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

Lina Van Der Straten, Claudia A M Stege, Sabina Kersting, Kazem Nasserinejad, Julie Dubois, Johan A Dobber, Clemens H M Mellink, Anne-Marie F van der Kevie-Kersemaekers, Ludo M Evers, Fransien de Boer, Harry R Koene, John Schreurs, Marjolein van der Klift, Gerjo A Velders, Ellen van der Spek, Hanna M van der Straaten, Mels Hoogendoorn, Michel Van Gelder, Eduardus F M Posthuma, Hein P J VisserIlse Houtenbos, Cecile A M Idink, Djamila E Issa, Ellen C Dompeling, Henk C T van Zaanen, Hendrik Veelken, Henriette Levenga, Lidwine W Tick, Wim E Terpstra, Sanne H Tonino, Peter E Westerweel, Anton W Langerak, Arnon P Kater, Mark-David Levin

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)1131-1142
Number of pages12
JournalBlood
Volume142
Issue number13
Early online date28 Jun 2023
DOIs
Publication statusPublished - 28 Sept 2023

Bibliographical note

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© 2023 The American Society of Hematology

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