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Published on: November 26, 2018
Long-term outcomes for patients with chronic lymphocytic leukemia who discontinue ibrutinib
Preetesh Jain1, Philip A Thompson1, Michael Keating1
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Insights
Long-term outcomes for chronic lymphocytic leukemia (CLL) patients discontinuing ibrutinib show survival varies by reason. Disease transformation yielded poor outcomes, while progression offered better survival, highlighting the need for effective salvage therapies.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Ibrutinib, a Bruton tyrosine kinase inhibitor, is an approved treatment for chronic lymphocytic leukemia (CLL) in both frontline and relapsed/refractory settings.
- Previous studies indicated poor outcomes for patients discontinuing ibrutinib, but long-term survival data were lacking.
Purpose of the Study:
- To analyze the long-term outcomes of patients with chronic lymphocytic leukemia (CLL) after discontinuing ibrutinib therapy.
- To investigate the association between the reason for ibrutinib discontinuation and patient survival.
Main Methods:
- Retrospective analysis of data from 320 patients treated with ibrutinib on clinical studies between 2010 and 2015.
- Focus on the subset of patients (90/320) who discontinued ibrutinib, examining reasons for cessation and subsequent survival.
Main Results:
- After a median follow-up of 38 months, 40% of patients who discontinued ibrutinib remained alive.
- Major reasons for discontinuation included intolerance (32%), miscellaneous causes (31%), progression (21%), and Richter transformation (RT) (10%).
- Median survival varied significantly by discontinuation reason: 33 months for intolerance, 11 months for miscellaneous, 16 months for progression, and 2 months for RT. Among those with progressive CLL, 42% responded to subsequent therapies.
Conclusions:
- Ibrutinib discontinuation is a significant event in CLL treatment, with outcomes heavily influenced by the reason for cessation.
- Patients experiencing Richter transformation had particularly poor prognoses, while those with progressive CLL showed better survival compared to disease transformation.
- Developing effective salvage strategies for CLL patients progressing on ibrutinib is crucial for improving long-term outcomes.
Background:
Ibrutinib is a Bruton tyrosine kinase inhibitor and is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) in frontline and relapsed/refractory settings. The authors previously reported poor outcomes for patients who discontinued ibrutinib; however, long-term outcomes were not reported.
Methods:
Data from 320 patients who received ibrutinib on clinical studies between 2010 and 2015 at The University of Texas MD Anderson Cancer Center were retrospectively analyzed.
Results:
Long-term outcomes among patients with CLL after they discontinued ibrutinib were analyzed. Ninety of 320 patients (28%) who were treated on ibrutinib-based regimens discontinued ibrutinib. Of these, 80 had relapsed/refractory disease, and 10 were treatment-naive. The median time to discontinuation was 15 months (range, 1.2-54 months). After a median follow-up of 38 months after starting ibrutinib, 40 patients (44%) remained alive. Major reasons for ibrutinib discontinuation were intolerance (n = 29; 32%), miscellaneous (n = 28; 31%), progression (n = 19; 21%), and Richter transformation (RT) (n = 9; 10%). The median survival according to the reason for discontinuation was 33 months for ibrutinib intolerance, 11 months for miscellaneous causes, 16 months for progressive CLL, and 2 months for RT. Among the 19 patients who had progressive CLL, 42% responded to subsequent therapy.
Conclusions:
Ibrutinib discontinuation was observed during therapy. Patients with CLL who had disease transformation had especially poor outcomes, whereas those who developed progressive disease during ibrutinib therapy had a median survival of <1.5 years. Survival was associated with the reason for discontinuation; patients who had progressive CLL had better survival compared with those who had disease transformation. Effective salvage strategies for patients with CLL who progress on ibrutinib therapy is of critical importance. Cancer 2017;123:2268-2273. © 2017 American Cancer Society.
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