Patient-Reported Chemotherapy-Induced Peripheral Neuropathy (CIPN) in Advanced-Stage Classical Hodgkin Lymphoma Treated with BrECADD and eBEACOPP in the HD21 Trial
Authors: Kristo Fjoralba , Mazerolle Flora , Alin Thibaud , Regnault Antoine , Ferdinandus Justin , Behringer Karolin , Jablonski Janina , Borchmann Peter , Ashaye Ajibade 
Published: December 2024

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients (pts) treated with chemotherapy and can manifest through sensory, motor, and autonomic neuropathy symptoms. Sensory symptoms are usually predominant, typically affecting the hands and feet simultaneously, with a risk of CIPN late effects as survival rates continue to improve. In the ongoing German Hodgkin Study Group (GHSG) HD21 study, a phase 3 open-label randomized trial, BrECADD showed better tolerability compared to escalated BEACOPP (eBEACOPP) as first-line treatment of newly diagnosed advanced-stage classical Hodgkin lymphoma (cHL). This exploratory post-hoc analysis describes pts' experience of CIPN sensory symptoms in patients treated with BrECADD vs. eBEACOPP.
Methods: The study randomized 1,500 pts (1:1) to receive BrECADD or eBEACOPP in 4-6, 21-day, treatment cycles. The patient-reported outcome (PRO) European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire - Core 30 items (QLQ-C30) and Quality of Life Questionnaire - 20-item Chemotherapy-Induced Peripheral Neuropathy module (QLQ-CIPN20) were administered at baseline, during the treatment period (4 to 6 cycles) and follow-up (FU) period up to 60 months (mth)s. Responses to the QLQ-CIPN20 items were described at each visit across treatment arms. The impact of CIPN on health-related quality of life was explored by describing the QLQ-C30 global health/quality of life (GH/QL), identified as a key concept, across groups defined by pts who reported sensory symptoms vs. those who did not at each visit.
Results: The PRO analysis set - all pts with a baseline PRO and at least one postbaseline PRO from the intent-to-treat population included 360 pts in BrECADD and 372 pts in eBEACOPP, with similar baseline characteristics across arms (mean age of 34 vs. 35 years, and 53% vs. 56% male in BrECADD vs. eBEACOPP respectively).
CIPN-related tingling in fingers/hands, tingling in toes/feet, numbness in fingers, and numbness in toes were the most experienced symptoms by pts in both arms, with a trend toward fewer pts in BrECADD. Pts' experience of these symptoms showed a similar pattern in both arms, with an increased proportion of pts reporting these symptoms mostly during the treatment period before a slight decrease over the FU. Tingling in fingers/hands was reported by 56% vs. 64% of pts at restaging after chemotherapy (RaC), 54% vs. 45% at 3-mth, and 37% vs. 40% at 6-mth FU in BrECADD vs. eBEACOPP, respectively. Similarly, tingling in toes/feet was reported by 30% vs. 46% of pts at RaC, 34% vs. 40% at 3-mth, and 28% vs. 33% at 6-mth in BrECADD vs. eBEACOPP, respectively. A similar pattern was observed for numbness in fingers and numbness in toes.
Pts with CIPN-related sensory symptoms also tended to report poorer overall health: at RaC, mean GH/QL score was 57.9 vs. 53.1 in pts who experienced vs. those who did not experience tingling in fingers/hands, 58.1 vs. 50.0 in pts with vs. those without tingling in toes/feet, 59.7 vs. 51.2 in pts with vs. those without numbness in fingers, and 58.0 vs. 48.9 in pts with vs. without numbness in toes. Similar results were observed at other timepoints.
Conclusion: CIPN-related sensory symptoms were experienced in both treatment arms, and symptoms related to lower extremities generally occurred less frequently with BrECADD. Pts who experienced these sensory symptoms also tended to report poorer overall health. This suggests that multiagent regimen treatments for newly diagnosed advanced-stage cHL associated with fewer CIPN-related sensory symptoms could also lead to improved overall health.