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
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.