- 作者：Jason R Westin ; Fuliang Chu ; Min Zhang ; Luis E Fayad ; Larry W Kwak ; Nathan Fowler ; Jorge Romaguera ; Fredrick Hagemeister ; Michelle Fanale ; Felipe Samaniego ; Lei Feng ; Veerabhadran Balad ; ayuthapani ; Zhiqiang Wang ; Wencai Ma ; Yanli Gao ; Michael Wallace ; Luis M Vence ; Laszlo Radvanyi ; Tariq Muzzafar ; Rinat Rotem-Yehudar ; R Eric Davis ; et al.
- 刊名：Lancet Oncology
- 出版年：January, 2014
- 年：2014
- 卷：15
- 期：1
- 页码：69-77
- 全文大小：445 K
Summary
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 (鈮?8 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/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. This trial is registered with , number .
Findings
We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median follow-up was 15路4 months (IQR 10路1-21路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.