TY - JOUR
T1 - Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL
AU - van der Straten, Lina
AU - Stege, Claudia A.M.
AU - Kersting, Sabina
AU - Nasserinejad, Kazem
AU - Dubois, Julie
AU - Dobber, Johan A.
AU - Mellink, Clemens H.M.
AU - van der Kevie-Kersemaekers, Anne Marie F.
AU - Evers, Ludo M.
AU - de Boer, Fransien
AU - Koene, Harry R.
AU - Schreurs, John
AU - van der Klift, Marjolein
AU - Velders, Gerjo A.
AU - van der Spek, Ellen
AU - van der Straaten, Hanneke M.
AU - Hoogendoorn, Mels
AU - van Gelder, Michel
AU - Posthuma, Eduardus F.M.
AU - Visser, Hein P.J.
AU - Houtenbos, Ilse
AU - Idink, Cecile A.M.
AU - Issa, Djamila E.
AU - Dompeling, Ellen C.
AU - van Zaanen, Henk C.T.
AU - Veelken, J. Hendrik
AU - Levenga, Henriette
AU - Tick, Lidwine W.
AU - Terpstra, Wim E.
AU - Tonino, Sanne H.
AU - Westerweel, Peter E.
AU - Langerak, Anton W.
AU - Kater, Arnon P.
AU - Levin, Mark David
AU - Beckers, M. M.J.
AU - Bekker, A.
AU - Bellido, M.
AU - de Boer, F.
AU - Broers, R.
AU - Chamuleau, M.
AU - Croockewit, A. J.
AU - Dompeling, E. C.
AU - Eefting, M.
AU - Hoogendoorn, M.
AU - Doorduijn, J. K.
AU - Droogendijk, J.
AU - van der Griend, R.
AU - de Heer, K.
AU - HOVON CLL Working Group
N1 - Funding Information:
This study was funded by F. Hoffmann-La Roche ( ML29995 ).
Publisher Copyright:
© 2023 The American Society of Hematology
PY - 2023/9/28
Y1 - 2023/9/28
N2 - 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.
AB - 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.
U2 - 10.1182/blood.2023020195
DO - 10.1182/blood.2023020195
M3 - Article
C2 - 37363833
SN - 0006-4971
VL - 142
SP - 1131
EP - 1142
JO - Blood
JF - Blood
IS - 13
ER -