Stefan K Barta1, Jasmine Zain2, Alexander W MacFarlane3, Sonali M Smith4, Jia Ruan5, Henry C Fung6, Carlyn R Tan6, Yibin Yang3, R Katherine Alpaugh7, Essel Dulaimi8, Eric A Ross9, Kerry S Campbell3, Nadia Khan6, Rawat Siddharta10, Nathan H Fowler11, Richard I Fisher6, Yasuhiro Oki11. 1. Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA; Department of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA. Electronic address: stefan.barta@uphs.upenn.edu. 2. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Cancer Center, Duarte, CA. 3. Department of Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, PA. 4. Department of Hematology/Oncology, University of Chicago, Chicago, IL. 5. Department of Hematology and Oncology, Weill Cornell Medicine, New York, NY. 6. Department of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA. 7. Protocol Support Laboratory, Fox Chase Cancer Center, Philadelphia, PA. 8. Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA. 9. Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA. 10. Office of Clinical Research, Fox Chase Cancer Center, Philadelphia, PA. 11. Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX.
Abstract
BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are frequently expressed in T-cell lymphomas. This provides a rationale for exploration of immune checkpoint inhibitors in the management of T-cell lymphomas. PATIENTS AND METHODS: In this phase II single-arm multicenter trial, patients with relapsed or refractory systemic T-cell lymphoma were treated with 200 mg pembrolizumab intravenously every 21 days. The primary endpoint was progression-free survival (PFS). The secondary endpoints were response rate, overall survival, response duration, and safety. We assessed PD-L1, p-AKT expression, and peripheral blood immune cells as potential predictive biomarkers. RESULTS: Of 18 enrolled patients, 13 were evaluable for the primary endpoint. The trial was halted early after a preplanned interim futility analysis. The overall response rate was 33% (95% confidence interval [CI], 9%-55%); 4 patients achieved a complete response (27%; 95% CI, 5%-49%). The median PFS was 3.2 months (95% CI, 1.2-3.7 months), and the median overall survival was 10.6 months (95% CI, 3.2-100 months). The median duration of response was 2.9 months (95% CI, 0-10.1 months). Two of the 4 complete responders remain in remission > 15 months. Rash was the most common adverse event (17%; n = 3). The most common ≥ grade 3 treatment-emergent adverse events were rash and pneumonitis (11%; n = 2 each). Neither PD-L1 nor p-AKT expression were associated with outcomes. However, a higher relative frequency of CD4+ T lymphocytes pre-treatment was associated with improved PFS (hazard ratio, 0.15; 95% CI, 0.03-0.74). CONCLUSION: Pembrolizumab demonstrated modest single-agent activity in relapsed or refractory T-cell lymphoma.
BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are frequently expressed in T-cell lymphomas. This provides a rationale for exploration of immune checkpoint inhibitors in the management of T-cell lymphomas. PATIENTS AND METHODS: In this phase II single-arm multicenter trial, patients with relapsed or refractory systemic T-cell lymphoma were treated with 200 mg pembrolizumab intravenously every 21 days. The primary endpoint was progression-free survival (PFS). The secondary endpoints were response rate, overall survival, response duration, and safety. We assessed PD-L1, p-AKT expression, and peripheral blood immune cells as potential predictive biomarkers. RESULTS: Of 18 enrolled patients, 13 were evaluable for the primary endpoint. The trial was halted early after a preplanned interim futility analysis. The overall response rate was 33% (95% confidence interval [CI], 9%-55%); 4 patients achieved a complete response (27%; 95% CI, 5%-49%). The median PFS was 3.2 months (95% CI, 1.2-3.7 months), and the median overall survival was 10.6 months (95% CI, 3.2-100 months). The median duration of response was 2.9 months (95% CI, 0-10.1 months). Two of the 4 complete responders remain in remission > 15 months. Rash was the most common adverse event (17%; n = 3). The most common ≥ grade 3 treatment-emergent adverse events were rash and pneumonitis (11%; n = 2 each). Neither PD-L1 nor p-AKT expression were associated with outcomes. However, a higher relative frequency of CD4+ T lymphocytes pre-treatment was associated with improved PFS (hazard ratio, 0.15; 95% CI, 0.03-0.74). CONCLUSION:Pembrolizumab demonstrated modest single-agent activity in relapsed or refractory T-cell lymphoma.