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3447 Long-Term Remission and Survival in Patients with Rituximab-Refractory/Relapsed B-Cell Non-Hodgkin Lymphoma after Treatment with U16 (CD20 CAR-T cells)

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Qian Cheng1*, JingWen Tan2*, Rui Liu1*, Liqing Kang2*, Hongjia Zhu2*, Yi Zhang1*, Erhua Wang1*, Ying Li, MD1*, Jian Zhang1*, Han Xiao3*, Rong He, MD4, Xiaoyan Lou2*, Nan Xu2*, Wei Wang2*, Zhou Yu2*, Minghao Li2*, Hongfei Gu5*, Lei Yu2* and Xin Li1*

1Department of Hematology, Third Xiangya Hospital of Central South University, Changsha, China
2Shanghai Unicar-Therapy Bio-Medicine Technology Co.,Ltd, Shanghai, China
3Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, China
4Division of Hematopathology, Mayo Clinic, Rochester, MN
5Hongmian Cancers and Rare Disorders Charity Foundation of Guangzhou, Guangzhou, China

Background: Rituximab is a monoclonal antibody that targets CD20 and can significantly improve the prognosis of patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). Nonetheless, a significant number of patients experience disease progression or relapse post-rituximab therapy. CD19-chimeric antigen receptor (CAR) T cells have demonstrated remarkable efficacy in B-NHL treatment. However, few studies have focused on the efficacy and safety of CD20 CAR-T cells in rituximab-refractory/relapsed (R/R) B-NHL patients, particularly those treated with rituximab for a short time.

Here, we conducted a prospective study, aimed to assess the long-term remission and survival in patients with rituximab-R/R B-NHL after treatment with U16 (CD20 CAR-T cells).

Methods: This first-in-human study is an open-label, single center investigator-initiated trial (IIT) to determine the safety and efficacy of CD20 CAR-T in R/R B-NHL after previous rituximab treatment failure (no. ChiCTR2000036350). CD20 CAR-T was administered at a target dose of 1.0×107 CAR-T cells/kg after a 3-day conditioning chemotherapy with fludarabine and cyclophosphamide. The primary objective was to assess the safety and tolerability of CD20 CAR-T. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded according to ASTCT 2019 criteria. The secondary objectives were to evaluate efficacy and pharmacokinetics (PK). Response was assessed per Lugano 2014 criteria.

Results: A total of 16 patients with R/R B-NHL were enrolled.The median age was 49 years (range, 28-66). Median number of prior lines of therapy was 3 (range, 2-5). All patients had received rituximab therapy; of these, 9 had done so within the 3 months before CAR-T infusion.

CRS occurred in all patients, with 11 patients (68.75%) experiencing grade 1 or 2 CRS and 5 patients (31.25%) experiencing grade 3 CRS. No patient developed grade 4 CRS , and only one patient had ICANS.The most common grade 3 or higher adverse events observed after infusion included leukopenia (93.3%), anemia (40%) and thrombocytopenia (60%).

An overall response rate of 100% was observed among enrolled patients, with 11 patients (68.75%) achieving complete remission(CR) and 5 patients (32.25%) achieving partial remission(PR) within 3 months.

The median follow-up time was 11.7 months(range 0.69-47.47). The median overall survival was not reached, and the median progression-free survival was 14.5 months. 9 patients remained CR or PR for 12 months, with 7 of them continuing in CR for up to 24 months.

The pharmacokinetics of CD20 CAR-T cells were assessed using quantitative PCR to determine the expansion and persistence ability. Peak CAR amplification were detected 7-14 days after infusin. Patients 1, 2 and 4 achieved long-term remission, and persistent positive CAR-T cell copy numbers were detected for 15 months, 30 months and 26 months, respectively. However, patients 7, 8 and 12 relapsed within 3 months, and the CAR-T cell copies of all three patients were reduced to fewer than 1×103 copies/μg of DNA within 3 months. The qPCR results indicated that the maintenance of efficacy was closely related to the persistence of CAR-T cells.

Notably, patients who received rituximab less than 3 months before CAR-T infusion had a poorer prognosis, with higher relapse rates (77.8% vs. 28.6%) and shorter progression-free survival, regardless of the degree of response.

Conclusion: Long-term follow-up demonstrated that CD20 CAR-T therapy can produce a deep and durable response with a favorable safety profile in patients with rituximab-refractory/relapsed B-NHL. Notably, patients who had received rituximab within 3 months had a poorer prognosis.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH