Rapid CAR-T Expansion Linked to Delayed Neurotoxicity in Myeloma

A new multi-center study had important findings that may help improve diagnosis with a simple blood test to identify higher-risk multiple myeloma patients early. These study findings also suggest how one common event after CAR-T infusion can increase the risk of delayed neurotoxicity. 

What is ciltacabtagene autoleucel (cilta-cel)?

Ciltacabtagene autoleucel (Carvykti, Janssen), often called cilta-cel, is a type of chimeric antigen receptor (CAR) T-cell therapy. CAR-T therapy uses a patient’s own immune T cells to fight cancer. The T cells are collected, engineered to target cancer cells, and then infused back into the body.

Cilta-cel has shown deep and long-lasting responses in people with relapsed or refractory multiple myeloma. However, it can cause unique side effects, including delayed neurotoxicity.

What is delayed neurotoxicity (DNT)?

Delayed neurotoxicity (DNT) refers to nervous system side effects that happen days to weeks after CAR-T infusion. In this study, it happened in 11% of patients. It also causes specific neurologic effects such as cranial nerve palsy (8%) and parkinsonism (3%).

Even after much research on CAR-T and its side effects, researchers keep studying it to improve its outcomes

After infusion, CAR T cells multiply in the body. This process is called expansion. Researchers wanted to know whether higher or faster expansion increases the risk of DNT.

The study included 256 patients treated with commercial cilta-cel between 2022 and 2024. Of those, 54 patients had detailed CAR-T expansion measurements using flow cytometry. 

The median progression-free survival (PFS) was 28.7 months, showing strong treatment effectiveness overall.

Rapid and robust CAR-T expansion associated with a higher risk of delayed neurotoxicity

In the smaller cohort where CAR-T levels were directly measured:

• Peak CAR-T expansion was significantly higher in patients who developed DNT.
• It was also higher in those who developed ICANS (immune effector cell-associated neurotoxicity syndrome), another neurologic side effect.

However, peak expansion was not linked to response rates or time to progression. This suggests that more expansion does not necessarily mean better long-term outcomes but it may increase toxicity risk.

Can a simple blood test help predict risk?

Researchers also studied absolute lymphocyte count (ALC), a routine blood test that measures the number of lymphocytes in the blood.

They found that:

• Patients who developed DNT had much higher peak ALC levels.
• Those who developed Parkinsonism had especially high ALC values.
• A rapid rise in ALC between days 7 and 12 after infusion was strongly linked to DNT.

This means ALC may serve as a practical, accessible way to estimate CAR-T expansion and identify patients at higher risk.

What ALC levels signal higher risk?

The study identified two clinically useful thresholds:

1. ALC ≥ 3000/μL between days 7 to 21
2. ALC ≥ 2500/μL between days 8 to 12 with at least a two-fold increase from prior levels

Together, these thresholds identified 81% of DNT cases while excluding 59% of patients who did not develop DNT. These markers could help guide earlier monitoring or preventive strategies.

What does this mean for patients with multiple myeloma?

CAR-T therapy remains a powerful treatment option for relapsed or refractory multiple myeloma. Most patients do not develop delayed neurotoxicity.

However, this research highlights that faster immune cell expansion may be associated with increased neurologic risk. Importantly, a simple blood test may help doctors identify higher-risk patients early.

This opens the door to more personalized monitoring and potentially earlier interventions without compromising the treatment’s effectiveness.

Getting closer to a safer CAR-T therapy

The goal of modern myeloma care is finding a specific therapy to diminish the side effects as much as possible while obtaining deeper responses. By identifying measurable warning signs early, care teams can protect patients while preserving the benefits of CAR-T therapy.

As research continues, the future of multiple myeloma treatment is becoming more precise, more proactive, and more patient-centered, and that progress matters.

Stay tuned for more articles like this, and all of our planned activities for the Multiple Myeloma Awareness Month and subscribe to our weekly newsletter so you don’t miss anything. 

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Sources: Rapid peak CAR-T expansion is associated with delayed neurotoxicity following ciltacabtagene autoleucel in multiple myeloma