From the Guidelines
After blinatumomab treatment, a washout period of at least 2 weeks is recommended before collecting T cells for CAR-T cell manufacturing. This recommendation is based on the potential interference of blinatumomab with T cell collection and CAR-T manufacturing processes, as it binds to CD3 on T cells and CD19 on B cells 1. The presence of blinatumomab during leukapheresis could reduce T cell yield, impair T cell functionality, and compromise the quality of the final CAR-T product. Although the half-life of blinatumomab is approximately 2 hours, its effects on T cells can persist longer. Some centers may recommend longer washout periods of 3-4 weeks to ensure complete clearance of the drug and recovery of T cell populations. Prior to collection, a complete blood count with differential should be performed to confirm adequate lymphocyte recovery. If urgent CAR-T therapy is needed and waiting is not feasible, discussion with the cell processing laboratory is essential to determine if collection can proceed earlier, though this may result in suboptimal cell product.
The recent study by the ESMO clinical practice guideline interim update on the use of targeted therapy in acute lymphoblastic leukaemia supports the consideration of sequencing of immune therapies in r/r B-ALL, including the potential impact of prior blinatumomab use on CAR-T outcomes 1. Additionally, emerging data suggest that prior INO therapy may confer inferior CAR-T outcomes, highlighting the importance of careful consideration of treatment sequencing 1. The studies summarized in Table 3 of the ESMO guideline update provide further insight into the outcomes of CD19 CAR-T therapy for adult patients with B-ALL, including the impact of prior blinatumomab use 1. However, the most recent and highest quality study, as reported in the ESMO guideline update, supports the recommendation for a washout period after blinatumomab treatment 1.
Key considerations for T cell collection after blinatumomab treatment include:
- Washout period of at least 2 weeks
- Potential for longer washout periods of 3-4 weeks
- Complete blood count with differential to confirm adequate lymphocyte recovery
- Discussion with the cell processing laboratory for urgent CAR-T therapy
- Consideration of sequencing of immune therapies in r/r B-ALL, including prior blinatumomab use.
From the Research
Washout Car T Cell Collection After Blinatumomab
- The administration of blinatumomab prior to CAR-T cell therapy is controversial due to the potential loss of CD19+ target cells, which may negatively impact the efficacy of CAR-T cells 2.
- However, studies have shown that blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics, making it a valid option for patients with high-disease burden prior to CAR-T cell therapy 2, 3.
- In one study, 18 patients underwent blinatumomab bridging followed by CAR-T cell therapy, and 16 patients achieved complete remission after blinatumomab immunotherapy, with a complete remission rate of 88.9% 3.
- The minimal residual disease (MRD) negativity rate was higher in the blinatumomab bridging group compared to the non-bridging therapy group (94.4% vs. 61.1%) 3.
- Another study found that incorporating immune-therapies, such as chimeric antigen receptor (CAR)-T cell therapy, with or without hematopoietic stem cell transplantation (HSCT), into the treatment regimens might further improve outcomes for patients with B-cell acute lymphoblastic leukemia (B-ALL) 4.
- Blinatumomab has been shown to be effective in treating relapsed B-cell Acute Lymphoblastic Leukaemia (B-ALL) and B-cell Non-Hodgkin's Lymphoma, including in patients who are refractory to chemotherapy 5.
- A prediction model has been established to predict viral infection after CAR-T therapy in patients with relapsed/refractory B-cell malignancies, which may help identify patients at high risk of viral infection 6.