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.