Anti–PD-1 Antibody Pidilizumab Plus Rituximab Shows High Activity in Relapsed Follicular Lymphoma


Key Points

  • Treatment with pidilizumab plus rituximab produced objective response in 66% of patients and complete response in 52%.
  • There were no autoimmune or treatment-related adverse events of grade 3 or 4.

Antitumor immune responses may be inhibited by immune checkpoints in the tumor microenvironment including effects of PD-1 (programmed cell death 1), a co-inhibitory receptor on tumor T cells that impairs T-cell function. In a phase II study reported in The Lancet Oncology, Westin et al assessed the effects of the anti–PD-1 antibody pidilizumab in combination with rituximab (Rituxan) in patients with relapsed follicular lymphoma. Treatment was associated with a high response rate and no autoimmune or severe treatment-related adverse events of grade 3 or 4.

Study Details

In this study, conducted at MD Anderson Cancer Center, 30 adult patients with rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies received intravenous pidilizumab at 3 mg/kg every 4 weeks for four infusions plus eight optional infusions every 4 weeks in patients with stable disease or better. Starting 17 days after the first pidilizumab infusion, patients received rituximab at 375 mg/m2 weekly for 4 weeks. 

Study patients had a median age of 61 years, and 57% were male. Twenty-three percent had intermediate risk and 33% high risk on Follicular Lymphoma International Prognostic Index (FLIPI)-1, and 50% had intermediate risk and 27% had high risk on the FLIPI-2. Patients had received a median of one previous therapy (range, 1–4) with a median time since last therapy of 24 months, and previous therapies consisted of combination chemotherapy in 70%, biologic combination in 37%, radioimmunotherapy in 7%, rituximab maintenance in 23%, and rituximab monotherapy in 3%; all patients had previously received rituximab, with a median of seven doses (range, 2–22).

Response and Progression-Free Survival

Patients received a median of 10 pidilizumab infusions (range, 1–12) and 97% received all four rituximab infusions. Median follow-up was 15.4 months. Of the 29 patients evaluable for response, 19 (66%) had objective response, including complete response in 15 (52%). Median time to response was 88 days (range, 53–392) with six patients (21%) having response at > 4 months after the first pidilizumab infusion.

Measurable tumor regression occurred in 25 patients (86%). Median progression-free survival was 18.8 months in all patients, not reached in responders, and 20.2 months in those with tumor regression. Clinical response was not significantly associated with FLIPI-1, FLIPI-2, previous therapy, number of previous rituximab doses, or duration of response to previous therapy, but progression-free survival was significantly associated with FLIPI-1 and FLIPI-2. No patients died during the study.


No autoimmune or treatment-related adverse events of grade 3 or 4 were observed and no patient had a dose interruption or discontinued therapy due to adverse events. The most common grade 1 adverse events were anemia (47%), fatigue (43%), leukopenia (37%), thrombocytopenia (27%), and dyspnea (20%), and the most common grade 2 adverse events were respiratory infection (17%), fatigue (7%), thrombocytopenia (7%), and pain (7%).

The investigators concluded, “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.”

Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

The study was supported by Cure Tech, National Institutes of Health, Leukemia and Lymphoma Society, and The University of Texas MD Anderson Cancer Center. Dr. Neelapu received research support from Cure Tech. Rinat Rotem-Yehudar, PhD, is an employee of Cure Tech.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.