A new study showed that structural rearrangements disrupting the 3’-UTR of PD-L1 (PD-L1MUT) is a potential new biomarker for response to anti–PD-1 therapy for patients with relapsed or refractory natural killer/T-cell lymphoma.
Previous studies had shown a complete response rate of about 50% in these patients, however, many patients were exposed to potential side effects without receiving any clinical benefit.
The study was a retrospective examination of 19 patients with relapsed/refractory natural killer/T-cell lymphoma treated with pembrolizumab. All patients underwent genetic analysis to look for novel biomarkers of response. Two additional patients underwent prospective screening.
Of the 19 patients, 36.8% had complete response, 10.5% had partial response, and 5.3% had stable disease. Overall response rate was 47.4%. Among those patients with complete or partial response, the long-term clinical benefit was an average of 28.3 months.
According the analyses, the most frequent somatic mutations were PD-L1MUT, which occurred in 4 cases.
“Importantly, PD-L1MUT was the only gene alteration that was significantly enriched in the tumoral tissues of patients who responded to pembrolizumab compared to those who did not (P =.03, Fisher’s exact test),” the researchers wrote.
PD-L1MUT achieved 100% specificity in identifying responders to pembrolizumab. Sensitivity was modest at 44%. Patients with PD-L1MUT also had significantly better overall survival that those with PD-L1 wild-type when treated with pembrolizumab.
“We found that PD-L1 was expressed in almost all our tumoral specimens (18/19 cases),” the researchers noted. “These results clearly showed that PD-L1 positivity is less ideal than PD-L1MUT as a biomarker for response to [immune checkpoint inhibitor] therapy in NKTCL.”
Of the 2 prospectively screened patients, 1 was found to be PD-L1MUT. He was treated with 3 mg/kg pembrolizumab every 3 weeks and achieved a metabolic complete response after his third cycle.
Lin JQ, Huang D, Tang T, et al. Whole-genome sequencing identifies responders to pembrolizumab in relapse/refractory natural-killer T cell lymphoma. Leukemia. Published online August 5, 2020. doi:10.1038/s41375-020-1000-0