Deep and Durable Response to Nivolumab and Temozolomide in Small-Cell Lung Cancer Associated With an Early Decrease in Myeloid-Derived Suppressor Cells

Clin Lung Cancer. 2021 Jul;22(4):e487-e497. doi: 10.1016/j.cllc.2020.10.018. Epub 2020 Nov 2.

Abstract

Background:: Immune checkpoint inhibitors are now an approved treatment for patients with extensive-stage small cell lung cancer (SCLC), an aggressive and incurable malignancy. However, the median survival for patients remains around 1 year, and treatment in the second line and beyond is associated with a low likelihood of response. There currently are no data regarding the optimal treatment of patients who progress on upfront chemo-immunotherapy, and biomarkers are needed to aid patient selection. Obtaining sufficient tissue for advanced molecular testing is a challenge in SCLC due to often limited or crushed tissue specimens. Reliable blood based biomarkers may augment tissue based testing and allow for repeated assessments that is often not possible with tumor tissue, and changes in the peripheral blood may provide information regarding the tumor microenvironment. Myeloid-derived suppressor cells (MDSC) exert immunosuppressive function and have been investigated as a potential barrier to response to immune checkpoint inhibitor (ICI) therapy. Here we demonstrate that MDSC level and function can be readily assessed in the peripheral blood at multiple time points during treatment with combination immunotherapy and temozolomide.

Results:: This report represents the first case of a patient with refractory SCLC treated with combination nivolumab and temozolomide as part of a clinical trial (NCT03728361), who sustained a deep and durable clinical response that was accompanied by an early decrease in MDSC and improved T cell function (increased CD8+ and CD4+ T cell proliferation). We review the literature regarding use of ICI in SCLC and the evidence supporting MDSC as a possible target to enhance the activity of immunotherapy, and emphasize the importance of assessing immune cell subsets as correlative studies in clinical trials.

Conclusion:: An assessment of MDSC level and function during treatment, as well as other immune cell subsets, should be included in prospective studies to further evaluate these assays as possible blood-based biomarkers.

Keywords: Biomarker; Chemotherapy; Immune checkpoint inhibitor; Immunomodulation; Immunotherapy.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Myeloid-Derived Suppressor Cells / metabolism
  • Nivolumab / administration & dosage
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / pathology
  • Temozolomide / administration & dosage
  • Treatment Outcome

Substances

  • Nivolumab
  • Temozolomide

Associated data

  • ClinicalTrials.gov/NCT03728361