New CAR-T Therapy CT0596 Shows Promise for Treating Primary Plasma Cell Leukemia

CARsgen's Allogeneic BCMA CAR-T Therapy CT0596 in Clinical Trials for Primary Plasma Cell Leukemia

On October 19, 2025, CARsgen Therapeutics announced preliminary data for their innovative CAR-T therapy, CT0596, specifically targeting primary plasma cell leukemia (pPCL). This malignancy is rare but highly aggressive, presenting significant treatment challenges due to the lack of standardized protocols. Traditional therapies for multiple myeloma are often employed; however, their effectiveness is limited with median survival rates for pPCL patients remaining between 1.5 to 3 years post-treatment.

Understanding Primary Plasma Cell Leukemia

Primary plasma cell leukemia is characterized by abnormal plasma cells in the bloodstream, leading to severe complications and requiring immediate and effective treatment solutions. Many patients undergo multiple treatment lines before facing either relapse or refractory disease, making new therapeutic options critical.

CT0596, developed using CARsgen's proprietary THANK-u Plus™ platform, aims to address these needs by targeting BCMA (B-cell maturation antigen), which is prevalent in pPCL. In the current clinical evaluation, two patients with relapsed/refractory pPCL were enrolled, showcasing the therapy's potential in this challenging context.

Patient Profiles and Treatment Response

The first patient, a 62-year-old male, had previously received an autologous stem cell transplant alongside various drug therapies but showed poor disease control. After two CAR-T cell infusions, significant clinical improvements were observed, including a peak CAR-T cell count of 161,971 copies per microgram of genomic DNA and a stringent complete response (sCR) within four weeks of the second infusion. Notably, this patient experienced manageable side effects, including Grade 2 cytokine release syndrome (CRS).

The second patient, a 70-year-old male, also showed encouraging results after treatment with CT0596, achieving sCR at several checkpoints throughout his post-infusion assessments. His peak CAR-T count reached 151,654 copies per microgram of gDNA, supporting the therapy's efficacy and safety as evidenced by the resolution of complications with standard supportive care.

Safety and Efficacy Insights

Across both patient cases, CT0596 displayed rapid and robust efficacy, even following extensive pre-treatment. Patients achieved sCR with negative minimal residual disease (MRD) status at various points, with no severe organ toxicities reported, which underscores the therapy's favorable safety profile. The successful outcomes present a compelling case for the continued evaluation of CT0596 in broader studies targeting various plasma cell neoplasms.

Future Directions for CARsgen

As a frontrunner in CAR-T cell therapy, CARsgen is set to bolster its clinical portfolio, planning to submit an Investigational New Drug (IND) application by the latter half of 2025. With a focus on leveraging innovative CAR T-cell technologies, the firm's mission is to expand treatment possibilities for patients with unmet medical needs across hematologic malignancies and autoimmune diseases.

By advancing therapies like CT0596, CARsgen aims to redefine outcomes for patients suffering from aggressive leukemias and malignancies, establishing themselves as a leader in transformative biopharmaceutical solutions. As the study progresses, further insights are anticipated, marking a significant leap in the fight against complex cancers.