title: Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy.
abstract: Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well asPDL1/PDL2/JAK2amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containingPD-L1,PD-L2andJAK2. Of interest,PD-L1,PD-L2andJAK2amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that includePD-L1amplification and high tumour mutational burden.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, La Jolla, CA, USA; Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA; Cancer Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sadakatsu
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, La Jolla, CA, USA; Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Goodman
authors.affiliation: Department of Dermatology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Cohen
authors.affiliation: Sequenom Laboratories, La Jolla, CA, USA.
authors.forename: Taylor J
authors.initials: TJ
authors.lastname: Jensen
authors.affiliation: Sequenom Laboratories, La Jolla, CA, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Ellison
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Frampton
authors.affiliation: Foundation Medicine, Cambridge, MA, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Miller
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, La Jolla, CA, USA; Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Sandip P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, La Jolla, CA, USA; Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock