From the Guidelines
Rituximab and CAR-T therapy have a complex relationship, with recent rituximab treatment potentially reducing the effectiveness of CD19-directed CAR-T therapy due to depletion of target B cells expressing both CD19 and CD20. The mechanism of action of rituximab, a monoclonal antibody targeting the CD20 protein on B cells, leads to their destruction through various immune mechanisms 1. In contrast, CAR-T therapy involves genetically modifying a patient's own T cells to express chimeric antigen receptors that recognize specific cancer antigens, most commonly CD19 on B cells 1. Key differences in their administration and use include:
- Rituximab is typically administered intravenously at doses of 375 mg/m² weekly for 4 weeks in many lymphoma protocols, though regimens vary by condition 1.
- CAR-T therapy, on the other hand, involves a one-time treatment after lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Considering the timing and sequence of these therapies is crucial when planning treatment for B-cell malignancies, as recent rituximab treatment may impact the efficacy of subsequent CAR-T therapy 1. Some important considerations include:
- The potential for rituximab to deplete B cells expressing both CD19 and CD20, reducing target cells for CAR-T cells 1.
- The importance of monitoring and managing potential side effects, such as infusion reactions, infectious complications, and late-onset neutropenia, associated with rituximab treatment 1. Overall, the relationship between rituximab and CAR-T therapy highlights the need for careful planning and consideration of the timing and sequence of these therapies to optimize treatment outcomes for patients with B-cell malignancies.
From the Research
Relationship between Rituximab and CAR-T cells
The relationship between Rituximab and Chimeric Antigen Receptor T cells (CAR-T) is explored in several studies, which suggest that Rituximab may improve the efficacy of CAR-T therapy in certain types of cancer.
- Improved clinical outcomes: A study published in 2024 2 found that adding Rituximab to CAR-T therapy may improve clinical outcomes in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). The study found that the 2-year overall survival and leukemia-free survival rates were higher in the Rituximab group compared to the control group.
- Sensitizing leukemia cells to CAR-T-mediated cytotoxicity: The same study 2 found that Rituximab may sensitize leukemia cells to CAR-T-mediated cytotoxicity, making them more effective at killing cancer cells.
- Reducing CAR-T exhaustion: The study also found that Rituximab may reduce CAR-T exhaustion, which can improve the long-term efficacy of CAR-T therapy.
- Successful combination therapy: Another study published in 2024 3 reported a case of a patient with diffuse large B-cell lymphoma who experienced relapse after CAR-T therapy, but achieved long-term remission after treatment with polatuzumab vedotin and Rituximab.
CAR-T cell therapy
CAR-T cell therapy is a type of immunotherapy that involves genetically engineering T cells to express a synthetic receptor that recognizes a tumor cell surface antigen. Several studies have explored the efficacy of CAR-T cell therapy in various types of cancer, including:
- Hematologic malignancies: A review published in 2024 4 found that CAR-T cell therapy has improved overall survival and progression-free survival in patients with large B-cell lymphoma and multiple myeloma.
- Pediatric acute lymphoblastic leukemia: The same review 4 found that CAR-T cell therapy has achieved durable remission in patients with pediatric acute lymphoblastic leukemia.
- Emerging therapies: A review published in 2019 5 discussed the emerging therapies in CAR-T cell therapy, including bispecific CAR, Tan-CAR, inhibitory-CAR, and combined antigens.
Targeted therapies in lymphomas
Targeted therapies, including monoclonal antibodies and small-molecule inhibitors, have expanded considerably over the last 20 years for the treatment of B-cell and T-cell lymphomas. A review published in 2019 6 summarized the current targeted therapies that have received regulatory approval for the treatment of lymphomas, including Rituximab, a monoclonal antibody directed at the CD20 lymphocyte antigen.