Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
Patients with CLL treated with ibrutinib have a 9-year overall survival rate similar to that of the age-matched general population, irrespective of high-risk features.
Who Performed the Research and Where Was it Presented:
Dr. Jan Burger from MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
When patients receive a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), one of the first questions that comes to mind is, how long am I going to live? The answer to that question has changed significantly in the past decade as the standard of care has shifted from chemoimmunotherapy to targeted therapies such as Bruton tyrosine kinase inhibitors (BTKi), significantly improving patient outcomes. Ibrutinib was the first BTKi developed, so researchers now have very long follow-up data on patients from some of those early clinical trials. They compared overall survival in patients with CLL treated with ibrutinib with data from the general US population matched for age.
Methods and Participants:
This analysis used data from two phase 3 clinical trials in which patients received ibrutinib alone or ibrutinib plus rituximab as their first therapy. Overall survival probabilities were compared with age-matched US general population data from the Centers for Disease Control.
Results:
- This study included 490 patients in total, with a median age of 61 years at the time of randomization to treatment.
- The 9-year overall survival rate in CLL patients treated with ibrutinib (81%) was nearly identical to those of the age-matched general population (82%).
- In high-risk patients with CLL (deletion 11q, deletion 17p, TP53 mutation, unmutated IGHV) treated with ibrutinib, the 9-year overall survival rate was 80%, which was similar to the age-matched general population (83%)
- From the time of initial diagnosis, the 15-year overall survival rates for ibrutinib-treated patients were 78% and 72% for the general population.
- 43% of patients discontinued ibrutinib due to side effects, and 21% discontinued due to progressive disease.
Conclusions:
In the past, patients with CLL would be expected to have shorter life spans because of their cancer, even with treatment with chemoimmunotherapy. Patients with high-risk features, in particular, were known to have much shorter remissions with chemoimmunotherapy. With the introduction of targeted therapies like ibrutinib, patients with CLL now have a life expectancy that is similar to the general population and largely eliminated the shorter overall survival that was previously seen in patients with high-risk features. In other words, regardless of age or high-risk features, first-line treatment with ibrutinib provides CLL patients similar to a matched cohort without CLL. This is remarkable progress.
One of the remaining challenges with using BTKi, like ibrutinib, is the high discontinuation rate due to side effects. Second-generation BTKi, such as acalabrutinib and zanubrutinib, have improved safety profiles and will hopefully be easier for patients to tolerate. BTKi are also used in time-limited combination therapies, which give patients a reprieve from treatment. Despite these challenges, BTKi remains a very effective therapy for CLL with clear survival benefits.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Treatment with First-Line Ibrutinib Improves Overall Survival in Patients with Chronic Lymphocytic Leukemia (CLL) and High-Risk Genomic Features to Rates Approximating an Age-Matched US Population: Pooled Analysis of Phase 3 Trials with 10 Years of Follow-up
