TY - JOUR
T1 - A phase I study of the combination of rituximab and ipilimumab in patients with relapsed/ refractory B-cell lymphoma
AU - Tuscano, Joseph M.
AU - Maverakis, Emanual
AU - Groshen, Susan
AU - Tsao-Wei, Denice
AU - Luxardi, Guillaume
AU - Merleev, Alexander A.
AU - Beaven, Anne
AU - DiPersio, John F.
AU - Popplewell, Leslie
AU - Chen, Robert
AU - Kirschbaum, Mark
AU - Schroeder, Mark A.
AU - Newman, Edward M.
N1 - Funding Information:
J.M. Tuscano recieved research funding from Celgene, Novartis, Spectrum, and Takada. J.M. Tuscano received honoraria from Celgene, Amgen, and Seattle Genetics. E. Maverakis received research support from Roche, Pfizer, Amgen, and Abbvie. The family of A. Beaven has equity in GSK. M.A. Schroeder has consultancy with Amgen, Incyte, Sanofi, Flatron, and from Merk and Takada. No potential conflicts of interest were disclosed by the other authors.
Funding Information:
This work was supported in part by NIH awards U01CA062505, UM1CA186717, P30CA033572, and P30CA093373, and the Biostatistics Core of P30CA014089. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. E. Maverakis was supported by an early career award from the Burroughs Wellcome Fund and an NIH Director's New Innovator Award (DP2OD008752).
Publisher Copyright:
2019 American Association for Cancer Research.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85075958355&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-0438
DO - 10.1158/1078-0432.CCR-19-0438
M3 - Article
C2 - 31481504
AN - SCOPUS:85075958355
SN - 1078-0432
VL - 25
SP - 7004
EP - 7013
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 23
ER -