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In the past decade, the number of treatment options available to patients with chronic lymphocytic leukemia (CLL) has greatly expanded. Numerous drugs are now available, but clinicians are still trying to understand a number of questions about the best way to use them including:
- When should they be used?
- What order should they be used in?
- When should combinations be used?
- How long should they be used?
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Dr. Brian Koffman interviewed Dr. Paolo Ghia, Director of the Strategic Research Program on CLL at Università Vita-Salute San Raffaele in Milan, Italy. They discussed results from a clinical trial which individually tailored treatment plans based on measurable/minimal residual disease (MRD) status.
- This is a phase 2 clinical trial testing MRD-driven treatment intensification with venetoclax and ibrutinib in patients with relapsed/refractory CLL.
- Patients started with venetoclax treatment for 1 year.
- MRD status was evaluated in the both the peripheral blood and bone marrow using flow cytometry (detection limit of 1 in 10,000 cells).
- In order to stop treatment, patients had to have undetectable MRD in both the peripheral blood and bone marrow.
- After the first year of treatment with venetoclax, patients with undetectable MRD stopped treatment. Patients with detectable MRD added ibrutinib and continued with treatment for another year.
- After the second year of treatment, patients with undetectable MRD stopped treatment. Patients with detectable MRD continued on ibrutinib alone to manage their disease.
- 38 patients with relapsed/refractory CLL were enrolled in the trial. About 60% had previously been treated with chemoimmunotherapy. Most had high-risk genetic features such as del(17p), TP53 mutations, or unmutated IGHV.
- Approximately 45% of patients were able to achieve undetectable MRD with venetoclax alone.
- Of the patients who continued on with venetoclax + ibrutinib, 80% were able to achieve undetectable MRD.
- In total, 87% of patients achieved undetectable MRD
- Only 3 patients did not achieve undetectable MRD and continued on ibrutinib.
- Neutropenia (decreased white blood cell counts) was observed, but this did not lead to increased infections.
- Diarrhea was also observed, and this is a known side effect of combining venetoclax with ibrutinib.
- While limited-duration treatments are of great interest right now, they may not work for everyone. Some patients may actually need continuous treatment to manage their disease.
Researchers are increasingly looking at more potent combinations of drugs in the hopes of producing deeper remissions. However, this study showed that a more conservative approach in conjunction with MRD testing can also be very effective. For some patients, limited-duration monotherapy was enough, while others needed combination therapy or even continuous treatment. MRD testing is a powerful tool, and MRD-guided treatment seems to be the way of the future.
Please enjoy this brief interview with Dr. Ghia from the virtual ASH meeting which was held December 2020.
You can read the actual abstract here: Minimal Residual Disease-Driven Treatment Intensification By Sequential Addition of Ibrutinib to Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: Results of the Monotherapy and Combination Phases of the Improve Study.
Take care of yourself first.
Ann Liu, PhD