Evidence map›Paper›PMID 34915592›Full record

Trial reportBritish journal of haematology2022

Zanubrutinib for treatment-naïve and relapsed/refractory chronic lymphocytic leukaemia: long-term follow-up of the phase I/II AU-003 study.

Gavin Cull, Jan A Burger, Stephen Opat, David Gottlieb, Emma Verner, Judith Trotman, Paula Marlton, Javier Munoz, Patrick Johnston, David Simpson and 6 more

Registry-linked trialAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of haematology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02343120 (A Phase I/II, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects With B-Cell Lymphoid Malignancies), which is not on this map. Cited by 24 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 3 pooled it
–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.

NCT02343120 phase1 / phase2completednot on this map

A Phase I/II, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects With B-Cell Lymphoid Malignancies

TypeinterventionalSponsorBeiGeneRan2014 to 2021Enrolled385ConditionsB-cell MalignanciesArmsZanubrutinib
3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 3 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

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

16 authors.

Gavin CullSir Charles Gairdner Hospital, Perth, WA, Australia.
Jan A BurgerDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-6177-7572
Stephen OpatMonash Health, Clayton, VIC, Australia.
David GottliebFaculty of Medicine and Health, University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
Emma VernerConcord Repatriation Hospital, Concord, NSW, Australia.
Judith TrotmanConcord Repatriation Hospital, Concord, NSW, Australia.
Paula MarltonPrincess Alexandra Hospital, Brisbane, QLD, Australia.
Javier MunozBanner MD Anderson Cancer Center, Gilbert, AZ, USA.
Patrick JohnstonDivision of Hematology, Mayo Clinic, Rochester, MN, USA.
David SimpsonNorth Shore Hospital, Auckland, New Zealand.
Jennifer C SternBeiGene USA, Inc, San Mateo, CA, USA.
Radha PrathikantiBeiGene USA, Inc, San Mateo, CA, USA.
Kenneth WuBeiGene USA, Inc, San Mateo, CA, USA.
William NovotnyBeiGene USA, Inc, San Mateo, CA, USA.
Jane HuangBeiGene USA, Inc, San Mateo, CA, USA.
Constantine S TamPeter MacCallum Cancer Centre, Melbourne, VIC, Australia.ORCID 0000-0002-9759-5017

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The phase I/II AU-003 study in patients with treatment-naïve (TN) or relapsed/refractory (R/R) chronic lymphocytic leukaemia/small lymphocytic lymphoma demonstrated that zanubrutinib therapy results in clinically meaningful and durable responses with acceptable safety and tolerability. We report updated safety and efficacy data for 123 patients with a median follow-up of 47·2 months. Patients received zanubrutinib 160 mg twice daily (81 patients), 320 mg once daily (40), or 160 mg once daily (two). Discontinuations due to adverse events or disease progression were uncommon. The overall response rate (ORR) was 95·9% (TN, 100%; R/R, 95%) with 18·7% achieving complete response (CR). Ongoing response at 3 years was reported in 85·7%. The ORR in patients with del(17p)/tumour protein p53 mutation was 87·5% (CR 16·7%). The 2- and 3-year progression-free survival estimates were 90% (TN, 90%; R/R, 91%) and 83% (TN, 81%; R/R, 83%) respectively. The most reported Grade ≥3 adverse events were neutropenia (15·4%), pneumonia (9·8%), hypertension (8·9%) and anaemia (6·5%). The annual incidence of atrial fibrillation, major haemorrhage, Grade ≥3 neutropenia and Grade ≥3 infection decreased over time. With a median follow-up of ~4 years, responses remain clinically meaningful and durable and long-term tolerability to zanubrutinib therapy continues.

Indexed as

AdultAgedAged, 80 and overAntineoplastic AgentsFemaleFollow-Up StudiesHumansLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedNeoplasm Recurrence, LocalPiperidinesProgression-Free SurvivalPyrazolesPyrimidinesTreatment OutcomeAntineoplastic AgentsPiperidinesPyrazolesPyrimidineszanubrutinibBruton tyrosine kinasechromosome 17p deletionchronic lymphocytic leukaemiasmall lymphocytic lymphomazanubrutinib

Identifiers

PMID34915592
PMCPMC9300083

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.