FCCC LOGO Faculty Publications
Barta SK , Zain J , MacFarlane AW4th , Smith SM , Ruan J , Fung HC , Tan CR , Yang Y , Alpaugh RK , Dulaimi E , Ross EA , Campbell KS , Khan N , Siddharta R , Fowler NH , Fisher RI , Oki Y
Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma
Clin Lymphoma Myeloma Leuk. 2019 Jun;19(6) :356-364 e3
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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.
Notes
2152-2669 Barta, Stefan K Zain, Jasmine MacFarlane, Alexander W 4th Smith, Sonali M Ruan, Jia Fung, Henry C Tan, Carlyn R Yang, Yibin Alpaugh, R Katherine Dulaimi, Essel Ross, Eric A Campbell, Kerry S Khan, Nadia Siddharta, Rawat Fowler, Nathan H Fisher, Richard I Oki, Yasuhiro Journal Article United States Clin Lymphoma Myeloma Leuk. 2019 Jun;19(6):356-364.e3. doi: 10.1016/j.clml.2019.03.022. Epub 2019 Apr 3.