Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
Based on the findings of this retrospective study, some patients who receive venetoclax for relapsed CLL after prior treatment with a covalent BTKi only benefit for 2-3 years, which is shorter than expected.
Who Performed the Research and Where Was it Presented:
Dr. Paul Hampel from the Mayo Clinic and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
The treatment landscape for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has changed dramatically over the last 15 years. While chemoimmunotherapy used to be the standard of care, the majority of patients now receive covalent BTK inhibitors (BTKi), such as ibrutinib, acalabrutinib, or zanubrutinib, as their first treatment. The BCL2 inhibitor venetoclax is often used as a second-line therapy. Venetoclax was developed around the same time as first-generation BTKi, so the patients in the original trials had previously been treated with chemoimmunotherapy but not with covalent BTK inhibitors since they were very new.
In the MURANO trial, which demonstrated the efficacy of venetoclax plus rituximab in relapsed / refractory CLL, the median progression-free survival was 57 months (5 years) in all patients and 37 months (3 years) in high-risk patients with deletion 17p. However, more recent studies of real-world patient data looking at venetoclax-based treatments for relapsed / refractory CLL have seen median progression-free survival times of between two and three years, much shorter than what was seen in the MURANO trial. The patients in these studies tend to have received both chemoimmunotherapy and covalent BTKi, so they are heavily pretreated. The objective of this study was to look at the outcomes of patients receiving second-line venetoclax-based treatments for relapsed CLL after previously receiving first-line treatment with a covalent BTKi.
Methods and Participants:
This was a retrospective study of patients who received venetoclax for relapsed CLL after prior treatment with a covalent BTKi at Mayo Clinic and eight centers in France. Patients who received prior chemotherapy were excluded.
Results:
- 85 patients were included who received venetoclax monotherapy (15%), venetoclax + rituximab (53%), or venetoclax + obinutuzumab (32%).
- Thirty-nine patients (46%) had stopped their previous BTKi due to disease progression. In contrast, 54% of patients had received BTKi treatment but discontinued for reasons other than disease progression (usually intolerance).
- For patients whose disease did not progress on BTKi, the median time to the subsequent therapy or death was 6.5 years.
- For patients whose disease had progressed on BTKi, the median time to the next therapy or death was 2.5 years.
- Among patients whose disease progressed on BTKi, the median duration of BTKi therapy was 4 years, which is much shorter than expected.
Conclusions:
Based on the findings of this retrospective study, some patients who receive venetoclax for relapsed CLL after prior treatment with a covalent BTKi only benefit for 2-3 years, which is shorter than expected. Those who did not progress on the prior BTKi enjoyed four more years of benefit from subsequent venetoclax treatment compared to those who had progressed on a BTKi. Because this is a small cohort of patients who only derived benefits from covalent BTKi therapy for a relatively short time (median of 4 years rather than the expected 6 to 9 years), there might be something particularly high-risk about these patients that is contributing to the short duration of benefit for second-line venetoclax-based therapy. There is more to unpack here, and it also shows that there is still a need for better therapies since not all patients derive the same benefits from a given therapy.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Outcomes with Venetoclax-Based Treatment in Patients with Covalent Bruton Tyrosine Kinase Inhibitor (cBTKi)-Treated, Chemotherapy-Naïve Chronic Lymphocytic Leukemia (CLL): An International Retrospective Study
