How does CAR-T for LBCL work?

There are three types of CAR T-cell therapy approved for LBCL in the United States. These include: 

• Axi-cel (Yescarta)
• Liso-cel (Breyanzi)
• Tisa-cel (Kymriah)

All three enhance your T cells to target CD19 on LBCL cells. Learn more at: How CAR T-cell Therapy Works.  

Which LBCL patients can receive CAR-T? 

People with relapsed or refractory LBCL are eligible for the different CAR-T constructs in the following situations: 

• Axi-cel: Adult patients with LBCL are eligible if either:
  • They were refractory to first-line chemoimmunotherapy or relapsed within 12 months of first-line chemoimmunotherapy.
  • They relapsed or were refractory after 2 or more lines of systemic therapy.
• Liso-cel:
  • Patients with LBCL are eligible if they have either:
    • Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
    • Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy, and are not eligible for a stem cell transplant due to co-existing health issues or age.
    • Relapsed or refractory disease after 2 or more lines of systemic therapy.
• Tisa-cel:
  • Adult patients with relapsed or refractory LBCL after 2 or more lines of systemic therapy. 

To learn about more factors that may influence whether CAR-T is right for you, visit: When to Consider CAR T-cell Therapy?

When will my CAR-T infusion for LBCL be ready? 

The CAR-T process takes time. Since collecting your T-cells, it takes up to 4 weeks for the CAR-T infusion to be ready. 

During this waiting period, your doctor may recommend a temporary bridging therapy like corticosteroids or radiotherapy to help keep LBCL under control until your CAR-T infusion. 

How is CAR T-cell therapy administered for LBCL?

Before your CAR-T infusion, you will receive a short course of chemotherapy with cyclophosphamide and fludarabine through an IV daily for 3 days. This step is called lymphodepletion, and it helps prepare your body so CAR-T works more effectively. Your CAR-T infusion is typically given 2 to 4 days after this chemotherapy. If you experience serious side effects from lymphodepletion, active infections, or inflammatory disorders, the CAR-T infusion may be delayed until these side effects are resolved. 

About 30 to 60 minutes before the CAR-T infusion, you will be given acetaminophen and diphenhydramine by your healthcare team to help lower the risk of side effects. The CAR-T infusion itself takes between 30 and 60 minutes.  

Afterward, you will be monitored closely for at least 7 days. This is to watch for possible side effects such as cytokine release syndrome (CRS) and neurological changes. You will also need to stay near the treatment center and avoid driving for at least 2 weeks after the infusion. The requirements used to be longer but were recently updated based on the FDA’s removal of the Risk Evaluation and Mitigation Strategies (REMS). 

Axi-cel (Yescarta) for LBCL

How effective is axi-cel for LBCL?

For people with LBCL whose first treatment with chemoimmunotherapy didn’t work—either because the lymphoma didn’t respond or came back within a year—and who were eligible for an autologous stem cell transplant, the ZUMA-7 trial looked at how well treatment with axi-cel worked. The results showed that 65% of participants experienced a complete remission, which lasted for a median of 28.4 months. There were 18% of patients who experienced a partial remission, which lasted for a median of 1.6 months. 

Side effect profile of axi-cel for LBCL

The lists below show the percentage of people with LBCL who experienced the 5 most common and severe side effects from axi-cel in the ZUMA-7 trial. This information can help you understand what to expect and prepare for, as well as guide conversations with your care team about managing potential side effects. 

The 5 most common side effects (any grade) that LBCL patients experienced after receiving axi-cel were: 

• Fever: 93%  
• Cytokine release syndrome: 92% 
• Infections: 60%
• Fatigue: 52% 
• Hypotension (low blood pressure): 47%

The 5 most severe side effects in which patients required supportive hospital care (grades 3 and higher), apart from low blood counts, included: 

• Febrile neutropenia (fever from low neutrophils): 31% 
• Encephalopathy (a group of conditions that cause brain dysfunction): 18% 
• Infections: 18% 
• Hypotension (low blood pressure): 11% 
• Hypoxia (low levels of oxygen in body tissues): 9% 

For more information on axi-cel for LBCL, check out the source below. 

• Yescarta Prescribing Information

For information on how to manage CAR-T side effects, visit: Side Effect Management of CAR T-cell Therapy for Lymphoma.

Liso-cel (Breyanzi) for LBCL 

How effective is liso-cel for LBCL? 

For people with LBCL whose first treatment with chemoimmunotherapy didn’t work—either because the lymphoma didn’t respond or came back within a year—and who were eligible for an autologous stem cell transplant, the TRANSFORM study looked at how well treatment with liso-cel worked. The results showed that 74% of participants experienced a complete remission and 13% a partial remission. After 24 months, 60.5% of these patients remained in remission. 

Side effect profile of liso-cel for LBCL 

The lists below show the percentage of LBCL patients in the TRANSFORM trial who experienced the 5 most common and severe side effects from liso-cel. This information can help you understand what to expect and prepare for, as well as guide conversations with your care team about managing potential side effects. 

The 5 most common side effects (any grade) that LBCL patients experienced after receiving liso-cel were: 

• Fever: 55% 
• Cytokine release syndrome: 49%
• Musculoskeletal pain: 36%
• Headache: 34%
• Fatigue: 28%

The 5 most severe side effects in which patients required supportive hospital care (grades 3 and higher), apart from low blood counts, included: 

• Infections: 19%
• Febrile neutropenia: 10% 
• Headache: 6%
• Fever: 3.4%
• Musculoskeletal pain: 3.4%

To learn more about liso-cel for LBCL, including how well it worked as a third treatment option, see the source below. 

• Breyanzi Prescribing Information

For information on how to manage CAR-T side effects, visit: Side Effect Management of CAR T-cell Therapy for Lymphoma. 

Tisa-cel (Kymriah) for LBCL 

How effective is tisa-cel for LBCL? 

Results from the JULIET study, which tested tisa-cel as a third treatment for people with relapsed or refractory LBCL, showed that 39% of participants experienced a complete remission and 14% a partial remission. After a median of 40.3 months, 60% of these patients remained in remission. However, the disease response rates with tisa-cel were not better than those for patients treated with stem cell transplants. That is why tisa-cel is only approved for the treatment of LBCL after two or more types of treatment of lymphoma. 

Side effect profile of tisa-cel for LBCL 

The data below shows the percentage of people with LBCL who experienced the 5 most common and severe side effects from tisa-cel in the JULIET study. This information can help you understand what to expect and prepare for, as well as guide conversations with your care team about managing potential side effects. 

The 5 most common side effects (any grade) that LBCL patients experienced after receiving tisa-cel were: 

• Infections: 87% 
• Cytokine release syndrome: 74%
• Fever: 35%
• Diarrhea: 31%
• Nausea: 29% 

The 5 most severe side effects in which patients required supportive hospital care (grades 3 and higher), apart from low blood counts, included: 

• Infections: 41%
• Cytokine release syndrome: 23%
• Febrile neutropenia (fever from low neutrophils): 17% 
• Encephalopathy (a group of conditions that cause brain dysfunction): 11%
• Hypotension (low blood pressure): 9%

For more information on tisa-cel for LBCL, check out the source below. 

• Kymriah Prescribing Information

For information on how to manage CAR-T side effects, visit: Side Effect Management of CAR T-cell Therapy for Lymphoma.

Financial resources for LBCL CAR-T

To locate financial resources for LBCL CAR T-cell therapies like axi-cel, liso-cel, and tisa-cel, visit: Financial Resources for Lymphoma CAR-T.