Hyperprogression after anti-programmed cell death ligand-1 therapy in a patient with recurrent metastatic urothelial bladder carcinoma following first-line cisplatin-based chemotherapy: a case report.

Abstract

BACKGROUND:

Immune checkpoint blockade targeting programmed cell death ligand-1 (PD-L1)/programmed death-1 (PD-1) signaling was approved recently for locally advanced and metastatic urothelial bladder carcinoma (UBC). Some patients experience a very rapid tumor progression, rather than clinical benefit, from anti-PD-L1/PD-1 therapy.

CASE PRESENTATION:

A 58-year-old male diagnosed with non-muscle-invasive bladder cancer 3 years ago received transurethral resection of bladder tumor (TURBT) and intravesical chemotherapy. TURBT was repeated a year later for recurrent and progressive UBC. Following further disease progression, he received a radical cystectomy (RC), pathologically staged as T2bN2M0, and adjuvant cisplatin-containing combination chemotherapy. When his disease progressed to metastatic UBC, he was started on anti-PD-L1 monotherapy and experienced ultrarapid disease progression within 2 months; imaging scans ruled out pseudoprogression. We observed a fourfold increase in tumor growth rate, defined as the ratio of post- to pretreatment rates. Next-generation sequencing of formalin-fixed paraffin-embedded RC tissues showed MDM2 amplification without MDM4 amplification, EGFR aberrations, or DNMT3A alterations. Immunohistochemistry showed grade 2+ PD-L1 labeling intensity of the RC tissues, with 15%-25% and 5%-10% PD-LI immunopositive tumor cells and tumor-infiltrating immune cells, respectively.

CONCLUSION:

Even in cases with PD-L1-positive tumors, MDM2 gene amplification may result in failure of anti-PD-L1 immunotherapy and rapid tumor growth. Therefore, genomic profiling may identify patients at risk for hyperprogression before immunotherapy.

• Authors: Shiyu Mao, Junfeng Zhang, Yadong Guo, Ziwei Zhang, Yuan Wu, Wentao Zhang, Longsheng Wang, Jiang Geng, Yang Yan, Xudong Yao
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 13 Pg. 291-300 ( 2019) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 30666091 (Publication Type: Case Reports, Journal Article)

Chemical References

• Antineoplastic Agents
• B7-H1 Antigen
• Cisplatin

Topics

• Administration, Intravesical
• Antineoplastic Agents (administration & dosage, therapeutic use)
• B7-H1 Antigen (metabolism)
• Cisplatin (administration & dosage, therapeutic use)
• Humans
• Immunotherapy
• Male
• Middle Aged
• Urinary Bladder Neoplasms (metabolism, secondary, therapy)