Dr Lim on the Use of Dexamethasone for Neurotoxicity Prophylaxis in Myeloma

“The use of prophylactic dexamethasone at the time of peak ALC or when ALC exceeded 3 x 10⁹/L through serial ALC testing did not abrogate or significantly reduce the risk of DNT as a whole, central nervous system palsy, or Parkinsonism.”

Kenneth Jin Chang Lim, MBBS, a hematology fellow at St Vincent’s Hospital, discussed findings from a retrospective analysis investigating dexamethasone prophylaxis for immune effector cell delayed neurotoxicity in patients with multiple myeloma with high absolute lymphocyte counts (ALC) after receiving treatment with ciltacabtagene autoleucel (Carvykti).

The central study investigated the use of 10 mg of dexamethasone administered twice daily for a minimum of 3 days when a patient's ALC reached or approached a threshold of 3 x 10⁹/L. Lim explained that the reason for this investigation was to determine whether intervening at the time of peak ALC expansion could reduce the risk of severe adverse effects like Parkinsonism and cranial nerve palsies. However, the prophylaxis did not significantly abrogate the risk of delayed neurotoxicity (DNT). Data showed that the 120-day event-free survival (EFS) rate for any DNT was 82% with dexamethasone (n = 56) vs 76% in a historical cohort of patients who did not receive prophylactic dexamethasone (n = 97; P = .47). The EFS rate for immune effector cell–associated Parkinsonism was 96% in the dexamethasone group compared with 90% in the historical cohort (P = .16).

A second major finding involved the effect of dexamethasone on lymphocyte expansion kinetics. Lim noted that peak ALC values were not significantly reduced with the steroid dose compared with the control treatment, indicating the dosage alone may be insufficient to dampen peak CAR T-cell expansion. Although a slight decrease in the ALC area under the curve (AUC) from day 0 to 28 was observed (P = .037), the peak ALC remained unchanged (P = .196). Furthermore, there were no noticeable differences in the duration or severity of DNT between patients who did vs did not receive the prophylaxis.

Lastly, Lim emphasized the importance of the 3 x 10⁹/L ALC threshold as a predictive biomarker. In the study, ALC peaks below this level demonstrated negative predictive values of 97% with dexamethasone and 99% with the control treatment for the development of any DNT. Despite the strength of this predictor, Lim stated that because prophylactic dexamethasone failed to reduce ALC peaks or neurotoxicity risk, the field must look toward alternative strategies to modulate T-cell function or reduce lymphocyte expansion.

Disclosures: Lim reported no financial conflicts of interest.