BACKGROUND: 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. We did this phase 2 
trial to investigate the activity of pidilizumab, a humanised anti-PD1 
monoclonal antibody, with rituximab in patients with relapsed follicular 
lymphoma.
METHODS: We did this open-label, non-randomised trial at the University of Texas 
MD Anderson Cancer Center (Houston, TX, USA). Adult (≥18 years) 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/m(2) 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. 
This trial is registered with ClinicalTrials.gov, number NCT00904722.
FINDINGS: We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median 
follow-up was 15.4 months (IQR 10.1-21.0). 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 (five 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%).
INTERPRETATION: The combination of pidilizumab plus rituximab is well tolerated 
and active in patients with relapsed follicular lymphoma. Our results suggest 
that immune checkpoint blockade is worthy of further study in follicular 
lymphoma.
FUNDING: National Institutes of Health, Leukemia and Lymphoma Society, Cure 
Tech, and University of Texas MD Anderson Cancer Center.