Tumor Mutational Burden and Efficacy of Nivolumab Monotherapy and in Combination with Ipilimumab in Small-Cell Lung Cancer

Cancer Cell. 2018 May 14;33(5):853-861.e4. doi: 10.1016/j.ccell.2018.04.001. Epub 2018 May 3.


Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks). Efficacy of nivolumab ± ipilimumab was enhanced in patients with high tumor mutational burden. Nivolumab plus ipilimumab appeared to provide a greater clinical benefit than nivolumab monotherapy in the high tumor mutational burden tertile.

Keywords: CTLA-4; PD-1; biomarkers; clinical trial; immunotherapy; ipilimumab; nivolumab; small cell lung cancer; tumor mutation burden.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Exome Sequencing
  • Female
  • Humans
  • Ipilimumab / administration & dosage*
  • Ipilimumab / pharmacology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Nivolumab / administration & dosage*
  • Nivolumab / pharmacology
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics
  • Treatment Outcome
  • Tumor Burden / drug effects


  • Ipilimumab
  • Nivolumab