Stilgenbauer, Stephan, Eichhorst, Barbara, Schetelig, Johannes, Hillmen, Peter, Seymour, John F., Coutre, Steven, Jurczak, Wojciech ORCID: 0000-0003-1879-8084, Mulligan, Stephen P., Schuh, Anna, Assouline, Sarit, Wendtner, Clemens-Martin, Roberts, Andrew W., Davids, Matthew S., Bloehdorn, Johannes, Munir, Talha, Boettcher, Sebastian, Zhou, Lang, Salem, Ahmed Hamed, Desai, Monali, Chyla, Brenda, Arzt, Jennifer, Kim, Su Young, Verdugo, Maria, Gordon, Gary, Hallek, Michael and Wierda, William G. (2018). Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial. J. Clin. Oncol., 36 (19). S. 1973 - 1984. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

PurposeVenetoclax is an orally bioavailable B-cell lymphoma 2 inhibitor. US Food and Drug Administration and European Medicines Agency approval for patients with 17p deleted relapsed/refractory chronic lymphocytic leukemia [del(17p) CLL] was based on results from 107 patients. An additional 51 patients were enrolled in a safety expansion cohort. Extended analysis of all enrolled patients, including the effect of minimal residual disease (MRD) negativity on outcome, is now reported.Patients and MethodsOverall, 158 patients with relapsed/refractory or previously untreated (n = 5) del(17p) CLL received venetoclax 400 mg per day after an initial dose ramp up. Responses were based on 2008 International Workshop on Chronic Lymphocytic Leukemia criteria, with monthly physical exams and blood counts. Computed tomography scan was mandatory at week 36, after which assessment made was by clinical evaluation. Marrow biopsy was performed when complete remission was suspected. MRD was assessed by flow cytometry.ResultsPatients had a median of two prior therapies (range, zero to 10 therapies), 71% had TP53 mutation, and 48% had nodes that were 5 cm. Median time on venetoclax was 23.1 months (range, 0 to 44.2 months) and median time on study was 26.6 months (range, 0 to 44.2 months). For all patients, investigator-assessed objective response rate was 77% (122 of 158 patients; 20% complete remission) and estimated progression-free survival at 24 months was 54% (95% CI, 45% to 62%). For 16 patients who received prior kinase inhibitors, objective response rate was 63% (10 of 16 patients) and 24-month progression-free survival estimate was 50% (95% CI, 25% to 71%). By intent-to-treat analysis, 48 (30%) of 158 patients achieved MRD below the cutoff of 10(-4) in blood. Common grade 3 and 4 adverse events were hematologic and managed with supportive care and/or dose adjustments.ConclusionVenetoclax achieves durable responses and was well tolerated in patients with del(17p) CLL. A high rate of blood MRD < 10(-4) was achieved in this high-risk population.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Stilgenbauer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eichhorst, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schetelig, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillmen, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seymour, John F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coutre, StevenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jurczak, WojciechUNSPECIFIEDorcid.org/0000-0003-1879-8084UNSPECIFIED
Mulligan, Stephen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuh, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assouline, SaritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendtner, Clemens-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberts, Andrew W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davids, Matthew S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloehdorn, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Munir, TalhaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boettcher, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, LangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salem, Ahmed HamedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Desai, MonaliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chyla, BrendaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arzt, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Su YoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verdugo, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gordon, GaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wierda, William G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-180507
DOI: 10.1200/JCO.2017.76.6840
Journal or Publication Title: J. Clin. Oncol.
Volume: 36
Number: 19
Page Range: S. 1973 - 1984
Date: 2018
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BCL-2 INHIBITOR; OPEN-LABEL; MULTICENTERMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/18050

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