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
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.
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