• Stephan Stilgenbauer, Barbara Eichhorst, Johannes Schetelig, Peter Hillmen, John F Seymour, Steven Coutre, Wojciech Jurczak, Stephen P Mulligan, Anna Schuh, Sarit Assouline, Clemens-Martin Wendtner, Andrew W Roberts, Matthew S Davids, Johannes Bloehdorn, Talha Munir, Sebastian Böttcher, Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, Gary Gordon, Michael Hallek, and William G Wierda.
• Stephan Stilgenbauer and Johannes Bloehdorn, Ulm University, Ulm; Stephan Stilgenbauer, Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg; Barbara Eichhorst and Michael Hallek, Universitätsklinikum Köln, Köln; Johannes Schetelig, University Hospital, Technische Universität Dresden, Dresden; Clemens-Martin Wendtner, Klinikum Schwabing, Munich; Sebastian Böttcher, University Hospital of Schleswig-Holstein, Kiel, Germany; Peter Hillmen and Talha Munir, St James's University Hospital, Leeds; Anna Schuh, University of Oxford; Anna Schuh, Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom; John F. Seymour, Peter MacCallum Cancer Centre; John F. Seymour, University of Melbourne; Andrew W. Roberts, Royal Melbourne Hospital, Parkville, Victoria; Stephen P. Mulligan, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Steven Coutre, Stanford University Medical Center, Stanford, CA; Wojciech Jurczak, Jagiellonian University, Kraków, Poland; Sarit Assouline, McGill University, Montreal, Quebec, Canada; Matthew S. Davids, Dana-Farber Cancer Institute, Boston, MA; Lang Zhou, Ahmed Hamed Salem, Monali Desai, Brenda Chyla, Jennifer Arzt, Su Young Kim, Maria Verdugo, and Gary Gordon, AbbVie, North Chicago, IL; Ahmed Hamed Salem, Ain Shams University, Cairo, Egypt; and William G. Wierda, The University of Texas MD Anderson Cancer Center, Houston, TX.
• J. Clin. Oncol. 2018 Jul 1; 36 (19): 1973-1980.

AbstractPurpose Venetoclax 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 Methods Overall, 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. Results Patients 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. Conclusion Venetoclax 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.

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