Outcomes with ibrutinib by line of therapy and post‐ibrutinib discontinuation in patients with chronic lymphocytic leukemia: Phase 3 analysis

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 thi...

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Bibliographic Details
Published in:American journal of hematology 2019-05, Vol.94 (5), p.554-562
Main Authors: O'Brien, Susan M., Byrd, John C., Hillmen, Peter, Coutre, Steven, Brown, Jennifer R., Barr, Paul M., Barrientos, Jacqueline C., Devereux, Stephen, Robak, Tadeusz, Reddy, Nishitha M., Kipps, Thomas J., Tedeschi, Alessandra, Cymbalista, Florence, Ghia, Paolo, Chang, Stephen, Ninomoto, Joi, James, Danelle F., Burger, Jan A.
Format: Article
Language:English
Subjects:
Adult
Aged
Chronic lymphocytic leukemia
Data processing
Disease-Free Survival
Female
Follow-Up Studies
Hematology
Humans
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - mortality
Life Sciences
Lymphatic leukemia
Male
Middle Aged
Patients
Pyrazoles - administration & dosage
Pyrazoles - adverse effects
Pyrimidines - administration & dosage
Pyrimidines - adverse effects
Survival
Survival Rate
Targeted cancer therapy
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Summary: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.
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.25436