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132 Two-Year Follow-up of Investigator-Initiated Phase 1 Trials of the Safety and Efficacy of Fully Human Anti-Bcma CAR T Cells (CT053) in Relapsed/Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: CAR T Therapies for Myeloma: Novel Approaches and Longer-Term Follow Up Data
Hematology Disease Topics & Pathways:
multiple myeloma, Biological, Diseases, Therapies, CAR-Ts, Plasma Cell Disorders, Lymphoid Malignancies, Clinically relevant
Saturday, December 5, 2020: 10:15 AM

Siguo Hao, MD, PhD1*, Jie Jin, MD, PhD2, Songfu Jiang, MD3*, Zonghai Li, MD, PhD4*, Wenhao Zhang, MD, PhD1*, Min Yang, MD, PhD5*, Kang Yu, MD3*, Wei Wang, MD, PhD4*, Linjun Chen, MD, PhD1*, Haitao Meng, MD, PhD5*, Mingxia He, MD3*, Jun Xiao, MD4*, Rong Tao, MD, PhD1*, Xin Huang, MD, PhD5*, Chongyun Xing, MD3*, Daijing Yuan, MD4*, Jianbo Wan, MD, PhD1*, Shasha Wang, MD, PhD5*, Lihui Dai, BS3* and Hong Ma, MD6

1Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
2Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China
3The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
4CARsgen Therapeutics Co. Ltd, Shanghai, China
5The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
6CARsgen Therapeutics Corporation, Bellaire, TX

Background: B cell maturation antigen (BCMA) is a potential therapeutic target in multiple myeloma. CT053 comprises autologous T cells transduced with a second-generation chimeric antigen receptor (CAR) utilizing a fully human BCMA-specific single-chain fragment variant (25C2) with high binding affinity. CT053 was firstly studied in a single-arm, open-label Phase I, investigator-initiated program (NCT03716856, NCT03302403, and NCT03380039) in eastern China. Here we present the 24-month follow-up results of the study.

Methods: The multicenter exploratory Phase 1 studies included adult subjects with relapsed/ refractory multiple myeloma (RRMM) who had received at least 2 prior lines of myeloma treatment. After preconditioning treatment with fludarabine and cyclophosphamide for 2-4 days, 21 subjects received one cycle of 1.5 × 108 T cells CT053 CAR-BCMA T cells. Three subjects respectively received 0.5 × 108, 1 × 108, or 1.8 × 108 cells. The primary objective was subject safety. The secondary objectives were pharmacokinetics and efficacy. Efficacy was assessed according to IMWG 2016 criteria.

Results: A total of 24 subjects with a median age of 60.1 years (range, 38.5-69.9) were enrolled from Sept. 10, 2017 to Sept. 22, 2018. The subjects had a median of 4.5 (range, 2-11) prior lines of therapy, and 41.7% (10/24) underwent autologous stem cell transplantation. At baseline, 10 subjects (41.7%) had concomitant extramedullary involvement, 8 subjects (33.3%) had ECOG scores 2-3, and 9 subjects (37.5%) reported ISS Grade III.

As of June 30, 2020, 9 subjects completed 24 months of follow-up with responses including 8 stringent complete response (sCR) and 1 complete response (CR). Also, 15 subjects discontinued prior to completing the 24-month follow-up, of whom 13 discontinued due to disease progression (PD), and 2 discontinued for other anticancer therapy. The overall response rate was 87.5% (21/24) including 79.2% (19/24) with complete responses or stringent complete responses (3 CR, 16 sCR). The median duration of response (DOR) was 21.8 months (95%CI: 9.2, not evaluable [NE]). The median progression-free survival (PFS) was 18.8 months (95%CI: 10.1, NE), with 6-month and 12-month PFS rates of 87% and 60.9%, respectively.

Thirteen subjects progressed with median PFS of 10.2 months (range, 0.9-23 months): 3 progressed within 6 months, 6 progressed within 6-12 months, and 4 within 12-24 months. Compared to 9 subjects with persistent CR/sCR, the 13 progressed subjects had a higher percentage of ECOG scores 2-3 (46.2% vs 22.2%), ISS Grade III (53.9% vs 11.1%) and high-risk cytogenetics profiles (53.8% vs 33.3%). Rates of concomitant extramedullary diseases were similar, 46.2% and 44.4%, respectively.

Hematological toxicities were the most common treatment-related adverse events of grade (G) 3 or higher, including leukopenia (83.3%), neutropenia (85%), lymphocytopenia (79.2%) and thrombocytopenia (20.8%). In general, cytokine release syndrome (CRS) occurred at 1-4 days and resolved in a median 6 days (range, 3–9 days). Low-grade CRS was reported in 15 of 24 (62.5%) subjects. All CRS events (4 G1, 11 G2) resolved within 2-8 days; among them, 9 patients received a low dose of tocilizumab 4–6 mg/kg. One patient experienced G3 neurotoxicity, presenting as epilepsy and accompanied by simultaneous G2 CRS. This patient fully recovered within 3 days after treatment with methylprednisolone, diazepam and sodium valproate.

Six patients (25%) experienced 10 cases of treatment-related serious adverse events (SAEs), including lung infection (3), gastroenteritis (1), neutropenic infection (1), fever (1) and hematological toxicities (4). By the cutoff date, one subject died of SAE a (bone morrow failure and neutropenic infection) and PD, and seven subjects died of PD.

CAR-BCMA T cell expansion was detectable as early as day 1-7 after infusion and reached peak values on day 7-21 with the highest concentration at 4.5×105 copies/µg genomic DNA. Median T cell persistence was 172 days. The longest persistence of CAR-BCMA copies was measured at 341 days and continues. No immunogenicity was detected.

Conclusion: These studies demonstrated that CT053 had excellent efficacy in RRMM, showing early, deep and durable response with 21.8 months DOR. CT053 was well tolerated among the subjects.

Disclosures: Li: CARsgen Therapeutics Co. LtD: Current Employment, Current equity holder in private company. Wang: CARsgen Therapeutics Corp.: Current Employment. Xiao: CARsgen Therapeutics Corp.: Current Employment. Yuan: CARsgen Therapeutics Corp.: Current Employment. Ma: CARsgen Therapeutics Corp.: Current Employment.

*signifies non-member of ASH