Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576. (22nd January 2022)

• Record Type: Journal Article
• Authors: Castro, Januario E.; Lengerke-Diaz, Paula A.; Velez Lujan, Juliana; Choi, Michael Y.; Moreno-Cortes, Eider F.; Forero, Jose V.; Garcia-Robledo, Juan Esteban; Jacobs, Chaja; McCarthy, Colin; Heinen, Alaina; Amaya-Chanaga, Carlos I.; Kipps, Thomas J.
• Other Names: Matutes Estella M. Academic Editor.
• Is Part Of: Advances in hematology. Volume 2022(2022)
• Publication Date: 2022-01-22
• Subjects: Hematology -- Periodicals; Hematologic Diseases; Hematology; Hematology; Periodicals; Periodicals; 616.15
• DOI: 10.1155/2022/4450824
• Languages: English
• ISSNs: 1687-9104

Abstract

Abstract : Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768 ).