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Abstract Introduction: The current treatment of R/R AML and BPDCN is associated with poor outcome. CD123 is overexpressed on AML blasts, leukemic stem cells, and BPDCN cells compared to normal hematopoietic stem cells. This differential expression feature makes CD123 an attractive target for cellular immunotherapy. Here we report results of an ongoing single-center, first-in-human phase 1 dose-escalation study (NCT02159495) evaluating CD123CAR T cells in treating patients with R/R AML (cohort 1) and BPDCN (cohort 2). This study is designed to determine the safety and antileukemic activity of CD123CAR T cells. Methods: Vectors containing the CD123CAR composed of a single-chain variable fragment, an optimized IgG4 linker, a CD28 co-stimulatory domain, and a CD3 zeta domain are used to engineer donor-derived or autologous T cells via lentiviral transduction. Prior to T-cell infusion, all patients undergo lymphodepleting regimen with the majority receiving fludarabine 25-30 mg/m2 and cyclophosphamide 300-500 mg/m2 daily for 3 days. Patients can receive a second infusion if they continue to meet eligibility criteria. To date, 18 patients have been enrolled and 9 treated (7 AML, 2 BPDCN). Results: All 7 patients in the AML cohort had at least one prior allogeneic stem cell transplant and median of 4 (range: 4-10) prior lines of therapy. Of the 2 patients treated at the dose level (DL) 0 (50M CAR+ T), one achieved a morphologic leukemic-free state (MLFS), which lasted 70 days. She received a second infusion 3 months later with blast reduction from 77.9% to 0.9% (flow cytometry) after 35 days. Of the 5 patients on the DL1 (200M CAR+ T), 1 achieved complete remission (CR) with incomplete count recovery at day 28, and 1 MLFS that improved to CR at day 84. The remaining 3 patients had stable disease. All toxicities were reversible and manageable. No patient developed grade 3 or above cytokine release syndrome or neurotoxicity. There were no treatment-related dose-limiting toxicities and no treatment-related cytopenias longer than 12 weeks. One patient with prior cutaneous GVHD developed grade 1 rash 5 weeks after CAR T infusion, which resolved after clinical management. Peak of T-cell expansion occurred within the first 14 days. We did not observe any CD123-loss leukemic variants. In the BPDCN cohort, 2 patients treated at DL0 (100M CAR+ T) tolerated the treatment well with no grade 3 or above treatment-related toxicities. One patient achieved CR with no evidence of disease in the bone marrow and skin at day 28. Conclusions: In this first-in-human clinical trial of CD123CAR T cell therapy, we have demonstrated the feasibility, safety, and promising antileukemic activity of targeting CD123 in patients with AML or BPDCN. Based on the results we have observed and our collaborative work with Mustang Bio at optimizing the manufacturing platform, we will be leading a multicenter phase 1/2 clinical trial to determine the activity of the cells in achieving remission in patients with AML, BPDCN, and myelodysplastic syndrome. This abstract is also being presented as Poster B22. Citation Format: Lihua E. Budde, Joo Song, Marissa Del Real, Young Kim, Candida Toribio, Brent Wood, Jamie Wagner, Emanuela Marcucci, Anthony Stein, Guido Marcucci, Christine E. Brown, Stephen J. Forman. CD123CAR displays clinical activity in relapsed/refractory (r/r) acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN): Safety and efficacy results from a phase 1 study abstract. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr PR14.
Budde et al. (Wed,) studied this question.