Abstract
<title>Abstract</title> <p> <bold>Background:</bold> Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is defined as a malignant clonal proliferation of lymphocytes originating in the skin. It is highly invasive, often occurs in the elderly, has a poor prognosis, and has a high recurrence rate. Although the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable therapeutic effects in patients with relapsed/refractory (R/R) B-cell lymphoma, data regarding its application in R/R PCDLBCL-LT remain limited. Further clinical research is needed to establish its efficacy in this specific subtype. <bold>Patients and methods:</bold> A <bold/> retrospective single-center cohort study with over 3-year follow-up enrolled in seven patients with R/R PCDLBCL-LT who received CD19 CAR-T celltherapy in our hospital. The follow-up period for all patients after CAR-T cell infusion was more than 3 years. We observed the overall response rate (ORR), the expression of CAR-T cell amplification, cytokines, the adverse events and the local cytokine release syndrome (CRS). Patients who obtained ORR received maintenance treatment after CAR-T cell therapy (PD-1 inhibitors-based maintenance treatment or allo/auto-HSCT). <bold>Results:</bold> The ORR was 71.42% (5/7), with a progression-free survival (PFS) rate of 28.57% (2/7) and an overall survival (OS) rate of 42.86% (3/7). Among the seven patients, four achieved a complete response (CR) and one achieved a partial response (PR) two months after CAR-T cell infusion. However, only three patients had maintained CR for more than 3 years post-infusion. The peak expansion of CD19 CAR-T cells occurred between days 4 and 7 after infusion in all patients except Pt 2, whose peak occurred on day 30. No statistical correlation was observed between clinical response, the grade of CRS/ICANS, hematological toxicity, and either the peak CAR-T cell level or peak IL-6 level. Pt 2, who had a high tumor burden and achieved CR, experienced local CRS on day 30 post-infusion. <bold>Conclusions:</bold> During a >3-year follow-up, R/R PCDLBCL-LT patients achieving ORR from CAR-T therapy still faced recurrence and death risks. Post-CAR-T maintenance warrants exploration. No link was found between response/toxicity and CAR-T peaks or IL-6 levels. However, local CRS in high tumor burden patients warrants close monitoring. <bold>Trial registration:</bold> <italic>ChiCTR1800019622. The project was registered on November 21, 2018. It was originally scheduled for completion on November 14, 2021, but was ultimately completed in June 2023, because of the COVID-19 pandemic, https://www.chictr.org.cn/showproj.html?proj=33185.</italic> </p>