Fitness Landscape of Clonal Hematopoiesis Under Selective Pressure of Immune Checkpoint Blockade.

Conventional cytotoxic therapies increase the risk of clonal hematopoiesis and select for Paired peripheral-blood samples taken before and after treatment with ICB were obtained for 91 patients with either cutaneous melanoma or basal cell carcinoma. Error-corrected sequencing of a targeted panel of genes recurrently mutated in clonal hematopoiesis was performed on peripheral-blood genomic DNA. The average interval between acquisition of the paired samples was 180 days. Forty-one percent of the patients had clonal hematopoiesis at a variant allele frequency (VAF) > 0.01 in the pretreatment sample. There was near-complete agreement in the distribution and burden of clonal hematopoiesis mutations in the paired blood samples, with 87 of 88 mutations identified across the cohort present in paired samples, regardless of the duration between sample collection. The VAF in the paired samples also showed a high correlation, with an There was no expansion of hematopoietic clones or selection for clones at high risk for malignant transformation in patients who received ICB, observations that warrant further validation in larger cohorts. These findings highlight an important difference between ICB and conventional cytotoxic therapies and their respective impacts on premalignant genetic lesions.

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© 2020 by American Society of Clinical Oncology.

Déclaration de conflit d'intérêts

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Peter G. MillerEmployment: Anthem (I) Consulting or Advisory Role: Foundation MedicineArnav MehtaConsulting or Advisory Role: Third Rock VenturesNir HacohenStock and Other Ownership Interests: BioNTech Honoraria: Merck Consulting or Advisory Role: Neon Therapeutics Patents, Royalties, Other Intellectual Property: Patent portfolio for neoantigen vaccinesF. Stephen HodiEmployment: Dana-Farber Cancer Institute Stock and Other Ownership Interests: Apricity, Torque Consulting or Advisory Role: Merck Sharp & Dohme, Novartis, Genentech, EMD Serono, Sanofi, Bayer, Aduro Biotech, Pfizer, Verastem, Bristol Myers Squibb, Takeda, Surface, Compass Therapeutics, Partners Therapeutics, Pionyr, 7Hills Pharma, Torque, Rheos, Amgen, Boston Pharmaceuticals, Checkpoint Therapeutics, Eisai Research Funding: Bristol Myers Squibb (Inst), Merck Sharp & Dohme (Inst), Genentech (Inst), Novartis (Inst) Patents, Royalties, Other Intellectual Property: Patent pending as per institutional policy; patent pending royalties received on MICA-related disorders application to institution per institutional intellectual property policy; angiopoietin-2 biomarkers predictive of anti-immune checkpoint response (Inst); compositions and methods for identification, assessment, prevention, and treatment of melanoma using PD-L1 isoforms; methods of using pembrolizumab and trebananib (Inst) Travel, Accommodations, Expenses: Novartis, Bristol Myers Squibb Other Relationship: Bristol Myers Squibb, GenentechGenevieve M. BolandHonoraria: Novartis, Takeda Oncology Consulting or Advisory Role: NW Biotherapeutics Research Funding: Takeda, Olink Proteomics, Palleon Pharmaceuticals, Takeda Oncology Other Relationship: NektarBenjamin L. EbertStock and Other Ownership Interests: Skyhawk Therapeutics, Exo Therapeutics Consulting or Advisory Role: Exo Therapeutics, Skyhawk Therapeutics Research Funding: Celgene, Deerfield Management Patents, Royalties, Other Intellectual Property: Patents related to the prediction of risk of cardiovascular disease (Inst) No other potential conflicts of interest were reported.