Pembrolizumab-Associated CD8+ Vasculitic Mononeuritis Multiplex in a Patient With Mesothelioma

Our plain-English summary of Pembrolizumab-Associated CD8+ Vasculitic Mononeuritis Multiplex in a Patient With Mesothelioma, by M.C. Baldauf, M. Kapauer, M. Joerger, et al (Neurology® Neuroimmunology & Neuroinflammation, 2021).

The study

• Authors: M.C. Baldauf, M. Kapauer, M. Joerger, L. Flatz, R. Rodriguez, S. Frank, A. Felbecker, S. Hartmann-Fussenegger, T. Hundsberger
• Journal: Neurology® Neuroimmunology & Neuroinflammation
• Published: 2021;8(4)
• Type of article: Case report
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This was a case report about one patient: a 61-year-old woman with pleural mesothelioma, treated by the authors at the Cantonal Hospital St. Gallen, Switzerland. The article did not discuss asbestos. She first received the chemotherapy drugs carboplatin and pemetrexed, then pembrolizumab, an immunotherapy drug that blocks the PD-1 immune checkpoint. Pembrolizumab was restarted after the cancer spread to a rib. It was stopped when small red spots appeared on her skin, and a skin biopsy suggested inflammation of small blood vessels. Two weeks later she developed foot drop on both sides and weakness along the right ulnar nerve. Nerve tests showed severe nerve-fiber damage, and ultrasound showed swelling in several nerves. Laboratory, spinal fluid and urine tests were normal. A nerve biopsy confirmed small vessel vasculitis, with CD8+ T cells dominating the inflammation. Steroids did not relieve her symptoms, and severe pain persisted after cyclophosphamide. The authors concluded this was a pembrolizumab-associated nerve vasculitis. They noted that earlier chemotherapy may have added to her sensory loss, and that the condition's rarity made comparison with the literature not feasible.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 61-year-old woman with pleural mesothelioma (stage cT3cN0cM0), treated at the Cantonal Hospital St. Gallen, Switzerland
• Exposure: Not asbestos. The exposure studied was cancer treatment: carboplatin/pemetrexed chemotherapy, then maintenance with the anti-PD-1 immune checkpoint inhibitor pembrolizumab. Pembrolizumab was later readministered every 3 weeks for 15 cycles.
• Main results:
  • After pembrolizumab was readministered, skin petechiae developed. A skin biopsy showed perivascular lymphocyte infiltrates suggesting a late-stage small vessel vasculitis.
  • Two weeks after treatment was stopped, the patient had bilateral foot drop and paresis in the distribution of the right ulnar nerve.
  • Motor nerve conduction studies showed severe axonal damage in the right median and ulnar nerves and in both peroneal and tibial nerves.
  • Nerve ultrasound showed multifocal fascicular swelling. The right sural nerve had a cross-sectional area of 5 mm2 (norm less than 2 mm2).
  • Laboratory, CSF and urine analyses were normal.
  • The sural nerve biopsy showed small vessel vasculitis, with CD8+ T cells dominating the immune infiltrate.
  • Steroids failed to relieve symptoms. After 6 cycles of IV cyclophosphamide, severe allodynia persisted, and pain medications showed only moderate efficacy.
  • The authors stated that the side effects evolved over around 30 weeks after re-exposure to the drug, which they described as particularly long.
• The authors' conclusion: The authors described this as a histologically proven pembrolizumab-associated sensorimotor nonsystemic vasculitic mononeuritis multiplex. They considered a systemic vasculitis and a paraneoplastic origin unlikely. They stated that optimal treatment remains to be defined.
• Limitations the authors state:
  • The authors stated that, because of the rarity of the reported case, a comparison with the literature is not feasible.
  • An accompanying chemotherapy-induced polyneuropathy may have contributed to the sensory impairment.
  • Whether the preceding neurotoxic chemotherapy triggered this side effect remains speculative.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Mesothelioma.

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