Medically reviewed by Dr. Brian Koffman
The Bottom Line:
In a cohort of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were treated with Bruton tyrosine kinase inhibitors (BTKi), adverse events were a primary reason for discontinuing therapy. With the introduction of acalabrutinib and zanubrutinib, which have fewer side effects, the hope is that fewer patients will need to stop treatment due to adverse events and that they will be able to stay on BTKi therapy for longer.
Who Performed the Research and Where Was it Presented:
Dr. Kevin Lin from Brigham and Women’s Hospital, Dana-Farber Cancer Institute, and colleagues presented the results at the American Society for Hematology Annual Meeting 2022.
Background:
Bruton tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of CLL / SLL and ushered in a new era of targeted therapies, which target specific molecules that cancer cells need to survive and spread. Unfortunately, previous studies had reported on outcomes for BTKi discontinuation in cohorts of patients from an era when the majority were relapsed or refractory to multiple prior lines of chemoimmunotherapy. However, now patients with CLL / SLL receive BTKi earlier in their treatment course as a first- or second-line therapy.
In this video, Dr. Deborah Stephens, Director of the CLL and Lymphoma program at the University of Utah Huntsman Cancer Institute, interviewed Dr. Kevin Lin, a Brigham and Women’s Hospital resident. They discussed a new study that looked at BTKi discontinuation in a contemporary cohort of patients with CLL / SLL.
Methods and Participants:
This study was a retrospective chart review of adult CLL / SLL patients at Dana-Farber Cancer Institute treated with at least one covalent BTKi and discontinued treatment.
Results:
- Sixty-seven patients who started a BTKi between 2011 and 2019 were included in the analysis.
- BTKi treatments were given as the first line (27%), second line (33%), third line (18%), fourth line (12%), and fifth or greater line (9%) of therapy.
- Most patients (88%) were treated with ibrutinib, and 12% were treated with acalabrutinib.
- Reasons for discontinuing BTKi therapy included adverse events (55%), disease progression (35%), and Richter transformation (5%).
- The most common adverse events leading to discontinuation were abnormal heart rhythm (atrial fibrillation, 22%) and bleeding events (14%), known risks of ibrutinib.
- The prevalence of these side effects would be expected to decrease over time as doctors and patients shift to using acalabrutinib and zanubrutinib, which have fewer side effects than ibrutinib.
- Following their last BTKi treatment, 54% of patients received subsequent therapies, most of which were regimens containing venetoclax.
- Richter transformation, which is when CLL transforms into a more aggressive diffuse large B cell lymphoma, occurred in 5% of patients.
- This is lower than expected based on other studies, which typically see 9-10% of patients experience Richter transformation, but the reasons for this are unclear.
Conclusions:
Adverse events are a significant reason that patients discontinue BTKi therapy. With the introduction of acalabrutinib and zanubrutinib, the hope is that fewer patients will need to stop treatment due to side effects and that they will be able to stay on BTKi therapy for longer.
Links and Resources:
Watch the interview on the abstract here:
Clink the link to read the actual ASH abstract: Patient Characteristics, Treatment Patterns, and Outcomes Following Covalent Btki Discontinuation in a Contemporary Cohort of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL / SLL) Patients.
Take care of yourself first.
Ann Liu, PhD
