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Brain Atrophy and Leukoencephalopathy Following Tarlatamab: Case Report.

Kiriko Onishi1, Toki Kitano1, Yusuke Fujioka1

  • 1Department of Respiratory Medicine Okayama Rosai Hospital Okayama Japan.

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|October 27, 2025
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Summary

This case study highlights potential neurological side effects, including cerebral atrophy and leukoencephalopathy, associated with tarlatamab treatment in a patient with small cell lung cancer and brain metastases.

Keywords:
brain atrophyimmune effector cell‐associated neurotoxicity syndromeleukoencephalopathytarlatamabwhole‐brain radiotherapy

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Area of Science:

  • Oncology
  • Neurology
  • Radiotherapy

Background:

  • Extensive-stage small cell lung cancer (SCLC) presents significant treatment challenges, often involving brain metastases.
  • Standard treatments include chemotherapy, immunotherapy, and radiotherapy, with limited options for refractory disease.

Purpose of the Study:

  • To report a rare case of early-onset cerebral atrophy and leukoencephalopathy in a patient with SCLC brain metastases treated with tarlatamab.
  • To investigate potential neurological adverse events associated with tarlatamab in combination with whole-brain radiotherapy.

Main Methods:

  • A case report of a 74-year-old female with extensive-stage SCLC and brain metastases.
  • Review of treatment history including carboplatin, etoposide, atezolizumab, amrubicin, nogitecan, stereotactic radiotherapy, whole-brain radiotherapy, and tarlatamab.
  • Analysis of neuroimaging (MRI, FLAIR) and clinical response following tarlatamab administration.

Main Results:

  • The patient developed disorientation, rapid cerebral atrophy, ventricular enlargement, and periventricular hyperintensity after tarlatamab treatment.
  • Metastatic lesions showed shrinkage, but neurological symptoms did not improve with dexamethasone.
  • The observed neurological events were attributed to the combined effects of whole-brain radiotherapy and tarlatamab.

Conclusions:

  • Tarlatamab, particularly in conjunction with whole-brain radiotherapy, may pose a risk for severe neurological toxicity in patients with brain metastases.
  • Patients with brain metastases receiving tarlatamab require close neurological monitoring for potential adverse events.
  • Further research is warranted to understand and mitigate the neurotoxicity risks of novel SCLC therapies.