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 - 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 -