Impact of PET‐2 guided treatment de‐escalation on time‐to‐recovery from cancer‐related fatigue in advanced stage Hodgkin Lymphoma: results from the GHSG HD18 study

Abstract

Introduction: Persisting cancer related fatigue (CRF) has impact on health related quality of life (HRQoL) and social re-integration of patients with Hodgkin lymphoma (HL). The GHSG HD18 trial established treatment PET-2 guided de-escalation of treatment for advanced-stage HL as new standard. Here, we investigate the impact of treatment de-escalation in HD18 on long-term HRQoL domains and time-to-recovery from fatigue (TTR-F). Methods: Mean fatigue scores (FA) of the EORTC QLQ-C30 questionnaire are reported descriptively for baseline, interim, end-of-treatment, and yearly follow-up. TTR-F was defined as time from end of chemotherapy until first occurrence of FA <30 or the time of last questionnaire (censored). TTR-F was analyzed and compared using time-to-event methods including cumulative incidence and cox proportional hazard models, as recommended by the SISAQoL consortium. Effect of disease, patient and treatment characteristics on 2y HRQoL domains was analyzed using multiple regression. Results: 2101 patients aged 18–60 years with advanced-stage HL were recruited in HD18, of whom 156 were found ineligible before or after randomization. PET-2 negative Patients were randomized between 8x eBEACOPP (arm C, n = 288) and 4x eBEACOPP (arm D; n = 285), and between 6x eBEACOPP (arm C6; n = 216) and 4x eBEACOPP (D4; n = 216). HRQoL questionnaires at baseline were available in 83.9% of all randomized patients. Overall, baseline FA and age were significantly associated with TTR-F, whereas sex was not. TTR-F differed between trial arms for PET-2 negative, but not for PET-2 positive patients. Particularly, treatment reduction from 8 to 4 cycles of eBEACOPP led to a significantly shorter TTR-F (HR 1.41, p = 0.008). Reducing the cycle number of eBEACOPP from 8 to 6 cycles (HR 1.21, p = 0.2) or 6 to 4 cycles (HR 1.22, p = 0.18) speeded TTR-F accordingly but was not statistically significant. For PET-positive patients a significantly slower TTR-F was observed with addition of Rituximab (HR 0.7, p = 0.0163). In PET-2-negative patients, median TTR-F was 19 months (CI95: 13–28) in arm C, 13 months (CI95: 10–20) in arm C6, 12 months (CI95: 8–15) in arm D and 10 months (CI95: 8–13) arm D4. HRQoL at baseline and age were the main determinants of 2y HRQoL domains. The research was funded by: Deutsche Krebshilfe, Swiss State Secretariat for Education and Research, and Roche Pharma AG. Keywords: Chemotherapy, Hodgkin lymphoma, Late Effects in Lymphoma Survivors No conflicts of interests pertinent to the abstract.