Multiple sclerosis outcomes after cancer immunotherapy

Clin Transl Oncol. 2019 Oct;21(10):1336-1342. doi: 10.1007/s12094-019-02060-8. Epub 2019 Feb 20.

Abstract

Introduction: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

Methods: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

Results: We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; two patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors.

Conclusions: Reported MS relapses after ICI are rare, but the adverse events described include rapid neurologic progression and death. Larger and prospective studies are warranted to assess disability and long-term outcomes and outweigh the risks of starting immunotherapy in patients with MS.

Keywords: Immune checkpoint inhibitors; Immune-related adverse events; Multiple sclerosis.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents, Immunological / adverse effects*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Renal Cell / therapy
  • Colorectal Neoplasms / therapy
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Ipilimumab / adverse effects
  • Kidney Neoplasms / therapy
  • Lung Neoplasms / therapy
  • Male
  • Melanoma / therapy
  • Mesothelioma / therapy
  • Mesothelioma, Malignant
  • Middle Aged
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / mortality
  • Neoplasms / complications
  • Neoplasms / therapy*
  • Nivolumab / adverse effects
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • Ipilimumab
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • durvalumab
  • Nivolumab
  • atezolizumab
  • pembrolizumab
  • avelumab