Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma.

Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to the FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. This single-arm phase 2 trial (NCT04004221/CTR20170071) assessed the safety, tolerability, and efficacy of tislelizumab in patients with PD-L1-positive urothelial carcinoma who progressed during/following platinum-containing therapy and had no prior PD-(L)1 inhibitor treatment. Patients were considered PD-L1 positive if ≥ 25% of tumor/immune cells expressed PD-L1 when using the VENTANA™ PD-L1 (SP263) assay. The primary endpoint was objective response rate by independent review committee. As of September 16, 2019, 113 patients had a median study follow-up time of 9.4 mo. Most patients (76%) had visceral metastases, including 24% with liver and 23% with bone metastases. Among 104 efficacy-evaluable patients, confirmed objective response rate was 24% (95% confidence interval, 16, 33), including 10 complete and 15 partial responses. Median duration of response was not reached. Among 25 responders, 17/25 (68%) had ongoing responses. Median progression-free survival and overall survival times were 2.1 and 9.8 mo, respectively. The most common treatment-related adverse events were anemia (27%) and pyrexia (19%). Anemia (7%) and hyponatremia (5%) were the only grade 3-4 treatment-related adverse events and occurred in ≥ 5% of patients. Three investigator-assessed deaths were considered to be possibly related to study treatment (hepatic failure, n = 2; respiratory arrest, n = 1). Tislelizumab demonstrated meaningful clinical benefits in patients with previously treated locally advanced or metastatic PD-L1-positive urothelial carcinoma and had a manageable safety profile.

Expression of PD-1, PD-L1, and PD-L2 in posttransplant lymphoproliferative disorder after solid organ transplantation.

We studied the expression of programed death 1 (PD-1) receptor and its ligands (PD-L1/-L2) by immunohistochemistry and its association with clinicopathological features in 81 posttransplant lymphoproliferative disorders (PTLDs) following solid organ transplantation. Overall, 67% (54/81) of the PTLDs were positive in any of the three immunostainings. PD-1 was detected on tumor-infiltrating cells in 41% (33/81) of the PTLDs. PD-L1 was expressed on ≥5% of the tumor cells in 50% (40/80) and PD-L2 in 32% (23/72) of the PTLDs. All Burkitt lymphomas were PD-L1 negative. Expression of PD-L1 tended to be associated with non-germinal center-type of diffuse large B-cell lymphoma (63% vs. 33% in GC-type, p = .14) and latent membrane protein-1+ PTLD (76% vs. 44% in LPM1-, p = .09). Heart recipients had more frequent PTLDs with PD-1+ microenvironment (p = .01). The frequent expression of PD-1 or -L1/-L2 in PTLD warrants further clinical evaluation of the efficacy and safety of PD-(L)1 inhibitors for refractory PTLD.