Evidence map›Paper›PMID 41460718›Full record

ArticleHematological oncology2026

Clinical Frailty Scale as a Predictor of Early Treatment Discontinuation in Elderly Patients With Chronic Lymphocytic Leukemia Treated With Zanubrutinib: A Multicenter Real-World Study.

Ernesto Vigna, Enrica Antonia Martino, Annalisa Pitino, Raffaella Pasquale, Isacco Ferrarini, Riccardo Moia, Andrea Visentin, Alessandro Sanna, Marina Motta, Massimo Moratti and 75 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Hematological oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

85 authors.

Ernesto VignaDepartment of Onco-Hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Enrica Antonia MartinoDepartment of Onco-Hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Annalisa PitinoInstitute of Clinical Physiology (IFC-CNR), Rome, Italy.
Raffaella PasqualeAzienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologia, Udine, Italy.
Isacco FerrariniDepartment of Engineering for Innovation Medicine, University of Verona, Verona, Italy.
Riccardo MoiaDivision of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.ORCID https://orcid.org/0000-0001-7393-1138
Andrea VisentinHematology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Alessandro SannaHematology Unit, Deparment of Oncology, AOU-Careggi, Florence, Italy.ORCID https://orcid.org/0000-0002-5015-381X
Marina MottaDepartment of Hematology, ASST Spedali Civili di Brescia, Lombardia, Italy.
Massimo MorattiAzienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologia, Udine, Italy.
Paolo SportolettiCentro di Ricerca Emato-Oncologica (CREO), Dipartimento di Medicina e Chirurgia Università di Perugia, Perugia, Italy.ORCID https://orcid.org/0000-0002-5630-9862
Annalisa ChiarenzaDivision of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy.
Alessandro MaggiHaematology, Ospedale G. Moscati, Taranto, Italy.
Valentina ZammitOncoematology and BMT Unit, Oncology Department Ospedale La Maddalena Palermo, Palermo, Italy.
Michele MerliHematology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
Idanna InnocentiDipartimento di Scienze di Laboratorio ed Ematologiche, Area Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Claudia GiordanoDepartment of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.
Laura NocilliDepartment of Hematology, Azienda Ospedaliera Papardo, Messina, Italy.
Massimiliano PostorinoHematology Department of Biomedicine and Prevention Tor Vergata University of Rome, Rome, Italy.
Caterina StelitanoDepartment of Hematology, Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
Andrea FerrarioDepartment of Medicine and Surgery, University of Insubria and Department of Oncology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy.
Anna Maria FrustaciDepartment of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.ORCID https://orcid.org/0000-0003-2587-7901
Marcello RivaHematology Department, Ospedale San Bortolo di Vicenza, Vicenza, Italy.
Sara PepeHematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
Adalberto IbaticiHematology and Cellular Therapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Stefania ScardinoHematology and Stem Cell Transplant Unit, "Vito Fazzi" Hospital, Lecce, Italy.
Paola Anticoli BorzaUOC Ematologia, Azienda Ospedaliera San Giovanni-Addolorata, Rome, Italy.
Laura BallottaDipartimento Clinico di Scienze Mediche, Chirurgiche e della Salute, Università degli Studi di Trieste, Trieste, Italy.ORCID https://orcid.org/0000-0003-2731-2074
Salvatrice MancusoDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Hematology Unit, University of Palermo, Palermo, Italy.
Francesco MalaspinaHematology Unit, IRCCS, IRST Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori "Dino Amadori", Meldola, Italy.
Anna MeleHaematology, Ospedale Cardinale Panico, Tricase(Lecce), Italy.
Sara GalimbertiDivision of Hematology, University Hospital of Pisa, Pisa, Italy.
Gioacchino CataniaSCDU Ematologia -AOU SS Antonio e Biagio e C. Arrigo., Alessandria, Italy.
Annamaria GiordanoUnit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Bari, Italy.
Ilaria AngelettiDepartment of Medicine and Surgery, University of Perugia, Hematology/Oncology Unit, Terni Hospital, Terni, Italy.
Luana SchiattoneDipartimento di Ematologia Clinica Ospedale civile S. Spirito Pescara, Pescara, Italy.
Elsa PenneseDipartimento di Ematologia Clinica Ospedale civile S. Spirito Pescara, Pescara, Italy.
Rosanna MiccolisDepartment of Hematology, ASL BT, Barletta, Italy.
Angelo FamaDepartment of Internal Medicine, Hematology Unit, Ospedale G. Mazzini, Teramo, Italy.
Giulio GiordanoUnità Operativa Complessa, Medicina Servizio e Ambulatorio di Ematologia Ospedale di Riferimento Regionale Antonio Cardarelli, Campobasso, Italy.
Catello CalifanoOnco-Hematology Unit, "A. Tortora" Hospital, Pagani, Italy.
Antonella BruzzeseDepartment of Onco-Hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Santino CasertaDepartment of Onco-Hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Giuliana FarinaHematology, Hospital "Sant'Anna e San Sebastiano", Caserta, Italy.
