PD-1 blockade via pembrolizumab may be an effective salvage treatment for R/R NK/T-Cell Lymphoma

In February 2017, Blood pre-published a study by Yok-Lam Kwong, from Queen Mary Hospital, Hong Kong, and colleagues, which retrospectively analyzed the results of PD-1 blockade by pembrolizumab treatment of R/R Natural Killer/T-Cell Lymphoma (NK/TCL) patients who had previously failed L-asparaginase-based therapies.

Patients who fail L-asparaginase-based treatments usually die, and there is no salvage therapy with proven efficacy for R/R NK/TCLs.

Key Highlights:

• Cohort = seven men, most with advanced R/R NK/TCLs, two relapsed after HSCT, all had received SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) or similar regimens
• Treatment:
  • Pembrolizumab 2 mg/kg every 21 days (one patient received pembrolizumab every 14 days) for a median of seven 21 or 14 day cycles
• Clinical, radiological (PET), morphologic, and molecular criteria (circulating EBV, EBV status, DNA) were used to define response
• Result: Objective response = 100% (n = 7)
  • Median follow-up of 6 months: CR = 71% (n = 5), PR = 29% (n = 2)
  • CR in all criteria in two patients, CR in radiologic and clinical criteria in three patients (one detectable EBV, two undetectable EBV, but with EBV-encoded-RNA-positive cells)
  • Four patients had high PD-1 expression in lymphoma cells (3 of these patients had CR)
  • High PD-1 lymphoma cell expression associated with better response to pembrolizumab
• Adverse events:
  • Grade 2 skin Graft-Versus-Host Disease (GVHD): n = 1 (responded to corticosteroids)

The authors concluded by stating that their data showed that PD-1 blockade via pembrolizumab is a “potent strategy” to be used in the treatment of R/R NK/TCL after L-asparaginase-based treatment failure.

Abstract:

Natural killer (NK)/T-cell lymphomas failing L-asparaginase-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.