Combination Anti-Bcma and Anti-CD19 CAR T Cells As Consolidation of Response to Prior Therapy in Multiple Myeloma

BACKGROUND Anti-BCMA CAR T cells are effective in relapsed/refractory multiple myeloma (RRMM), but most patients eventually progress. Extensive prior therapy and high disease burden in RRMM pts may compromise CAR T cell safety, feasibility, and efficacy, and rare BCMA-neg/CD19+ MM cells with enhanced clonogenic potential may mediate relapse after anti-BCMA CARs. We therefore initiated a trial of anti-BCMA CAR T cells (CART-BCMA) as consolidation of response to prior MM therapy, including high-risk (HR) pts responding to first-line therapy, and combined CART-BCMA with anti-CD19 CAR T cells (CTL119). Both CART-BCMA and CTL119 are 4-1BB/CD3z-based CARs transduced via lentiviral vector. CART-BCMA was previously reported (Cohen et al JCI 2019) and exhibited 64% response rate at 5x108 cell dose following cyclophosphamide (cy) alone as lymphodepleting chemo in RRMM. CTL119 is a humanized version of tisagenlecleucel. METHODS To assess safety/feasibility of CART-BCMA + CTL119, Phase A (PhA) is evaluating the combination in pts responding (≥MR) to ≥3rd line therapy (or ≥2nd line if exposed to all major agents). After early PhA results showed no excessive toxicity, Phase B (PhB) began enrolling HR pts (R-ISS 3, complex karyotype, PC leukemia, or RESULTS 6/7 enrolled PhA pts were infused; 1 pt died due to CNS progression before infusion. 4/4 enrolled PhB pts were infused (2 CART-BCMA alone, 2 CART-BCMA + CTL119). See table for age & prior # therapies; 9/10 had HR cytogenetics or were R-ISS 3. Regarding mfg feasibility, 2 PhA pts (05, 07) failed to meet full target doses; all 4 PhB pts achieved full dose. Two subjects (01, 03) had the 3rd (60%) dose held due to early fevers. CRS was gr 0-2 by ASTCT criteria and was observed in pts with both high and low disease burden (table). No neurologic toxicity was observed. Gr 3-4 toxicities were mainly hematologic; 3/6 PhA pts had either ANC CONCLUSIONS Preliminary results support safety and high initial response-rate of CART-BCMA + CTL119 after cy/flu in MM. In pts with low disease burden responding to prior therapy, including first-line therapy, CAR T cells expanded in vivo and generated clinical responses with low-grade CRS and no neurotoxicity. Preliminarily, hematologic toxicity and feasibility of maint seem more favorable in first-line setting. Addition of CTL119 did not clearly prevent progression after CART-BCMA in the PhA population (3-9 prior lines); data from PhB with randomization +/- CTL119 are immature. Accrual is ongoing, and updated results will be presented at the meeting. Download : Download high-res image (1MB) Download : Download full-size image Table . Disclosures Garfall: Surface Oncology: Consultancy; Novartis: Patents & Royalties: inventor on patents related to tisagenlecleucel (CTL019) and CART-BCMA, Research Funding; Janssen: Research Funding; Amgen: Research Funding; Tmunity: Honoraria, Research Funding. Cohen: Poseida Therapeutics, Inc.: Research Funding. Lacey: Novartis: Research Funding; Tmunity: Research Funding; Novartis: Patents & Royalties: Patents related to CAR T cell biomarkers. Tian: Novartis: Research Funding. Hwang: Novartis: Research Funding; Tmunity: Research Funding. Vogl: Active Biotech: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Lancaster: novartis: Research Funding. Nelson: Novartis: Research Funding. Ferthio: Novartis: Research Funding. Fesnak: Novartis: Research Funding. Melenhorst: National Institutes of Health: Research Funding; IASO Biotherapeutics, Co: Consultancy; Simcere of America, Inc: Consultancy; Incyte: Research Funding; Shanghai Unicar Therapy, Co: Consultancy; Colorado Clinical and Translational Sciences Institute: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding, Speakers Bureau; Stand Up to Cancer: Research Funding; Parker Institute for Cancer Immunotherapy: Research Funding; Genentech: Speakers Bureau. Young: novartis: Research Funding. Levine: Brammer Bio: Membership on an entity's Board of Directors or advisory committees; Vycellix: Membership on an entity's Board of Directors or advisory committees; Incysus: Membership on an entity's Board of Directors or advisory committees; Cure Genetics: Consultancy; Novartis: Consultancy; Novartis: Consultancy, Patents & Royalties, Research Funding; Tmunity Therapeutics: Equity Ownership; CRC Oncology: Consultancy; Avectas: Membership on an entity's Board of Directors or advisory committees. Brogdon: Novartis: Employment. Isaacs: Novartis: Employment. June: Tmunity: Other: scientific founder, for which he has founders stock but no income, Patents & Royalties; Novartis: Research Funding. Milone: Novartis: Patents & Royalties, Research Funding. Stadtmauer: Amgen: Consultancy; Novartis: Consultancy, Research Funding; Tmunity: Research Funding; Abbvie: Research Funding; Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy.