Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit CLL patients.

Chronic lymphocytic leukemia (CLL)-related symptoms and morbidity related to the advanced age at diagnosis, impairs the well-being of older CLL patients. Therefore, it is essential to tailor treatment according to geriatric characteristics and aim for an improvement in health-related quality of life (HRQoL) as a primary treatment goal. In the HOVON139/GiVe trial, 12 cycles of fixed-duration venetoclax plus obinutuzumab (Ven-O) was shown to be effective and tolerable in previously untreated CLL patients (n=67) who were unfit for fludarabine, cyclophosphamide and rituximab (FCR). However, prolonged venetoclax exposure as consolidation treatment led to increased toxicity with limited effect on minimal residual disease (MRD). To assess the impact of geriatric assessment on treatment outcomes and the patients' HRQoL, patient reported outcomes (PRO) including function, depression, cognition, nutrition, physical performance, muscle parameters, comorbidities and the European Organization for Research and Treatment of Cancer (EORTC) C30 and CLL17 questionnaires were assessed. At baseline, geriatric impairments were present in >90% of patients and ≥2 impairments, present in 60% of patients, predicted grade ≥3 non-hematological toxicity. During treatment, the number of geriatric impairments diminished significantly and clinical relevant improvements in HRQoL subscales were reached for global health status, physical functioning, role functioning, emotional functioning, fatigue, dyspnea, physical condition/fatigue and worries/fears related to health and functioning. These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued (93% based on negative MRD in MRD-guided arm). Collectively, front-line fixed-duration Ven-O improves overall PROs in older, unfit CLL patients with and without geriatric impairments.