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Purpose <p>The cross-sectional AILEEN study evaluated long-term cognitive function after immune checkpoint inhibition (ICI) for melanoma and compared outcomes between neoadjuvant combination therapy (ipilimumab/nivolumab) versus adjuvant monotherapy (nivolumab or pembrolizumab).</p> Methods <p>Patients with stage III/IV melanoma were invited approximately two years after ICI initiation. Patients completed the online Amsterdam Cognition Scan and questionnaires on self-reported cognitive problems, fatigue, anxiety, and depression. Scores were evaluated at group- and individual-level against cancer-free norm groups and well-established cutoffs. Prevalences of cognitive impairment were compared to estimated false-positive rates accounting for the number and correlation of tests.</p> Results <p>Patients treated with ICI (<i>N</i> = 107) showed significantly worse verbal memory, processing speed, and executive functioning and reported clinically meaningful lower cognitive function at group-level compared to normative data. At individual-level, 34% were classified as cognitively impaired (exceeding the false-positive rate of 20.6%), and 36% reported clinically relevant cognitive problems. Patients who received neoadjuvant combination therapy (<i>N</i> = 29) showed significantly worse group-level executive functioning and processing speed, whereas those who received adjuvant monotherapy (<i>N</i> = 43) performed comparable to normative data. At individual-level, cognitive impairment was more prevalent (38% vs. 21%), however, rates of self-reported cognitive problems (24% vs. 38%), fatigue (10% vs. 23%), and anxiety (0% vs. 11%) were lower in patients treated with neoadjuvant combination versus those treated with adjuvant monotherapy.</p> Conclusions <p>Long-term cognitive and psychosocial problems are prevalent in ICI-treated patients with melanoma. Neoadjuvant combination therapy was associated with greater objective cognitive impairment yet fewer self-reported problems than adjuvant monotherapy.</p> Implications for Cancer Survivors <p>While these hypothesis-generating findings warrant prospective validation, alertness for cognitive problems is important.</p>

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Long-term cognitive function after treatment with immune checkpoint inhibition for melanoma

  • 期刊论文

  • 发表日期：

    2026年5月5日

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  • Maryse J. Luijendijk,
  • Elaine A. C. Albers,
  • Mees Egeler,
  • Lonneke V. van de Poll-Franse,
  • Christian U. Blank,
  • Sanne B. Schagen

摘要

Purpose

The cross-sectional AILEEN study evaluated long-term cognitive function after immune checkpoint inhibition (ICI) for melanoma and compared outcomes between neoadjuvant combination therapy (ipilimumab/nivolumab) versus adjuvant monotherapy (nivolumab or pembrolizumab).

Methods

Patients with stage III/IV melanoma were invited approximately two years after ICI initiation. Patients completed the online Amsterdam Cognition Scan and questionnaires on self-reported cognitive problems, fatigue, anxiety, and depression. Scores were evaluated at group- and individual-level against cancer-free norm groups and well-established cutoffs. Prevalences of cognitive impairment were compared to estimated false-positive rates accounting for the number and correlation of tests.

Results

Patients treated with ICI (N = 107) showed significantly worse verbal memory, processing speed, and executive functioning and reported clinically meaningful lower cognitive function at group-level compared to normative data. At individual-level, 34% were classified as cognitively impaired (exceeding the false-positive rate of 20.6%), and 36% reported clinically relevant cognitive problems. Patients who received neoadjuvant combination therapy (N = 29) showed significantly worse group-level executive functioning and processing speed, whereas those who received adjuvant monotherapy (N = 43) performed comparable to normative data. At individual-level, cognitive impairment was more prevalent (38% vs. 21%), however, rates of self-reported cognitive problems (24% vs. 38%), fatigue (10% vs. 23%), and anxiety (0% vs. 11%) were lower in patients treated with neoadjuvant combination versus those treated with adjuvant monotherapy.

Conclusions

Long-term cognitive and psychosocial problems are prevalent in ICI-treated patients with melanoma. Neoadjuvant combination therapy was associated with greater objective cognitive impairment yet fewer self-reported problems than adjuvant monotherapy.

Implications for Cancer Survivors

While these hypothesis-generating findings warrant prospective validation, alertness for cognitive problems is important.