The Bottom Line:
This study shows that patients with relapsed/refractory chronic lymphocytic leukemia (CLL) recovered immune function after fixed-duration treatment with venetoclax plus rituximab. This suggests that if we can bring CLL under control with fixed-duration targeted therapy combinations, patients are more likely to recover their immune function and experience fewer infections in the long term.
Who Performed the Research and Where Was it Presented:
Dr. Arnon Kater from Cancer Center Amsterdam and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
The MURANO trial was one of the first clinical trials where a targeted therapy was given for a fixed duration rather than as a continuous therapy. Because targeted therapies were relatively new at the time, almost none of the patients in the trial had received previous treatment with targeted therapy. CLL and small lymphocytic lymphoma (SLL) cause dysregulation of the immune system, and therapies such as venetoclax and anti-CD20 antibodies like rituximab are known to reduce immune function further. However, little is known about how fixed-duration treatments impact long-term immune function after treatment has stopped.
In this video, Dr. Javier Pinilla, Senior Member and Head of the Lymphoma Section at Moffitt Cancer Center interviewed Dr. Arnon Kater, a hematologist at Amsterdam UMC in the Netherlands. They discussed a recent analysis of the long-term immune changes in patients with relapsed/refractory CLL after treatment with fixed-duration venetoclax plus rituximab.
Methods and Participants:
The MURANO trial was a phase 3 clinical trial comparing fixed-duration venetoclax + rituximab with chemoimmunotherapy (bendamustine + rituximab) in patients with relapsed/refractory CLL. This analysis looked at long-term immune changes post-treatment in patients who completed the full venetoclax + rituximab course without progressive disease.
Results:
- Immunoglobulins (IgG, IgA, IgM) are antibodies made by B cells.
- IgG levels decreased from baseline to the end of treatment, which is expected because rituximab kills normal and cancerous B cells, and venetoclax can suppress immunity in several ways.
- After treatment ended, immunoglobulin levels recovered over time.
- Two years after the end of treatment, IgG levels were similar to what they had been at baseline.
- IgA levels increased after treatment ended.
- IgM levels were reduced during treatment with venetoclax + rituximab but increased back to baseline levels after treatment ended.
- The number of B cells was reduced during treatment and started to recover about one year after the end of treatment.
- Treatment with venetoclax + rituximab normalized the number of T cells and natural killer cells.
- Infection rates were low and higher during treatment than after treatment.
Conclusions:
This study shows that patients with CLL experienced immune recovery following fixed-duration treatment with venetoclax plus rituximab. This suggests that if we can bring CLL / SLL under control with fixed-duration targeted therapy combinations, patients are more likely to recover their immune function and experience fewer infections in the long term.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Long-Term Host Immune Changes Following Treatment with Venetoclax Plus Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia
Take care of yourself first.
Ann Liu, PhD
