TY - JOUR
T1 - Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma
AU - Barta, Stefan K.
AU - Zain, Jasmine
AU - MacFarlane, Alexander W.
AU - Smith, Sonali M.
AU - Ruan, Jia
AU - Fung, Henry C.
AU - Tan, Carlyn R.
AU - Yang, Yibin
AU - Alpaugh, R. Katherine
AU - Dulaimi, Essel
AU - Ross, Eric A.
AU - Campbell, Kerry S.
AU - Khan, Nadia
AU - Siddharta, Rawat
AU - Fowler, Nathan H.
AU - Fisher, Richard I.
AU - Oki, Yasuhiro
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Angioimmunoblastic lymphoma
KW - Immune checkpoint blockade
KW - Immunotherapy
KW - PD-1 inhibitor
KW - Peripheral T cell lymphoma
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U2 - 10.1016/j.clml.2019.03.022
DO - 10.1016/j.clml.2019.03.022
M3 - Article
C2 - 31029646
AN - SCOPUS:85064575092
SN - 2152-2650
VL - 19
SP - 356-364.e3
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 6
ER -