Recovery and Rechallenge after Neurological Immune-related Adverse Events from Immune Checkpoint Inhibitors
Ali-Musa Jaffer1, Sepideh Mokhtari1, Yolanda Pina1, Edwin Peguero1, Peter Forsyth1, David Iacono1, Husayn Jaffer2, Muhammad Jaffer1
1Moffitt Cancer Center, 2University of Florida
Objective:
Analyze recovery metrics and safety of rechallenge after neurological immune-related adverse events from immune checkpoint inhibitor use.
Background:
Immune checkpoint inhibitors (ICIs) are a foundational therapy in immunogenic solid tumors. Neurological immune-related adverse events (nIRAE) from ICI therapy often impact survival and treatment approaches. More data is needed on longitudinal outcomes and the safety of rechallenge in ICI-related nIRAE, especially in patients with minimal residual disability.
Design/Methods:
We retrospectively reviewed 49 cancer patients who developed ICI-related nIRAE at Moffitt Cancer Center between 2018-2025. Data collected included cancer subtype, ICI class used, nIRAE phenotype, time from ICI initiation to nIRAE onset, survival time after nIRAE, modified Rankin Scale (mRS) at nadir, mRS at 6 months post-nIRAE, and outcomes of any ICI rechallenge.
Results:
Cancer subtypes included melanoma (N=28), lung (N=12), and renal (N=9). ICI classes included PD‑1 (43%), PD‑1/CTLA‑4 (43%), PD-L1 (8%), and PD‑1/LAG‑3 (6%). Mean time from ICI initiation to nIRAE onset was 4.6 ± 2.2 months. Mean survival time after nIRAE was 16.6 ± 4.2 months. nIRAE phenotypes included neuropathy (N=22), myositis (N=17), encephalitis (N=10), myasthenia gravis (N=5), demyelinating (N=2), and vasculitis (N=1). Mean mRS at nadir was 3.6 ± 0.4. Mean mRS after 6 months was significantly lower at 2.7 ± 0.6 (p=0.013). 48% of patients had minimal to no disability after 6 months (mRS ≤ 1). ICI was rechallenged in 5 patients in our cohort (4 melanoma and 1 renal, all with neuropathy and mRS at 6 months post-nIRAE of 1). None of these patients experienced nIRAE recurrence.
Conclusions:
ICI-related nIRAE demonstrated significant functional improvement in our cohort after 6 months, with 48% of cases achieving minimal to no disability. In a subset of patients with the neuropathy phenotype and good functional status, ICI rechallenge was well‑tolerated with no recurrence of nIRAE, supporting a patient‑centered, individualized approach in select cases.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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