Can Side Effect Risk Be Predicted for LBCL CAR-T and Bispecific Antibodies?

Recent studies looked at how doctors can better predict side effects from CAR T-cell therapy and bispecific antibodies for large B-cell lymphoma (LBCL). Learn how new tools may help find who may benefit most from treatment and lower the risk of serious immune side effects. 

New “toxicity-free” outcomes show who benefits from CAR-T without severe side effects 

CAR-T results are often discussed in two separate buckets: how well it controls lymphoma and how often serious immune side effects happen. This study combined those ideas into new “composite end-points” in the first 100 days after CAR-T for people with LBCL.

Researchers defined:

• tfCR100: complete response at day 100 without severe CRS or severe ICANS

• tfPFS100: alive at day 100, no progression, and no severe CRS or severe ICANS

In 627 people, 53% experienced tfPFS100 and 38.6% experienced tfCR100. Those who achieved tfCR100 had excellent outcomes at two years.

People who had a complete response but did experience severe ICANS after treatment had a higher risk of death related to the side effect. This supports the idea that preventing and managing severe ICANS matters for long-term health. Click here to learn how ICANS is managed. 

Read this abstract: Novel composite end-points toxicity/progression-free survival (tfPFS) and toxicity-free complete remission (tfCR100) after CAR-T cell therapy for diffuse large B cell lymphoma: Cell therapy consortium analysis.

A simple scoring system may predict response and side effects with CAR-T

An Australian real-world study included 632 people with LBCL who went through apheresis, the cell collection for CAR T-cell therapy. They studied tisa-cel (Kymriah, Novartis) and axi-cel (Yescarta, Kite/Gilead), and looked for easy-to-use predictors of outcomes and severe side effects.

At apheresis, a two-factor model helped estimate risk:

• The patient’s relapsed or refractory status, meaning the lymphoma didn’t respond to or came back after the most recent therapy
• High lactate dehydrogenase (LDH), a blood marker that can rise with more active lymphoma

Before lymphodepletion, a three-factor model worked best:

• A person’s performance status, which measures how well they can perform daily activities
• Response to bridging therapy, a treatment used while waiting for CAR-T
• High LDH

People with more risk factors had lower progression-free survival and higher chances of severe CRS or ICANS. One standout point was that responding to bridging therapy was linked to better outcomes. For patients, this kind of score could help with planning, including whether to push for stronger bridging therapy, consider a clinical trial, or choose a different sequencing strategy. 

Read this abstract: A simple scoring system for response and toxicity following lymphoma CAR-T: Results from the Australian CAR-T real-world consortium 

Who is more likely to develop CRS or ICANS with bispecific antibodies?

Bispecific antibodies are treatments that help immune cells recognize and attack lymphoma cells. A large real-world study looked at two bispecific antibodies used in LBCL: epcoritamab (Epkinly, Genmab/AbbVie) and glofitamab (Columvi, Genentech).

Overall, 39% of patients experienced CRS, and 13% experienced ICANS. The study identified practical risk factors doctors can see before treatment. Higher CRS risk was linked to:

• Bulky lymphoma, meaning large tumors
• High lactate dehydrogenase (LDH), a blood marker that can rise with more active lymphoma
• Treatment with epcoritamab compared with glofitamab

Higher risk for more serious CRS was linked to lymphoma found in bone marrow, low platelets, lymphoma in multiple body areas outside lymph nodes, and a history of high-grade CRS with prior CAR T-cell therapy. ICANS risk rose with bulky lymphoma, kidney or liver lab abnormalities, low albumin, and having CRS during bispecific treatment.

These findings can help you and your care team know if you are at a higher risk of side effects from bispecific antibodies. Knowing your risk level can help you plan for closer monitoring, earlier supportive care, or different scheduling to improve safety.

Read this abstract: Risk factors for cytokine release syndrome and neurotoxicity in patients receiving epcoritamab or glofitamab for large B cell lymphoma: A multi-center, retrospective, real world analysis. 

Key takeaways

This new research can help doctors see who may benefit most from CAR T-cell therapy and bispecific antibodies. It also shows who may have a higher risk of side effects. This can help care teams plan treatment and watch patients more closely to improve safety and outcomes for people with LBCL. 

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