Safety and Efficacy of B-Cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T Cells (CART-BCMA) with Cyclophosphamide Conditioning for Refractory Multiple Myeloma (MM)

Abstract

Abstract Background: CART-BCMA is an autologous T cell product engineered by lentiviral transduction to express a fully human BCMA-specific CAR with CD3ζ and 4-1BB signaling domains and expanded ex vivo using anti-CD3/anti-CD28 beads. We reported early safety and clinical activity of CART-BCMA without lymphodepleting chemotherapy in highly refractory MM patients (pts) (Cohen et al, ASH 2016, #1147). Here we report extended results from this initial cohort, as well as initial safety and efficacy in additional cohorts at 2 dose levels in conjunction with cyclophosphamide (Cy). Methods: Three cohorts are being enrolled: 1) 1-5 x 108 CART cells alone; 2) Cy 1.5 g/m2 + 1-5 x 107 CART cells; and 3) Cy 1.5 g/m2 + 1-5 x 108 CART cells. CART-BCMA cells are given as split-dose infusions (10% on day 0, 30% on day 1, and 60% on day 2), with Cy given on day -3. Pts need serum creatinine (Cr) Disclosures Cohen: Bristol Meyers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Celgene: Consultancy; Janssen: Consultancy. Lacey: Novartis: Research Funding; Genentech: Honoraria. Lancaster: Amgen: Consultancy; Janssen: Consultancy. Vogl: Karyopharm: Consultancy; Amgen: Consultancy; Teva: Consultancy; Calithera: Research Funding; GSK: Research Funding; Celgene: Consultancy; Takeda: Consultancy, Research Funding; Constellation: Research Funding. Weiss: Prothena: Research Funding; Alnylam: Honoraria; Janssen: Honoraria; Janssen: Research Funding; Prothena: Honoraria. Chen: Novartis: Research Funding. Young: Novartis: Research Funding. Richardson: Novartis: Employment. Isaacs: Novartis Pharmaceuticals: Employment. Melenhorst: Novartis: Research Funding. Levine: GE Healthcare: Consultancy; Tmunity Therapeutics: Equity Ownership, Research Funding; Brammer Bio: Consultancy; Novartis Pharmaceuticals Corporation: Patents & Royalties, Research Funding. June: Novartis: Patents & Royalties, Research Funding; Immune Design: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Equity Ownership, Research Funding; WIRB/Copernicus Group: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celldex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Milone: Novartis: Patents & Royalties.