Combination Therapy Shows Promising Results in Relapsed or Refractory Natural Killer/T-Cell Lymphoma

Strategic Insights -

Patients with relapsed or refractory natural killer/T-cell lymphoma (R/R NKTL) have limited treatment options, but a new combination therapy of epigenetic therapy with an anti-PD-1 antibody shows promising results. The study, published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR), suggests that the combination therapy can potentially be curative for a subset of patients who experience recurrence and highlights the utility of DNMT inhibitors in switching on the immune response through viral mimicry.

Key Takeaways:

  • The study investigated the combination of PD-1 inhibitor sintilimab with DNMT inhibitors decitabine or azacitidine in 21 patients with R/R NKTL who initially responded to anti-PD-1 therapy but subsequently experienced disease recurrence.
  • Of the 21 patients, 10 had complete remission and four had a partial response following treatment with the combination.
  • The two-year overall survival rate was 50.2%.
  • Preclinical data showed that DNMT inhibitors reversed immune resistance by demethylating (activating) endogenous retroviral elements, causing an immune response through the type 1 interferon signaling pathway.
  • The study highlights the utility of DNMT inhibitors in switching on the immune response through viral mimicry and offers a scientifically validated and immediately accessible option that could significantly improve survival for patients with R/R NKTL.

Statistics:

  • 21 patients with R/R NKTL participated in the study.
  • 10 patients had complete remission and four had a partial response following treatment with the combination.
  • The two-year overall survival rate was 50.2%.
  • The median overall survival was significantly improved compared to the three-month benchmark for patients whose disease has progressed after anti-PD-1 treatment.
  • Preclinical mouse models show that the acquired resistance to anti-PD-1 treatment is associated with typical features of "cold" tumors.

Sources:

  • American Association for Cancer Research. "Epigenetic therapy boosted immunotherapy response in refractory natural killer/T-cell lymphoma by turning cold tumors hot."
  • Tan, J., et al. "Combination of PD-1 inhibitor and DNMT inhibitors in relapsed or refractory natural killer/T-cell lymphoma." Cancer Discovery (2017).