Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients

OncoImmunology

Konstantin Dragnev¹  Laura J. Tafe¹  Katherine G. Madden¹  Keisuke Shirai¹  Jason Zhu²  Rajan Gupta²  Matthew Labriola²  Shannon McCall²  Daniel J. George²  Tian Zhang²  Matthew Zibelman³  Pooja Ghatalia³  Rajbir Singh⁴  Robin Jacob⁴  Razelle Kurzrock⁵  Sarabjot Pabla⁶  Blake Burgher⁶  Carl Morrison⁶  Mary K. Nesline⁶  Yirong Wang⁶  Wiam Bshara⁶  Vincent Giamo⁶  Sean T. Glenn⁶  Felicia L. Lenzo⁶  Antonios Papanicolau-Sengos⁶  Jonathan Andreas⁶  Jeffrey M. Conroy⁶  Saby George⁷  Bo Xu⁷  Farshid Dayyani⁸  Michelle S Park⁸  Robert Edwards⁸ 

[1] Dartmouth-Hitchcock Medical Center;Duke University;Fox Chase Cancer Center;Meharry Medical College;Moores Cancer Center;OmniSeq, Inc;Roswell Park Comprehensive Cancer Center;University of California;

关键词: nivolumab;    renal cell carcinoma;    pd-1;    pd-l1;    proliferation;    ki-67;   

DOI  :  10.1080/2162402X.2020.1773200

来源: DOAJ

【 摘 要 】

Background Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.

【 授权许可】

Unknown