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Teclistamab Shows Potential Activity in BCMA-Positive MM
Data support further examination of teclistamab therapy in the context of patients with multiple myeloma (MM) and BCMA expression (Blood Adv. 2020;4[18]:4538-4549).
“We developed a BCMAxCD3 bispecific antibody (teclistamab [JNJ-64007957]) to recruit and activate T cells to kill BCMA-expressing MM cells,” the researchers wrote.
The active T cell-redirecting bispecific antibody, teclistamab, was shown to induce cytotoxicity in BCMA-positive MM cell lines in vitro (H929 cells, 50% effective concentration [EC50] = 0.15 nM; MM.1R cells, EC50 = 0.06 nM; RPMI 8226 cells, EC50 = 0.45 nM) with parallel T-cell activation (H929 cells, EC50 = 0.21 nM; MM.1R cells, EC50 = 0.1 nM; RPMI 8226 cells, EC50 = 0.28 nM) and cytokine release. When a γ-secretase inhibitor (LY-411575) was present, this activity increased.
In addition, ex vivo assay findings from the bone marrow samples of patients with MM and an average EC50 value of 1.7 nM showed that teclistamab depleted BCMA-positive cells.
Furthermore, teclistamab mediated dose-dependent lysis of H929 cells and activation of T-cells in more physiologic conditions using healthy human whole blood.
Teclistamab also yielded antitumor activity in 2 BCMA-positive MM murine xenograft models inoculated with human T-cells when compared with vehicle and antibody controls.
“The specific and potent activity of teclistamab against BCMA-expressing cells from MM cell lines, patient samples, and MM xenograft models warrant further evaluation of this bispecific antibody for the treatment of MM,” the investigators concluded.
“Phase 1 clinical trials…are ongoing for patients with relapsed/refractory MM,” they added.—Hina M. Porcelli
