Send to

Choose Destination
Clin Cancer Res. 2019 Sep 3. doi: 10.1158/1078-0432.CCR-19-0438. [Epub ahead of print]

A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma.

Author information

UC Davis Comprehensive Cancer Center, Sacramento, California.
Veterans Administration Northern California Healthcare System, Sacramento, California.
Department of Dermatology, UC Davis, Sacramento, California.
Biostatistics Core, University of Southern California/Norris Cancer Center, Los Angeles, California.
University of North Carolina Comprehensive Cancer Center, Chapel Hill, North Carolina.
Washington University School of Medicine, St. Louis, Missouri.
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California, USA.
Taiho Oncology, Princeton, New Jersey.
Division of Molecular Pharmacology, Department of Medical Oncology, City of Hope, Duarte, California, USA.



Based on the potential for ipilimumab (I) to augment T-cell activation, we hypothesize that ipilimumab would augment the efficacy of rituximab (R) in patients with relapsed/refractory (R/R) CD20+ non-Hodgkin's lymphoma (NHL). This phase I study aimed to identify a recommended phase 2 dose, document toxicities, and preliminarily assess efficacy and potential predictive biomarkers.


Thirty-three patients with R/R CD20+ B-cell lymphoma received R at 375 mg/m2 weekly for 4 weeks and I at 3 mg/kg on day 1 and every 3 weeks for four doses. Responding patients went on to maintenance with each agent given every 12 weeks. To facilitate correlative analysis, the expansion phase randomized patients to simultaneous R+I versus R with I delayed 2 weeks.


Toxicity was manageable; no dose-limiting toxicity was observed at the doses studied. When considering the entire cohort, efficacy was modest, with an objective response rate (ORR) of 24% and median progression-free survival (PFS) of 2.6 months. However, in follicular lymphoma patients, the ORR was 58% with a median PFS of 5.6 months. The randomized comparison of R with R+I demonstrated that R+I resulted in more effective B-cell depletion (BCD). Both B-cell depletion and the ratio of CD45RA- regulatory T cell (Treg) to Treg were associated with response at all time points.


The combination of R+I has manageable toxicity and encouraging efficacy in R/R follicular lymphoma. The ratio of CD45RA- Tregs to total Tregs, and peripheral BCD should be studied further as potential predictors of response.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center