Avelumab for the Treatment of Relapsed or Refractory Extranodal Nk/T-Cell Lymphoma: an Open-Label Phase 2 Study
Avelumab is a PD-L1 targeting monoclonal antibody, with known efficacy in a variety of malignancies including Merkel cell carcinoma , transitional cell carcinoma of the bladder as well as renal cell carcinoma. Its utility in relapsed or refractory extranodal NK T-cell lymphoma was evaluated in a phase 2 clinical trial, published in December 10, 2020 of the Journal Blood. In the phase 2 clinical trial, 21 patients with relapsed or refractory extranodal natural killer cell T-cell lymphoma were treated with 10 mg/kg of avelumab. It was administered on day 1 and day 15 of 28 cycle. Complete response rate was the primary endpoint. Immunohistochemistry as well as targeted sequencing were performed prior to initiating treatment. Cytokines as well as soluble PD1, PD-L1 PDL-2 were also assessed.
The complete response rate was 24%, seen in 5 out of 21 patients. The overall response rate was 38%, 8 out of 21 patients. Although non-responders showed really progression, 5 responders are currently receiving treatment. They have maintained a response per investigators.
Most treatment-related adverse events were grade 1 or grade 2. No grade 4 adverse events were observed. Treatment responses did not correlate with mutation profiles, tumor mutational burden, serum levels of cytokines or soluble PD1 or PD-L1 or PDL 2 per investigator report. The expression of PD-L1 did correlate well with avelumab response, P = 0.001. All patients who achieved a complete response, showed high PD-L1 expression in their tumor subtyping per investigators, but based on PD-L1 expression correlating with treatment response. The authors concluded “avelumab showed single agent activity in a subset of patients with relapsed or refractory extranodal NK T-cell lymphoma. The assessment of PD-L1 expression on tumor cells might be helpful for identifying responders to avelumab.”