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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Date
2019-06-14
Authors
O'Dwyer, M.
Henderson, R.
Naicker, S.D.
Cahill, Mary R.
Murphy, P.
Mykytiv, C.
McEllistrim, C.
Krawczyk, J.
Walsh, J.
Lenihan, E.
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American Society of Hematology
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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.
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Keywords
CyBorD-DARA , Daratumumab (DARA) , Multiple myeloma (MM) , Autologous stem cell transplantation (ASCT)
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
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©2019 by The American Society of Hematology