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dc.contributor.authorRamchandren, R
dc.contributor.authorJohnson, P
dc.contributor.authorGhosh, N
dc.contributor.authorRuan, J
dc.contributor.authorArdeshna, KM
dc.contributor.authorJohnson, R
dc.contributor.authorVerhoef, G
dc.contributor.authorCunningham, D
dc.contributor.authorde Vos, S
dc.contributor.authorKassam, S
dc.contributor.authorFayad, L
dc.contributor.authorRadford, J
dc.contributor.authorBailly, S
dc.contributor.authorOffner, F
dc.contributor.authorMorgan, D
dc.contributor.authorMunoz, J
dc.contributor.authorPing, J
dc.contributor.authorSzafer-Glusman, E
dc.contributor.authorEckert, K
dc.contributor.authorNeuenburg, JK
dc.contributor.authorGoy, A
dc.coverage.spatialEngland
dc.date.accessioned2023-04-12T10:30:07Z
dc.date.available2023-04-12T10:30:07Z
dc.date.issued2023-02-01
dc.identifier101779
dc.identifierS2589-5370(22)00508-9
dc.identifier.citationEClinicalMedicine, 2023, 56 pp. 101779 -en_US
dc.identifier.issn2589-5370
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5751
dc.identifier.eissn2589-5370
dc.identifier.eissn2589-5370
dc.identifier.doi10.1016/j.eclinm.2022.101779
dc.description.abstractBACKGROUND: This phase 1b/2 PCYC-1123-CA study evaluated efficacy and safety of the combination of ibrutinib, lenalidomide, and rituximab (iR2 regimen) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem cell transplantation. METHODS: In phase 2, patients with relapsed/refractory non-germinal centre B-cell-like DLBCL received oral ibrutinib 560 mg once daily and oral lenalidomide 20 mg or 25 mg once daily on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity and intravenous rituximab 375 mg/m2 on Day 1 of Cycles 1-6. The primary endpoint was overall response rate (ORR) in the response-evaluable population (received any study treatment and had ≥1 post-baseline disease assessment). The study was done at 24 academic and community hospitals in Belgium, Germany, United Kingdom, and USA. This study was registered with ClinicalTrials.gov, NCT02077166. FINDINGS: Between March 13, 2014 and October 2, 2018, 89 patients were enrolled with a median time on study of 35.0 months. Best ORR in the response-evaluable population (n = 85) was 49% (95% confidence interval [CI], 38-61) across dose cohorts and 53% (95% CI, 39-67) and 44% (95% CI, 26-62) in the 20 mg and 25 mg lenalidomide cohorts, respectively, with complete responses in 24/85 (28%), 17/53 (32%), and 7/32 (22%) patients, respectively. Grade 3/4 adverse events (AEs) occurred in 81/89 patients (91%), most frequently neutropenia (36/89; 40%), maculopapular rash (16/89; 18%), anaemia (12/89; 13%), and diarrhoea (9/89; 10%). Serious adverse events occurred in 57/89 patients (64%). Fatal AEs occurred in 12/89 patients (13%); causes of death were worsening of DLBCL (n = 7), pneumonia (n = 3), sepsis (n = 1), and cardiac arrest (n = 1). INTERPRETATION: The most frequent AEs (diarrhoea, neutropenia, fatigue, cough, anaemia, peripheral oedema, and maculopapular rash) were consistent with known safety profiles of the individual drugs. The iR2 regimen demonstrated antitumour activity with durable responses in patients with relapsed/refractory DLBCL. FUNDING: Pharmacyclics LLC, an AbbVie Company.
dc.formatElectronic-eCollection
dc.format.extent101779 -
dc.languageeng
dc.language.isoengen_US
dc.publisherElsevier BVen_US
dc.relation.ispartofEClinicalMedicine
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectDiffuse large B-cell lymphoma
dc.subjectIbrutinib
dc.subjectLenalidomide
dc.subjectRituximab
dc.titleThe iR2 regimen (ibrutinib plus lenalidomide and rituximab) for relapsed/refractory DLBCL: A multicentre, non-randomised, open-label phase 2 study.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-11-22
dc.date.updated2023-04-12T10:29:34Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1016/j.eclinm.2022.101779en_US
rioxxterms.licenseref.startdate2023-02-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/36618900
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.publication-statusPublished online
pubs.publisher-urlhttp://dx.doi.org/10.1016/j.eclinm.2022.101779
pubs.volume56
icr.researchteamMedicine (RMH)en_US
dc.contributor.icrauthorCunningham, David
icr.provenanceDeposited by Mr Arek Surman on 2023-04-12. Deposit type is initial. No. of files: 1. Files: The iRsup2sup regimen (ibrutinib plus lenalidomide and rituximab) for relapsedrefractory DLBCL A multicentre, non-randomised.pdf


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