Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
In this study, venetoclax ramp-up without prior anti-CD20 antibody therapy was safe for patients with CLL with a low rate of tumor lysis syndrome.
Who Performed the Research and Where Was it Presented:
Dr. Christopher Pleyer and colleagues from the National Heart, Lung, and Blood Institute of the National Institutes of Health presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Venetoclax is a very potent drug, and it kills chronic lymphocytic leukemia (CLL) cells so quickly that it can cause tumor lysis syndrome (TLS). In TLS, cancer cells die so quickly that the body has no time to clear out the debris. This leads to sudden changes in electrolyte levels, which can lead to kidney failure, heart arrhythmias, and seizures. Because of this, the conventional wisdom has been that we need to reduce the amount of cancer present before starting patients on venetoclax. One way to do this is to start patients on anti-CD20 monoclonal antibody therapy (mAb), such as rituximab or obinutuzumab, prior to initiating venetoclax. However, because venetoclax is much better at killing CLL cells than anti-CD20 antibodies, researchers wanted to determine whether venetoclax can be safely started without an anti-CD20 mAb lead-in.
Methods and Participants:
This study included patients with treatment-naïve or relapsed / refractory CLL who needed active treatment. Venetoclax was started with a 5-week ramp-up and continued for approximately one year for treatment-naïve patients or two years for patients with relapsed / refractory CLL. Patients had the option to add anti-CD20 mAb therapy after the 5-week venetoclax ramp-up.
Results:
- A total of 50 patients were enrolled in the study, including 24 treatment-naïve patients and 26 patients with relapsed / refractory CLL.
- Among patients with relapsed / refractory CLL, 92% had previously been treated with a BTK inhibitor.
- Only two patients (4%) developed tumor lysis syndrome. Both patients had relapsed / refractory disease and were medium-risk for TLS.
- These patients had changes in lab values indicative of tumor lysis syndrome, but they did not experience any clinical symptoms.
- Other patients with bulky disease or who were considered high-risk did not experience tumor lysis syndrome, but the caveat is that this was a small number of patients.
- Almost all patients received anti-CD20 mAb therapy after venetoclax ramp-up (100% of treatment-naïve, 89% of relapsed / refractory).
- The 2-year progression-free survival was 92% for treatment-naïve patients and 83% for relapsed / refractory patients. These rates are similar to those seen in phase 3 clinical trials.
Conclusions:
Venetoclax ramp-up without prior anti-CD20 mAb therapy was safe for patients with CLL with a low rate of tumor lysis syndrome. This study reassures physicians and their patients that there is room for flexibility in how they sequence therapies. This flexibility is attractive because prior research has suggested that anti-CD20 monoclonal antibody therapy (mAb), such as rituximab or obinutuzumab, works better with a lower tumor burden. That is due to the improved “drug to target” ratio.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Activity and Safety of Venetoclax without Anti-CD20 Lead-in Therapy in Treatment Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia
