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
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.
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%).
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.
National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech, and University
of Texas MD Anderson Cancer Center.
Copyright © 2014 Elsevier Ltd. All rights reserved.