Pietro BulianCentro di Riferimento Oncologico di Aviano (CRO), Clinical and Experimental Onco-Hematology Unit, IRCCS, Aviano, Italy.
Giacomo LosetoHematology and Cell Therapy Unit, IRCCS Istituto Tumori 'Giovanni Paolo II', Bari, Italy.
Barbara PocaliDivision of Hematology and Stem Cell Transplantation Unit, Cardarelli Hospital, Naples, Italy.
Vanessa InnaoHematology Unit, Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione (ARNAS) Garibaldi, Catania, Italy.
Piero GalieniDepartment of Haematology and Stem Cell Transplantation Unit, C. e G. Mazzoni Hospital, Ascoli Piceno, Italy.
Vincenzo FraticelliDepartment of Hematology, Gemelli Molise, Campobasso, Italy.
Candida VitaleDivision of Hematology, A.O.U. Città della Salute e della Scienza di Torino, Turin, Italy.
Azzurra RomeoHematology Unit, Ospedale Santa Maria Goretti, Latina, Italy.
Marco RossiDepartment of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, Catanzaro, Italy.
Ilaria ScortechiniAzienda Ospedaliero Universitaria delle Marche, Ancona, Italy.
Federico VozellaHematology, Stem cell Transplantation, Fondazione Policlinico Universitario Campus Bio Medico di Roma, Rome, Italy.
Luigi MalandruccoloHematology Unit Ospedale "Fabrizio Spaziani", Frosinone, Italy.
Marzia VarettoniDivision of Hematology, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy.
Lucia MorelloUnità Operativa di Ematologia, Ospedale Guglielmo da Saliceto, Piacenza, Italy.
Giuseppe PietrantuonoIRCCS CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
Esmeralda ConteHaematology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University, Rome, Italy.
Martina CantelliUnità di Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy.
Roberta MurruHematology and Stem Cell Transplantation Unit, Ospedale Oncologico A. Businco, ARNAS G. Brotzu, Cagliari, Italy.
Daniele CaraccioloDepartment of Experimental and Clinical Medicine Magna Grecia University, Catanzaro, Italy.
Enrico DerenziniDivision of Onco-Hematology, IEO, European Institute of Oncology IRCCS, Milano, Italy.ORCID https://orcid.org/0000-0002-7154-8140
Valentina Di MartinaHematology Unit, Ospedale San Vincenzo, Taormina, Italy.
Roberto MarascaHematology Unit, Department of Oncology and Hematology Azienda-Ospedaliero Universitaria (AOU) of Modena, Policlinico Modena, Modena, Italy.
Maria Ilaria Del PrincipeHematology Department of Biomedicine and Prevention Tor Vergata University of Rome, Rome, Italy.
Amalia FigueraDivision of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy.
Francesco AngotziHematology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Marta CosciaDepartment of Medicine and Surgery, University of Insubria and Department of Oncology, ASST Sette Laghi, Ospedale di Circolo, Varese, Italy.
Nicola Di RenzoHematology and Stem Cell Transplant Unit, "Vito Fazzi" Hospital, Lecce, Italy.
Luca LaurentiDipartimento di Scienze di Laboratorio ed Ematologiche, Area Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Nicola AmodioDepartment of Experimental and Clinical Medicine Magna Grecia University, Catanzaro, Italy.
Pellegrino MustoUnit of Hematology and Stem Cell Transplantation, AOUC Policlinico, Bari, Italy.
Francesco Di RaimondoDivision of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy.
Arcangelo LisoDepartment of Medicine and Surgery, University of Perugia, Hematology/Oncology Unit, Terni Hospital, Terni, Italy.
Alessandra TedeschiDepartment of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Livio TrentinHematology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
Francesca Romana MauroHematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
Giovanni TripepiClinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, Institute of Clinical Physiology (IFC-CNR), Reggio Calabria, Italy.
Andrea CorsonelloUnit of Geriatric Medicine, Italian National Research Center on Aging (IRCCS INRCA), Cosenza, Italy.
Fortunato MorabitoAIL Sezione di Cosenza, Cosenza, Italy.
Valter GatteiCentro di Riferimento Oncologico di Aviano (CRO), Clinical and Experimental Onco-Hematology Unit, IRCCS, Aviano, Italy.
Massimo GentileDepartment of Onco-Hematology, Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.ORCID https://orcid.org/0000-0002-5256-0726

Funding

PNRR-MAD-2022-12375673 2022-12375673
6 · The paper itself

Abstract

The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65 years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1 years, range 65.1-94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56-0.73, p < 0.001). At 12 months, the discontinuation rate was significantly higher among patients with a CFS > 3 (29.2%) compared with those with a CFS ≤ 3 (8.8%) (p < 0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

Indexed as

Antineoplastic AgentsFrailtyLeukemia, Lymphocytic, Chronic, B-CellPiperidinesPyrazolesPyrimidinesAgedAged, 80 and overFemaleFollow-Up StudiesHumansMalePrognosisProspective StudiesAntineoplastic AgentsPiperidinesPyrazolesPyrimidineszanubrutinibchronic lymphocytic leukemiaclinical frailty scalefrailtytreatment discontinuationzanubrutinib

Identifiers

PMID41460718
PMCPMC12963948

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