Dual specific CD19/CD22‑targeted chimeric antigen receptor T‑cell therapy for refractory diffuse large B‑cell lymphoma: A case report

Abstract

Clinical trials of chimeric antigen receptors (CARs) targeting CD19 have produced impressive results in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL). However, a notable number of patients with DLBCL fail to achieve remission after CD19 CAR T-cell therapy and may therefore require a dual targeted CAR T-cell therapy. A 31-year-old man with refractory DLBCL was assessed in the present case report. The patient was treated with sequential infusion of single CD19 CAR T cells followed by dual CD19/CD22-targeted CAR T cells. The outcome was that the patient achieved partial remission after the first single CD19 CAR T-cell infusion and complete remission after the dual CD19/CD22-targeted CAR T-cell infusion. Grade 1 cytokine release syndrome (CRS) was observed after the single CD19 CAR T-cell infusion, while grade 3 CRS and hemophagocytic syndrome were observed after the dual targeted CAR T-cell infusion, but these adverse effects alleviated after the treatments. To the best of our knowledge, the present case report is the first to describe the successful application of dual CD19/CD22-targeted CAR T-cell therapy for the treatment of refractory DLBCL. The report suggests that dual CD19/CD22-targeted CAR T-cell therapy may represent a promising option for the treatment of refractory DLBCL; however, caution should be taken due to potential CRS development.

Siglecs as Therapeutic Targets in Cancer

“…Combination therapy using CD19-and CD22-CAR-T in adult and pediatric B-ALL patients significantly enhanced the median OS (88.5% for 12 months) and progression-free survival (survival rate 67.5% for 18 months) rate and duration [226]. Similarly, dual CD19/CD22-targeted CAR T cells achieved complete remission with low-to-moderate grade treatable CRS in patients with refractory DLBCL [227].…”

Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy

“…To overcome immune escape and tumor resistance by antigen loss, bispecific CAR‐T therapy targeting multiple antigens has been evaluated. A CAR product targeting both CD19 and CD22 has been developed and demonstrated potent cytotoxic effects against leukemic blasts with promising clinical activities (Huang et al, 2020; Qin et al, 2018; Spiegel et al, 2021). A sequential CAR‐T cell infusion strategy targeting CD19 followed by CD22 has established efficacy in pilot studies and showed high MRD‐negative response rate and increased leukemia‐free survival (Pan et al, 2020; Wang et al, 2020).…”

Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications

“…Bi-specific anti-CD19/CD22 CAR T cell therapy has recently been spotlighted for its promising treatment of refractory diffuse large B cell lymphoma (DLBCL) compared to CD19 CAR T cell infusion, albeit the occurrence of CRS. 149,150 Early stages of DLBCL are usually treated with four chemotherapeutic drugs (CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]) or a combination of chemotherapy and immunotherapy (rituximab), whereas late stages undergo intense chemotherapy and allogeneic stem cell transplants. 151,152 However, some patients cannot be cured with conventional regimens and thus have to resort to CAR T cell therapy instead.…”

“…The two targets of anti-CD19/CD22 CAR T cells, CD19 and CD22, are commonly expressed on B cell lymphomas, whereas those receptors are not expressed on other cell types including hematopoietic stem cells. 150,153 By targeting those two tumor-expressed receptors, the bi-specific immunotherapeutic agent resulted in a better outcome for DLBCL patients who expressed CD19 and CD22 heterogeneously than CAR T cells that targeted CD19 only. Dual CART T cells had also expanded approximately five times greater than did CD19-specific CAR T cell in vivo.…”