Peer-Reviewed Journal Details
Mandatory Fields
O'Dwyer, M;Henderson, R;Naicker, SD;Cahill, MR;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;Ryan, AE
2019
June
Blood Advances
CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study
Published
Optional Fields
TUMOR-ASSOCIATED MACROPHAGES WEEKLY BORTEZOMIB DARATUMUMAB DEXAMETHASONE MYELOMA LENALIDOMIDE PHAGOCYTOSIS REPERTOIRE EXPRESSION CANCER
3
12
1815
1825
Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase lb 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/m(2)), cyclophosphamide (150-300 mg/m(2)), 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 doselimiting 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-totreat/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.
2473-9529
10.1182/bloodadvances.2019000010
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