Suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma.suppressive dexamethasone (SupDex) to prevent delayed non-icans delayed neurotoxicity (DNT) post ciltacabtagene-autoleucel(cilta-cel) in patients with relapsed myeloma.

Abstract

Abstract Introduction: Cilta-cel has demonstrated unprecedented efficacy for multiple myeloma. However, DNTs, mainly in the form of cranial nerve palsies (CNP) and Parkinsonism, occur in 5-10% of patients and remain a significant source of morbidity and mortality. We have identified that the maximum(max) absolute lymphocyte count (ALC), a surrogate for CAR-T cell expansion, is associated with a higher risk of developing DNT. We herein report on the efficacy and safety of dexamethasone as prophylaxis for DNT for patients with high ALC post cilta-cel. Methods: In this single-center retrospective study, we reviewed 56 patients(pts) treated at our center with cilta-cel for relapsed MM between January 2025 to April 2025. Sequential ALCs were followed from day of infusion until day 30, and all patients with a max ALC > 3 k/uL were to receive 3 consecutive days of SupDex at a dose of 20 mg/d. All pts were followed for at least 90 days post cilta-cel. Results: Amongst the 56 pts who were treated with cilta-cel n=56, 31 received SupDex,(n=29 for max ALC >3 k/uL, n=2 received dex for ALC <3k/uL) and 25 did not receive Supdex (ALC <3 k/uL n=24, ALC >3 k/uL, n=1). SupDex was started at a median of 11 days post-cilta-cel (range 10-15) and either the same day or next day of ALC > 3ku/L. There were no significant differences in median age, high marrow burden, prior lines of therapy, or bridging therapy between the pts who received SupDex vs those who did not (No-Dex cohort) (n=25). When compared to the pts in the No-Dex cohort, pts in the SupDex cohort had higher incidence of CRS (96.8% vs 64%, p=0.003), use of tociluzimab (64.5 % vs 36%, p=0.034) and previous use of dex for CRS (51.6% vs 24%, p=0.035). There was also a trend for a higher incidence of ICANS (22.6% vs 8%, p=0.167). Max ALC was higher in the Dex cohort vs No-Dex cohort (median 5.4 k/uL(1.7-63.7) vs 1.5k/uL(0.3-5.98), p=<0.001). Twelve pts out of the 56(21.4%) who received cilta-cel developed DNT (cranial nerve palsy, n=9(16%), Parkinsonism, n=3(5.3%), and all of them were in the SupDex cohort and had max ALC >3 k/uL. There were no instances of DNT in the No-Dex cohort (21% vs 0 p <.001). The characteristics of the CNP were similar what we previously reported prior to the Supdex intervention but were of delayed onset post cilta-cel (day 25 (range 17-71) vs day 17.5 range (14-32)). By D90 in the Supdex cohort, most of the CNP (66%) had resolved and the other 3 were improved. Similarly, 2 of the 3 cases of Parkinsonism were improved and mild by D90 but one died before D90 from pneumonia with unresolved Parkinsons. The incidence of infections up to D30 days was similar in both cohorts (19.4% vs 20 %). There were no instances of NRM in the No-dex cohort. Finally, pts who received SupDex and developed DNT(n=12) had a higher max ALC and max ALC slope compared to those with Supdex who did not have DNT (n=19) (7.08 vs 4.6 k/uL, p=0.023) and higher max ALC slope (5.36 vs 3.37, p=0.04) suggesting Supdex was not effective at curbing CART expansion for those patients. Conclusion: Our findings confirm the association between max ALC and DNT. However, in this single center cohort, prophylaxis with Supdex for pts with max ALC>3 k/uL did not appear to reduce the risk of DNT although it was not associated with infectious complications or increased NRM. Evaluating other agents for the prevention of DNT in pts at higher risk of DNT is warranted.