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 Visser; Ilse 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

doi:10.1182/blood.2023020195

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 Visser

Ilse 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

Cancer Center Amsterdam (CCA)
Haga Ziekenhuis
Amsterdam UMC
VU University Medical Center
Ikazia Hospital
St. Antonius Ziekenhuis
Martini Ziekenhuis
Amphia Hospital
Gelderse Vallei Hospital
Rijnstate Hospital
St. Jansdal Hospital
Medical Centre Leeuwarden
Maastricht University Medical Centre
Leiden University Medical Centre
Northwest Clinics Alkmaar
Spaarne Gasthuis
Bravis Hospital/ZorgSaam Hospital Zeeuws-Vlaanderen
Jeroen Bosch Ziekenhuis
Isala Clinics
Franciscus Gasthuis & Vlietland
Groene Hart Hospital
Maxima Medical Centre
Onze Lieve Vrouwe Gasthuis

Research output: Contribution to journal › Article › Academic › peer-review

28 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 language	English
Pages (from-to)	1131-1142
Number of pages	12
Journal	Blood
Volume	142
Issue number	13
Early online date	28 Jun 2023
DOIs	https://doi.org/10.1182/blood.2023020195
Publication status	Published - 28 Sept 2023

Bibliographical note

Publisher Copyright:
© 2023 The American Society of Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1182/blood.2023020195

https://hdl.handle.net/11370/4552a5e4-6c46-43ea-8fb2-60d21e264713Licence: Article 25fa Dutch Copyright Act

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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., ... Levin, M.-D. (2023). Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL. Blood, 142(13), 1131-1142. https://doi.org/10.1182/blood.2023020195

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

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{\textquoteright} 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.",

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

note = "Publisher Copyright: {\textcopyright} 2023 The American Society of Hematology",

year = "2023",

month = sep,

day = "28",

doi = "10.1182/blood.2023020195",

language = "English",

volume = "142",

pages = "1131--1142",

journal = "Blood",

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Van Der Straten, L, Stege, CAM, Kersting, S, Nasserinejad, K, Dubois, J, Dobber, JA, Mellink, CHM, van der Kevie-Kersemaekers, A-MF, Evers, LM, de Boer, F, Koene, HR, Schreurs, J, van der Klift, M, Velders, GA, van der Spek, E, van der Straaten, HM, Hoogendoorn, M, Van Gelder, M, Posthuma, EFM, Visser, HPJ, Houtenbos, I, Idink, CAM, Issa, DE, Dompeling, EC, van Zaanen, HCT, Veelken, H, Levenga, H, Tick, LW, Terpstra, WE, Tonino, SH, Westerweel, PE, Langerak, AW , Kater, AP & Levin, M-D 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

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, Hanna 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, 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

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.

UR - https://www.scopus.com/pages/publications/85165309851

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 -

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

Abstract

Bibliographical note

UN SDGs

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