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.authorO'Dwyer, M.
dc.contributor.authorHenderson, R.
dc.contributor.authorNaicker, S.D.
dc.contributor.authorCahill, Mary R.
dc.contributor.authorMurphy, P.
dc.contributor.authorMykytiv, C.
dc.contributor.authorMcEllistrim, C.
dc.contributor.authorKrawczyk, J.
dc.contributor.authorWalsh, J.
dc.contributor.authorLenihan, E.
dc.contributor.authorKenny, T.
dc.contributor.authorHernando, A.
dc.contributor.authorHirakata, G.
dc.contributor.authorParker, I.
dc.contributor.authorKinsella, E.
dc.contributor.authorGannon, G.
dc.contributor.authorNatoni, A.
dc.contributor.authorLynch, K.
dc.contributor.authorRyan, A. E.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderIrish Cancer Societyen
dc.contributor.funderJanssen Research and Developmenten
dc.contributor.funderNational University of Ireland, Galwayen
dc.contributor.funderEuropean Regional Development Funden
dc.contributor.funderGovernment of Irelanden
dc.contributor.funderGalway University Foundationen
dc.date.accessioned2019-09-17T13:59:03Z
dc.date.available2019-09-17T13:59:03Z
dc.date.issued2019-06-14
dc.description.abstractCyBorD 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.sponsorshipIrish Cancer Society (CRF12RYA)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO’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.2019000010en
dc.identifier.doi10.1182/bloodadvances.2019000010en
dc.identifier.eissn2473-9529
dc.identifier.endpage1825en
dc.identifier.issued12en
dc.identifier.journaltitleBlood Advancesen
dc.identifier.startpage1815en
dc.identifier.urihttps://hdl.handle.net/10468/8546
dc.identifier.volume3en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.projectinfo: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.projectinfo:eu-repo/grantAgreement/SFI/ICS-SFI Collaborative Cancer Research Centre (CCRC) Programme/14/ICS/B3042/IE/Irish Blood Cancer Network (IBCN)/en
dc.relation.urihttp://www.bloodadvances.org/content/3/12/1815
dc.rights©2019 by The American Society of Hematologyen
dc.subjectCyBorD-DARAen
dc.subjectDaratumumab (DARA)en
dc.subjectMultiple myeloma (MM)en
dc.subjectAutologous stem cell transplantation (ASCT)en
dc.titleCyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 studyen
dc.typeArticle (peer-reviewed)en
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