Tumor Mutation Burden and Efficacy of Nivolumab Monotherapy and in Combination With Ipilimumab in Small Cell Lung Cancer
By M. Hellmann, M. Callahan, M. Awad, E. Calvo, P. Ascierto, A. Atmaca, N. Rizvi, F. Hirsch, G. Selvaggi, J. Szustakowski and 6 more. Cancer Cell, 2018
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SUMMARY 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 mutation burden (TMB) 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 TMB. Nivolumab plus ipilimumab appeared to provide a greater clinical benefit than nivolumab monotherapy in the high TMB tertile.
Subfields: Epidemiology, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/47cd9a015e1a0d625e84ed87bd3980d01b35317c
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Citations in the corpus
- Genomic features of response to combination immunotherapy in patients with advanced non-small cell lung cancer (2018, neutral): “Similar results were seen in a recent report of patients with small cell lung cancer treated with PD-1 plus CTLA-4 blockade (Hellmann et al., 2018), suggesting the importance of TMB as biomarker for combination immunotherapy across lung cancers.”
- The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker (2020, background): “…et al., 2016; Shitara et al., 2018; Siefker-Radtke et al., 2018) Unfortunately, ICIs can also cause a number of unique immunerelated toxicities (Patel and Kurzrock, 2015; Postow and Hellmann, 2018) as well as accelerated progression, termed hyperprogression, in a subset of treated individuals.”
- Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities (2021, background): “While ICB is now a standard-of-care for SCLC, predictive biomarkers for this therapeutic class have remained elusive, with evidence supporting (and opposing) TMB and PD-L1 expression (Chung et al., 2020; Hellmann et al., 2018).”