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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

1
UC Davis Comprehensive Cancer Center, Sacramento, California. jtuscano@ucdavis.edu.
2
Veterans Administration Northern California Healthcare System, Sacramento, California.
3
Department of Dermatology, UC Davis, Sacramento, California.
4
Biostatistics Core, University of Southern California/Norris Cancer Center, Los Angeles, California.
5
University of North Carolina Comprehensive Cancer Center, Chapel Hill, North Carolina.
6
Washington University School of Medicine, St. Louis, Missouri.
7
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California, USA.
8
Taiho Oncology, Princeton, New Jersey.
9
Division of Molecular Pharmacology, Department of Medical Oncology, City of Hope, Duarte, California, USA.

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

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