Coordinated Pembrolizumab and High Dose IL-2 (5-in-a-Row Schedule) for Therapy of Metastatic Clear Cell Renal Cancer.

Autor: Chatzkel J; Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, FL., Schell MJ; H. Lee Moffitt Cancer Center, Department of Biostatistics and Bioinformatics, Tampa, FL., Chahoud J; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL; University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL., Zhang J; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL; University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL., Jain R; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL; University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL., Swank J; H. Lee Moffitt Cancer Center, Department of Pharmacy, Tampa, FL., Ludlow S; H. Lee Moffitt Cancer Center, Department of Pharmacy, Tampa, FL., Lombardi K; H. Lee Moffitt Cancer Center, Department of Pharmacy, Tampa, FL., Lucas Y; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL., Croft C; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL., Rembisz J; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL., Jameel G; H. Lee Moffitt Cancer Center, Department of Genitourinary Oncology, Tampa, FL., Fishman M; University of South Florida Morsani College of Medicine, Department of Internal Medicine, Tampa, FL; Tampa General Hospital Cancer Institute, Genitourinary Oncology, Tampa, FL. Electronic address: fishman@usf.edu.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2022 Jun; Vol. 20 (3), pp. 252-259. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1016/j.clgc.2022.01.010
Abstrakt: Introduction: The ligation of the interleukin-2 (IL-2) receptor and immune checkpoint blockade may each alter lymphocytes, thereby inducing regression in various cancers. Single agent objective response rates of 14% to 25% have been reported for usual schedule 14-dose-in-a-row IL-2 therapy of metastatic clear cell renal cancer (ccRCC), with a notable subset of responses being durable. Pembrolizumab yielded a 33% response rate in patients with metastatic ccRCC.
Patients and Methods: This study addressed the safety and feasibility of the combination of IL-2 and pembrolizumab in the treatment of metastatic ccRCC. Subjects were treated with four 9-week blocks of therapy, receiving pembrolizumab every 3 weeks in all blocks and receiving 4 courses of 5-planned-doses high dose IL-2 in each of blocks 2 and 3. Safety was monitored by a Pocock boundary of study suspension and re-evaluation if exceeding a 15% dose limiting toxicity rate at α = 0.05. The Simon 2-stage design tested for an alternative hypothesis response rate of at least a 45% vs. a null hypothesis rate of less than 20%, with α = 0.10 and 90% power RESULTS: No accrual suspension for safety was triggered. The objective response rate was 70% (19/27, 95% CI: 0.50-0.86). Nine patients responded after pembrolizumab alone and ten responded after the addition of IL-2. At a minimum follow-up of 23 months, 9 of the responding patients had no disease progression requiring additional treatment.
Conclusion: The combination of 5-planned-dose-schedule high dose IL-2 and pembrolizumab is feasible, with a high response rate, justifying further exploration of this dual immune treatment of metastatic ccRCC.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: