Does Treatment Order of CAR T-cell Therapy and Bispecific Antibodies Matter for LBCL?

Researchers studied whether the order in which people with large B-cell lymphoma (LBCL) receive CAR T-cell therapy and bispecific antibodies affects their outcomes. Below, read the findings of this real-world research that was presented at the 2025 American Society of Hematology (ASH) conference. 

Understanding CAR T-cell therapy and bispecific antibodies

CAR T-cell therapy uses your own immune cells to treat cancer. Your immune cells are changed in a lab to target lymphoma cells. Bispecific antibodies are medicines that connect immune cells to lymphoma cells to help the immune system remove the cancer.

Both CAR-T and bispecific antibodies are effective options for relapsed or refractory LBCL. Relapsed lymphoma has come back after treatment, and refractory means the lymphoma was not controlled by prior treatment. Researchers wanted to know whether receiving one therapy before the other changed how well each treatment works later. 

This matters because people with LBCL may need more than one treatment over time. Knowing the best order could help improve patients’ survival and quality of life. 

How treatment sequencing was studied 

Researchers reviewed real-world data from 1,031 adults with relapsed/refractory LBCL treated between 2015 and 2024. Real-world data means the information was collected from patients who received treatment outside of clinical trials. This shows how therapies work in everyday care. 

Patients were grouped based on which treatment they received first:

• Bispecific antibody after CAR-T
• Bispecific antibody without prior CAR-T
• CAR-T after a bispecific antibody
• CAR-T without a prior bispecific antibody

Researchers looked at factors like whether patients experienced remission, the number of patients who were alive without lymphoma progression, and side effects like cytokine release syndrome (CRS). 

These comparisons can help doctors understand which treatment sequence may give patients the best chance for longer remission and survival. 

Bispecific antibodies after CAR-T 

They found that people with relapsed/refractory LBCL who received bispecific antibodies after CAR-T had similar results to those who had not received CAR-T before.  Complete remission rates, progression-free survival, overall survival, and side effects were similar. 

For patients with a high-risk subtype called double-hit lymphoma, responses to bispecific antibodies lasted longer if CAR-T had not been given first. 

These findings show that bispecific antibodies may still work even if CAR-T has already been used, giving patients another option later. 

CAR-T after bispecific antibodies 

CAR-T outcomes were also similar whether or not patients previously received bispecific antibodies. The percentage of patients who were in remission, the amount of time remission lasted, and side effect rates were alike. 

However, for patients whose lymphoma did not respond to their first treatment, survival rates were better when CAR-T was used before bispecific antibodies. 

This highlights that starting with CAR-T may be especially important for people whose lymphoma didn’t respond to their first treatment.

What this means for treatment planning

Overall, the order of CAR-T and bispecific antibodies did not strongly change outcomes for most patients. But, there were two important patterns:

• CAR-T may be best used first when possible because it can potentially lead to long-term remission
• Bispecific antibodies still work well even after CAR-T

Talking with your care team about treatment sequencing may help you plan for both current and future therapy options. 

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Source: 

• Impact of sequencing of CART vs bi-specific antibody on survival in relapsed/refractory large B-cell lymphoma: An analysis from the ABC consortium