CARsgen's Allogeneic BCMA CAR-T Therapy CT0596 Shows Promising Results in Rare Primary Plasma Cell Leukemia
核心洞察
CARsgen's allogeneic BCMA (搜索) CAR-T therapy CT0596 achieved stringent complete response in two heavily pretreated patients with relapsed/refractory primary plasma cell leukemia (搜索).
Both patients demonstrated robust CAR-T cell expansion with peak copy numbers exceeding 10⁵ copies/μg gDNA and achieved minimal residual disease negativity.
The therapy showed manageable safety profile with expected CAR-T-associated toxicities including cytokine release syndrome and hematologic adverse events.
CARsgen Therapeutics (搜索) has reported preliminary clinical data showing that its allogeneic BCMA (搜索)-targeted CAR-T therapy CT0596 achieved stringent complete response in two patients with relapsed/refractory primary plasma cell leukemia (搜索) (pPCL), a rare and highly aggressive malignancy with extremely limited treatment options.
Clinical Results in Heavily Pretreated Patients
As of the October 17, 2025 data cutoff, two patients with relapsed/refractory pPCL had been enrolled in investigator-initiated trials. Both patients had previously failed multiple lines of therapy including triple classes of drugs consisting of proteasome inhibitors, immunomodulatory agents, and CD38 (搜索) monoclonal antibodies.
The first patient, a 62-year-old male with IgG-λ type pPCL, had experienced poor disease control and rapid progression despite previous autologous hematopoietic stem cell transplantation. His serum free light chain level had reached 10,374.86 mg/L by the screening period. After receiving two CAR-T cell infusions approximately two months apart, the patient achieved stringent complete response at both Week 4 and Week 8 assessments, with bone marrow minimal residual disease negativity (< 10⁻⁶) at Week 4.
The second patient, a 70-year-old male with κ light chain pPCL, achieved stringent complete response at Week 4, Week 8, and Week 12 assessments post-infusion, with bone marrow MRD negativity at both Week 4 and Week 12.
Robust CAR-T Cell Expansion and Safety Profile
Both patients demonstrated robust CAR-T cell expansion, with peak copy numbers (Cmax) of 161,971 copies/μg gDNA and 151,654 copies/μg gDNA respectively, both exceeding 10⁵ copies/μg gDNA. In the first patient, CAR-T cell copy numbers remained at 10³ by Week 8.
The safety profile was characterized by expected CAR-T-associated toxicities. The first patient developed Grade 2 cytokine release syndrome (CRS), Grade 4 cytopenia, and a lung infection, but recovered after supportive treatment including tocilizumab, corticosteroids, autologous stem cell infusion, and anti-infective therapy. The second patient experienced Grade 1 CRS, Grade 4 neutropenia, and thrombocytopenia, which resolved after treatment with tocilizumab and other supportive measures. No significant organ toxicities were observed in either patient.
Addressing Critical Unmet Medical Need
Primary plasma cell leukemia (搜索) is a rare and highly aggressive plasma cell malignancy often associated with complex genetic abnormalities. Currently, there are no standard treatment regimens, and conventional therapies for multiple myeloma (搜索) are typically used. While targeted agents and autologous hematopoietic stem cell transplantation can slightly extend overall survival of pPCL patients to 1.5–3 years, relapsed/refractory pPCL after multiple lines of therapy presents a significant clinical challenge due to extremely limited treatment options and rapid disease progression.
Development Platform and Future Plans
CT0596 is developed using CARsgen's proprietary THANK-u Plus™ platform and is currently being evaluated in investigator-initiated trials for relapsed/refractory multiple myeloma (搜索) or plasma cell leukemia. The therapy demonstrated preliminary favorable tolerability and encouraging efficacy signals in these heavily pretreated patients with rapidly progressive disease.
CARsgen anticipates submitting an Investigational New Drug (IND) application in the second half of 2025. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The company has established end-to-end capabilities for CAR T-cell research and development covering target discovery, preclinical research, product clinical development, and commercial-scale production.