Toxicities at one year follow‐up in patients with advanced stage classical Hodgkin Lymphoma: results from the randomized phase III HD21 trial by the German Hodgkin Study Group

Abstract

Introduction: The HD21 trial compares BrECADD with eBEACOPP for the first-line treatment of advanced stage classical Hodgkin Lymphoma (AS-cHL). We previously reported a superior acute tolerability profile for BrECADD. However, persisting treatment sequelae as peripheral neuropathy or gonadal dysfunction are a major concern for survivors of AS-cHL. Accordingly, resolution of organ toxicities is highly relevant from the patient´s perspective. Therefore, we report treatment-related toxicities at twelve months follow-up (FU12) after treatment in HD21. Methods: Adult patients ≤60 years of age with AS-cHL were included in this ongoing international open label randomized phase III trial and randomized in a 1:1 ratio to receive PET2-guided 4–6 cycles of either standard eBEACOPP or experimental BrECADD treatment. For detection of treatment sequelae at FU12, non-hematological adverse events and serum levels of FSH levels are reported. The trial was registered at clinicaltrials.gov (NCT02661503) and conducted according to ICH-GCP guidelines. Results: Between July 2016 and August 2020, we enrolled 1,500 patients from 9 countries. Baseline characteristics were well balanced between treatment arms. Documented FU12 was available in 1395/1470 (94.9%) patients in the ITT cohort. 557 (80.8%) and 566 (80.2%) patients had no documented toxicity following eBEACOPP and BrECADD, respectively. At FU12, grade 2 or higher PNP was reported for 17 (2.7%) patients following eBEACOPP and for 12 (1.9%) patients following BrECADD; however, no or only grade 1 PNP was reported for most patients in both treatment groups with 97.3% for eBEACOPP and 98.1% for BrECADD. Rate of PNP was numerically higher in patients receiving 6 cycles of chemotherapy (3.0%) compared to 4 cycles (1.9%). FSH levels at FU12 were available for 597 patients and were higher for patients who received eBEACOPP (mean FSH 29.4 and 31.8 after 4 and 6 cycles, respectively) compared to BrECADD (mean FSH 18.3 and 20.5 after 4 and 6 cycles, respectively. Other than PNP, most frequent organ toxicities at FU12 were classified as respiratory, thoracic or mediastinal disorders (4.4%), and cardiac disorders (2.9%). All other organ toxicities were rare and equally distributed between trial arms. Conclusions: Complete resolution of acute adverse events is frequent following either regimen in the GHSG HD21 study. However, less patients report higher grade PNP or impaired gonadal function at FU12 after treatment with BrECADD than after eBEACOPP. Accordingly, persisting toxicities were reported in only few patients after BrECADD. Although these results are indicate good overall tolerability, they still need to be complemented by patient-reported outcomes for which analyses are ongoing. The non-inferiority of the experimental BrECADD regimen also remains to be demonstrated to draw definitive conclusions. The research was funded by: Takeda Keywords: Hodgkin lymphoma, Molecular Targeted Therapies, Ongoing Trials Conflicts of interests pertinent to the abstract. P. Borchmann Consultant or advisory role: Takeda Oncology, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Amgen, Miltenyi Biotech Honoraria: Takeda Oncology, Novartis, Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Miltenyi Biotech, Incyte, Abbvie Research funding: Takeda Oncology, Roche, Novartis, Merck Sharp & Dohme, Amgen