Study of Targeted CD22/CD19 CAR-T Therapy for First-line Consolidation of B-cell Lymphoma

Only a portion of patients with invasive B-cell lymphoma can achieve complete response through standard combination therapy with R-CHOP, and a considerable number of patients have poor prognosis and face treatment difficulties such as drug resistance and recurrence. In the previous guidelines of the National Comprehensive Cancer Network (NCCN) in the United States, high-risk diffuse large B-cell lymphoma (defined as stage III-IV, or stage I-II with extensive mesenteric involvement) patients showed complete response after completing six cycles of first-line induction therapy. Subsequently, autologous stem cell transplantation (ASCT) and involved site radiation therapy (ISRT) can be used for consolidation treatment. However, the SWOG 9704 study found that patients with medium to high risk/high-risk B-cell lymphoma who achieved at least partial response to first-line treatment and received ASCT consolidation therapy did not benefit from ASCT in terms of progression free survival/overall survival in the medium to high risk group, only in terms of overall survival and disease-free survival in the high-risk group. In addition, the DLCL04 study showed that medium to high-risk or high-risk patients with an Age Adjusted International Prognostic Index (aaIPI) score of 2-3 who achieved complete or partial response to first-line treatment did not benefit from ASCT. In the 2024 NCCN guidelines for diffuse large B-cell lymphoma, first-line consolidation therapy for high-risk diffuse large B-cell lymphoma patients after induction therapy only includes close follow-up and radiation consolidation therapy for the affected areas of the original mass and bone lesions. There is no more aggressive treatment strategy to positively address the relatively high risk of disease recurrence and progression in this group of high-risk patients. CAR-T cell immunotherapy has achieved good clinical therapeutic effects in hematological tumors. After induction therapy, first-line CAR-T cell immunotherapy consolidation therapy is expected to improve the disease prognosis of high-risk invasive B-cell lymphoma patients and bring long-term survival benefits. Compared to CAR-T cell immunotherapy, which can directly control adverse reactions with immunosuppressive drugs such as glucocorticoids, the risk of autologous hematopoietic stem cell transplantation is higher, and patients have a greater risk of non recurrent mortality (NRM) due to complications such as infection and bleeding. The latest version of the NCCN guidelines for diffuse large B-cell lymphoma no longer recommends autologous hematopoietic stem cell transplantation as the first-line consolidation treatment for high-risk diffuse large B-cell lymphoma. Therefore, new first-line consolidation treatment plans after induction therapy are still needed to further improve the survival prognosis of high-risk invasive B-cell lymphoma patients. Based on the many difficulties that still exist in the first-line standard treatment plan for high-risk invasive B-cell lymphoma patients, this study plans to explore the effectiveness and safety of CD22/CD19 CAR-T cell immunotherapy as first-line consolidation therapy for high-risk invasive B-cell lymphoma patients after standard first-line induction therapy, in order to improve the prognosis of such patients and provide new treatment options for first-line consolidation therapy of high-risk invasive B-cell lymphoma.