Outcomes with ibrutinib by line of therapy and post-ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis |
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| Authors: | Susan M O'Brien John C Byrd Peter Hillmen Steven Coutre Jennifer R Brown Paul M Barr Jacqueline C Barrientos Stephen Devereux Tadeusz Robak Nishitha M Reddy Thomas J Kipps Alessandra Tedeschi Florence Cymbalista Paolo Ghia Stephen Chang Joi Ninomoto Danelle F James Jan A Burger |
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| Institution: | 1. Department of Medicine, Division of Hematology/Oncology, University of California Irvine, Irvine, California;2. Department of Internal Medicine, Division of Hematology, The Ohio State University Medical Center, Columbus, Ohio;3. Department of Haematology, St James's University Hospital, Leeds, United Kingdom;4. Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, California;5. Department of Medicine, Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts;6. Department of Medicine, Wilmot Cancer Institute, University of Rochester, Rochester, New York;7. Department of Medicine, Division of Hematology and Medical Oncology, Hofstra Northwell School of Medicine, Hempstead, New York;8. Department of Life Sciences and Medicine, Division of Cancer Studies, Kings College Hospital, London, United Kingdom;9. Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Łódź, Poland;10. Department of Medicine, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee;11. Department of Medicine, Division of Hematology-Oncology, UC San Diego Health, Moores Cancer Center, San Diego, California;12. Department of Hematology, Azienda Ospedaliera Niguarda Cà Granda, Milan, Italy;13. Service Hematologie Biologique, Hôpital Avicenne, Université Paris 13, Bobigny, France;14. Strategic Research Program in CLL, Division of Experimental Oncology, Universitè Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy;15. Biostatistics, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California;16. Clinical Science, Pharmacyclics LLC, an AbbVie Company, Sunnyvale, California;17. Department of Leukemia, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas |
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| Abstract: | The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first-line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher-risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib-treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single-agent ibrutinib: RESONATE (PCYC-1112) in patients with R/R CLL and RESONATE-2 (PCYC-1115) in patients with treatment-naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib-treated non-del(17p) patients with CLL (136 TN and 135 R/R). Median progression-free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow-up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow-up 18 months, n = 51) and was not reached in TN patients (median follow-up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy. |
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