B-CAP (brentuximab vedotin, cyclophosphamide, doxorubicin and predniso(lo)Ne) in Older Patients with Advanced-Stage Hodgkin Lymphoma: Results of a Phase II Intergroup Trial By the German Hodgkin Study Group (GHSG) and the Nordic Lymphoma Group (NLG) (2018)

Abstract 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% CI 90.5%-100%) with 21 patients having CR, 26 patients having PR, and one patient having progressive disease in the restaging after completion of B-CAP therapy. All patients with CT-based CR and 10/26 patients with PR had a negative PET (Deauville &lt; 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. Disclosures Boell: honoraria and research funding from Celgene, MSD, Mundipharma, Johnson &amp; Johnson and Takeda: Consultancy, Honoraria, Research Funding. Fosså:Janssen Pharmaceuticals, Inc.: Honoraria. Leppa:Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy; Bayer: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Molin:Bristol-Myers Squibb: Honoraria; Roche Holding AG: Honoraria; Merck &amp; Co., Inc: Honoraria; Takeda Pharmaceuticals: Research Funding. Borchmann:Novartis: Consultancy, Honoraria.