CyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

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dc.contributor.author O'Dwyer, M.
dc.contributor.author Henderson, R.
dc.contributor.author Naicker, S.D.
dc.contributor.author Cahill, Mary R.
dc.contributor.author Murphy, P.
dc.contributor.author Mykytiv, C.
dc.contributor.author McEllistrim, C.
dc.contributor.author Krawczyk, J.
dc.contributor.author Walsh, J.
dc.contributor.author Lenihan, E.
dc.contributor.author Kenny, T.
dc.contributor.author Hernando, A.
dc.contributor.author Hirakata, G.
dc.contributor.author Parker, I.
dc.contributor.author Kinsella, E.
dc.contributor.author Gannon, G.
dc.contributor.author Natoni, A.
dc.contributor.author Lynch, K.
dc.contributor.author Ryan, A. E.
dc.date.accessioned 2019-09-17T13:59:03Z
dc.date.available 2019-09-17T13:59:03Z
dc.date.issued 2019-06-14
dc.identifier.citation O’Dwyer, M., Henderson, R., Naicker, S. D., Cahill, M. R., Murphy, P., Mykytiv, V., Quinn, J., McEllistrim, C., Krawczyk, J., Walsh, J., Lenihan, E., Kenny, T., Hernando, A., Hirakata, G., Parker, I., Kinsella, E., Gannon, G., Natoni, A., Lynch, K. and Ryan, A. E. (2019) 'CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study', Blood Advances, 3(12), pp. 1815-1825. (11pp.) DOI: 10.1182/bloodadvances.2019000010 en
dc.identifier.volume 3 en
dc.identifier.issued 12 en
dc.identifier.startpage 1815 en
dc.identifier.endpage 1825 en
dc.identifier.uri http://hdl.handle.net/10468/8546
dc.identifier.doi 10.1182/bloodadvances.2019000010 en
dc.description.abstract CyBorD DARA as induction is well tolerated and induces deep responses when used in conjunction with ASCT for MM.Mechanism of action studies indicate that CyBorD DARA enhances macrophage activation, which may play a role in its clinical efficacy. Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810. en
dc.description.sponsorship Irish Cancer Society (CRF12RYA) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher American Society of Hematology en
dc.relation.uri http://www.bloodadvances.org/content/3/12/1815
dc.rights ©2019 by The American Society of Hematology en
dc.subject CyBorD-DARA en
dc.subject Daratumumab (DARA) en
dc.subject Multiple myeloma (MM) en
dc.subject Autologous stem cell transplantation (ASCT) en
dc.title CyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Mary Cahill, Pathology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: mary.cahill@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Irish Cancer Society en
dc.contributor.funder Janssen Research and Development en
dc.contributor.funder National University of Ireland, Galway en
dc.contributor.funder European Regional Development Fund en
dc.contributor.funder Government of Ireland en
dc.contributor.funder Galway University Foundation en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Blood Advances en
dc.internal.IRISemailaddress mary.cahill@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Starting Investigator Research Grant (SIRG)/15/SIRG/3456/IE/'RESTRAIN' Investigation of tumour stromal interactions in metastatic colon cancer for the identification of novel immuno-therapeutic targets/ en
dc.relation.project info:eu-repo/grantAgreement/SFI/ICS-SFI Collaborative Cancer Research Centre (CCRC) Programme/14/ICS/B3042/IE/Irish Blood Cancer Network (IBCN)/ en
dc.identifier.eissn 2473-9529


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