Endogenous or iatrogenic antitumour immune responses can improve the course of follicular lymphoma, but might be diminished by immune checkpoints in the tumour microenvironment. These checkpoints might include effects of programmed cell death 1 ( PD1 ), a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells.
A phase 2 trial has investigated the activity of Pidilizumab, a humanised anti-PD1 monoclonal antibody, with Rituximab ( MabThera, Rituxan ) in patients with relapsed follicular lymphoma.
Researchers did this open-label, non-randomised trial at the University of Texas MD Anderson Cancer Center ( Houston, TX, USA ).
Adult ( 18 years or more ) patients with Rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies were eligible.
Pidilizumab was administered at 3 mg/kg intravenously every 4 weeks for four infusions, plus eight optional infusions every 4 weeks for patients with stable disease or better.
Starting 17 days after the first infusion of Pidilizumab, Rituximab was given at 375 mg/m2 intravenously weekly for 4 weeks.
The primary endpoint was the proportion of patients who achieved an objective response ( complete response plus partial response according to Revised Response Criteria for Malignant Lymphoma ).
Analysis was by intention to treat.
Researchers enrolled 32 patients during the period 2010-2012. Median follow-up was 15.4 months.
The combination of Pidilizumab and Rituximab was well tolerated, with no autoimmune or treatment-related adverse events of grade 3 or 4.
The most common adverse events of grade 1 were anaemia ( 14 patients ) and fatigue ( 13 patients ), and the most common adverse event of grade 2 was respiratory infection ( 5 patients ).
Of the 29 patients evaluable for activity, 19 ( 66% ) achieved an objective response: complete responses were noted in 15 ( 52% ) patients and partial responses in four ( 14% ).
In conclusion, the combination of Pidilizumab plus Rituximab was well tolerated and active in patients with relapsed follicular lymphoma.
The results suggest that immune checkpoint blockade is worthy of further study in follicular lymphoma. ( Xagena )
Westin JR et al, The Lancet Oncology 2014; 15: 69-77