A phase I study of the combination of rituximab and ipilimumab in patients with relapsed/ refractory B-cell lymphoma

Joseph M. Tuscano, Emanual Maverakis, Susan Groshen, Denice Tsao-Wei, Guillaume Luxardi, Alexander A. Merleev, Anne Beaven, John F. DiPersio, Leslie Popplewell, Robert Chen, Mark Kirschbaum, Mark A. Schroeder, Edward M. Newman

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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) CD20þ 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 CD20þ 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 RþI 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 RþI demonstrated that RþI 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 RþI 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.

Original languageEnglish (US)
Pages (from-to)7004-7013
Number of pages10
JournalClinical Cancer Research
Volume25
Issue number23
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tuscano, J. M., Maverakis, E., Groshen, S., Tsao-Wei, D., Luxardi, G., Merleev, A. A., Beaven, A., DiPersio, J. F., Popplewell, L., Chen, R., Kirschbaum, M., Schroeder, M. A., & Newman, E. M. (2019). A phase I study of the combination of rituximab and ipilimumab in patients with relapsed/ refractory B-cell lymphoma. Clinical Cancer Research, 25(23), 7004-7013. https://doi.org/10.1158/1078-0432.CCR-19-0438