based ORR was 98% (one-sided 95% confidence interval 91%–100%) with 21 patients having CR, 26 patients having PR, and one patient having progressive disease in restaging after completion of B-CAP therapy. All patients with CT-based CR and 10/26 patients with PR had a negative PET (Deauville < 4), resulting in a complete metabolic response rate of 65%. Dose delivery was high with only two patients stopping treatment after four and five cycles, respectively, due to toxicity. Progression-free and overall survival as well as safety data will be presented.
Conclusion: B-CAP is feasible and effective in patients older than 60 years with advanced-stage cHL and should be subject of further research.