Dexamethasone Prophylaxis is a Promising Intervention Therapy for Patients With RRMM Receiving Cilta-Cel

Key Takeaways:

• In the control group of 30 patients with relapsed or refractory multiple myeloma (RRMM) being treated with ciltacabtagene autoleucel (cilta-cel), 9 (30%) developed excessive absolute lymphocyte count (ALC) expansion. Five (55.6%) of these patients experienced atypical neurologic events, suggesting that ALC is a good indicator of immune-related adverse events.
• In the intervention group of 23 patients, 7 (30.4%) developed excessive ALC expansion and were subsequently treated with dexamethasone. ALC levels lowered within 3 days of treatment, and 1 patient experienced a neurologic event.
• A median overall survival (OS) was not reached for patients treated with dexamethasone. The median OS for patients who were not treated with dexamethasone was 104 days.

Cilta-cel is a type of chimeric antigen receptor (CAR) T cell therapy that has shown to be an effective treatment option for patients with RRMM. However, it has also been associated with immune-related adverse events such as immune effector cell–associated neurotoxicity syndrome (ICANS) and atypical (non-ICANS) neurologic events. This study observed outcomes for patients treated with cilta-cel and focused on the role of ALC in predicting treatment-related mortality and atypical neurologic events.

This retrospective study assessed 53 patients with RRMM who were treated with cilta-cel at the Colorado Blood Center Institute (CBCI) between September 2023 and January 2025. Patients were broken into 2 groups: a preintervention (nonintervention) group and an intervention group. Patients in the intervention group received dexamethasone prophylaxis when they demonstrated elevated ALC levels. The preintervention group included 30 patients while the intervention group had 23 patients.

Neurologic Events and Mortality Tied to Excessive ALC Expansion

In the preintervention group, 9 (30%) patients developed excessive ALC expansion (ALC > 5 × 103/μL). Of this group, 5 (55.6%) patients suffered atypical neurologic events and died due to treatment-related complications.

In the intervention group, 7 (30.4%) patients developed excessive ALC expansion and received subsequent treatment with dexamethasone. Only 1 patient experienced a neurologic event, and death resulted from an infection that occurred 9 months after treatment. ALC levels were reduced within 3 days after patients received dexamethasone.

A median OS was not reached for patients who developed excessive levels of ALC and were subsequently treated with dexamethasone. For patients who experienced excessive ALC expansion but were not treated with dexamethasone, the median OS was 104 days.

Dexamethasone May Mitigate Immune-Related Adverse Events

High levels of ALC rising to > 5 × 103/μL led to increased treatment-related mortality and a higher rate of atypical neurologic events, making ALC expansion a notable identifier of patients with high risk to these adverse events.

Using dexamethasone to treat patients with excessive ALC expansion seemed to mitigate immune-related adverse events and improve patient outcomes. The authors said using dexamethasone to reduce ALC levels “offers a low-cost, easily accessible intervention that may improve safety for patients undergoing cilta-cel therapy.”

Reference

Forsberg PA, Turner JA, Meyer M, et al. Dexamethasone prophylaxis for excessive lymphocyte expansion after cilta-cel in multiple myeloma. Blood Adv. 2026;10(10):3629–3639. doi:10.1182/bloodadvances.2025018639