PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing L-asparaginase

Yok-Lam Kwong, Thomas S.Y. Chan, Daryl Tan, Seok Jin Kim, Li-Mei Poon, Benjamin Mow, Pek-Lan Khong, Florence Loong, Rex Au-Yeung, Jabed Iqbal, Colin Phipps and Eric Tse

Key points

  • NK/T-cell lymphomas failing L-asparaginse, generally fatal, showed a high complete response rate to PD1 blockade with pembrolizumab.

  • Comprehensive clinical, radiologic, pathologic and molecular assessment showed different patterns of complete and partial responses.


Natural killer (NK)/T-cell lymphomas failing L-asparaginse-regimens have no known salvage and are almost invariably fatal. Seven male NK/T-cell lymphoma patients (age: 49, 31–68, years) failing 2 (1–5) regimens (including L-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, HSCT, in 2 cases), were treated with the anti-programmed-death-1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic and molecular (circulating Epstein-Barr virus, EBV, DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CR, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded-RNA-positive cells in lesions comprising predominantly CD3+CD4+ and CD3+CD8+ T-cells (which ultimately disappeared, suggesting they represented pseudo-progression); and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After 7 (2–13) cycles of pembrolizumab and a follow-up of 6 (2–10) months, all five CR patients were still in remission. The only adverse event was grade II skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1-ligand was strong in four cases (three achieving CR) and weak in one case (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing L-asparaginase-regimens.

  • Submitted December 13, 2016.
  • Accepted January 24, 2017.