Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL
Publication date
2023-09-28
Authors
van der Straten, Lina
Stege, Claudia A.M.
Kersting, Sabina
Nasserinejad, Kazem
Dubois, Julie
Dobber, Johan A.
Mellink, Clemens H.M.
van der Kevie-Kersemaekers, Anne Marie F.
Evers, Ludo M.
de Boer, Fransien
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Supervisors
Document Type
Article
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taverne
Abstract
Chronic lymphocytic leukemia (CLL)–related symptoms and morbidity related to the advanced age at diagnosis impairs the well-being of older adult 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) were shown to be effective and tolerable in FCR (fludarabine, cyclophosphamide, rituximab)-unfit patients with CLL (n = 67). However, prolonged venetoclax exposure as consolidation treatment led to increased toxicity with limited effect on minimal residual disease. To assess the impact of geriatric assessment on treatment outcomes and the patients’ HRQoL, patient-reported outcomes (PROs), including function, depression, cognition, nutrition, physical performance, muscle parameters, comorbidities, and the European Organization for Research and Treatment of Cancer 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 nonhematological toxicity. During treatment, the number of geriatric impairments diminished significantly and clinically relevant improvements in HRQoL subscales were reached for global health status, physical functioning, role functioning, emotional functioning, fatigue, dyspnea, physical condition or fatigue, and worries or fears related to health and functioning. These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued. Collectively, frontline fixed-duration Ven-O improves overall PROs in older, unfit patients with CLL with and without geriatric impairments. This study was registered at EudraCT as 2015-004985-27 and the Netherlands Trial Register as NTR6043.
Keywords
Humans, Aged, Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis, Quality of Life, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bridged Bicyclo Compounds, Heterocyclic/adverse effects, Fatigue/chemically induced, Taverne, Biochemistry, Immunology, Hematology, Cell Biology, Journal Article
Citation
van der Straten, L, Stege, C A M, Kersting, S, Nasserinejad, K, Dubois, J, Dobber, J A, Mellink, C H M, van der Kevie-Kersemaekers, A M F, Evers, L M, de Boer, F, Koene, H R, Schreurs, J, van der Klift, M, Velders, G A, van der Spek, E, van der Straaten, H M, Hoogendoorn, M, van Gelder, M, Posthuma, E F M, Visser, H P J, Houtenbos, I, Idink, C A M, Issa, D E, Dompeling, E C, van Zaanen, H C T, Veelken, J H, Levenga, H, Tick, L W, Terpstra, W E, Tonino, S H, Westerweel, P E, Langerak, A W, Kater, A P, Levin, M D, Beckers, M M J, Bekker, A, Bellido, M, de Boer, F, Broers, R, Chamuleau, M, Croockewit, A J, Dompeling, E C, van Gelder, M, van Kampen, R, Mous, R, te Raa, G D, Raymakers, R A P, Regelink, J C, Visser, H P J, Vos, J M I & HOVON CLL Working Group 2023, 'Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL', Blood, vol. 142, no. 13, pp. 1131-1142. https://doi.org/10.1182/blood.2023020195