Impact of Treatment-Related Morbidity on Health-Related Quality of Life in Patients with Advanced-Stage Classical Hodgkin Lymphoma Receiving Multiagent Therapy: Findings from the HD21 Study
Authors: Kristo Fjoralba , Mazerolle Flora , Alin Thibaud , Regnault Antoine , Ferdinandus Justin , Behringer Karolin , Jablonski Janina , Borchmann Peter , Ashaye Ajibade 
Published: December 2024

Introduction: The German Hodgkin Study Group (GHSG) HD21 randomized trial results showed that BrECADD had a more favorable toxicity profile and higher progression-free survival than eBEACOPP. The HD21 study co-primary endpoint demonstrated significantly reduced treatment-related morbidity (TRMB), with at least 1 TRMB reported in 42% and 59% of pts treated with BrECADD and eBEACOPP respectively. TRMB included severe acute hematological and nonhematological toxicities that can result in dose delay or reduction, and could negatively impact health-related quality of life (HRQoL). This post-hoc analysis explored the impact of TRMB on HRQoL.
Methods: The study randomized 1,500 pts (1:1) to receive BrECADD or eBEACOPP in 4-6, 21-day, treatment cycles. TRMB included any Common Terminology Criteria for Adverse Events (CTCAE) acute hematological (grade 4 anemia, thrombocytopenia, infections) and nonhematological (grade ≥3 cardiac, gastrointestinal, hepatobiliary, nervous system, renal/urinary, and respiratory, thoracic and mediastinal disorders) toxicity collected during the treatment period. The patient-reported European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 items (QLQ-C30) was administered at baseline, during the treatment period and posttreatment follow-up (FU) period up to 60 months (mth)s. Physical functioning (PF), fatigue (FA), and global health/quality of life (GH/QL) were identified as key concepts that could be negatively impacted by TRMB. PRO description according to TRMB and multivariate analysis of PROs according to TRMB, adjusted for age, sex and baseline PROs, were carried out at each available visit.
Results: The PRO analysis set (PAS - all pts with a baseline PRO and at least one postbaseline PRO from the intent-to-treat (ITT) population) included 732 pts (54% male, mean age of 34 years, and 68% with ECOG of 0 at baseline). Pts who had TRMB tended to report poorer overall health, PF, and more fatigue, with overall mean PRO scores lower (GH/QL and PF) or higher (FA) in pts with TRMB than in pts without TRMB. Mean GH/QL in pts with TRMB vs. those without TRMB was 51.2 vs. 57.8 at restaging after chemotherapy (RaC), 65.5 vs. 68.7 at 3-mth, and 68.2 vs. 75.3 at 24-mth FU, respectively. Mean PF in pts with TRMB vs. those without TRMB was 70.6 vs. 76.0 at RaC, 84.0 vs. 86.5 at 3-mth, and 89.2 vs. 93.2 at 24-mth FU, respectively. Mean FA in pts with TRMB vs. those without TRMB was 55.7 vs. 49.0 at RaC, 36.0 vs. 32.8 at 3-mth, and 31.8 vs. 22.9 at 24-mth, respectively. Similar results were seen at other visits. The GH/QL and PF score distributions showed lower first quartile in pts with TRMB vs. those without TRMB, suggesting that more pts with TRMB generally reported poorer PROs (except at 36-mth for GH/QL, 6-mth and 12-mth FU for PF). A similar pattern was observed for FA, except at later FU. Multivariate analysis showed consistent results, with mean estimates generally lower (GH/QL and PF) or higher (FA) in the TRMB group than in pts without TRMB, and significant results for GH/QL at most timepoints.
Conclusion: These findings suggest the detrimental effect of TRMB on pts' HRQoL from the patient's perspective especially during the treatment period and early FU. Treatments with fewer TRMB events are not only relevant clinically but can also improve pts' experience in advanced stage cHL. These data validate TRMB during the treatment period as a clinically meaningful and patient-relevant endpoint.