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Dr. Chaitra Ujjani, of the Seattle Cancer Care Alliance (SCCA), is a rising star in the CLL world.
At the ASH 2019 meeting, in Orlando, Florida in December, we discussed the important Veneto-STOP trial that examines the best time to stop venetoclax when treating chronic lymphocytic leukemia.
- Venetoclax’s FDA approval has broadened, to where now it is approved for use in all CLL patients in the USA at any point in their treatment journey.
- The duration of therapy has also changed as the indications widened. When it was first approved, it was envisioned as a medication taken indefinitely until disease progression or intolerance. This is the model that has proven so successful for CLL patients with ibrutinib, acalabrutinib, idelalisib, and duvelisib.
- Now we have protocols where we stop venetoclax at various arbitrary times including at 12, 18 and 24 months with little data to suggest the best duration of therapy.
- We do know that if the CLL is undetectable (U-MRD) or undetectable minimal disease when therapy is stopped, it is possible to have a very durable remission. U-MRD predicts for good outcomes.
- The testing for U-MRD in this trial will include clonoSEQ, a next generation sequencing test that can detect CLL down to one in a million cells. This is the same test used after my CAR-T trial that I explain in my blog post.
- Sadly, the opposite is also true about MRD status. Patients who do have measurable disease when treatment ends tend to progress more quickly and may have a more difficult time controlling the disease. Fortunately, there is recent evidence that ibrutinib is often effective post venetoclax.
- What all this suggests is that the duration of treatment should be individualized based on the patient’s depth of response and not on some arbitrary number of therapy cycles, and this trial sets out to see if that is indeed the case.
- The trial will study patients taking venetoclax with or without a monoclonal antibody, such as rituximab or obinutuzumab.
- After at least 6 months, patients will start to be checked for U-MRD in the peripheral blood (not the bone marrow) and if they test negative twice, at least one month apart, they will be offered the option to stop the venetoclax.
- They will be continued to be monitored and encouraged to retry venetoclax should they relapse.
- The trial will be studying how long patients can go without treatment after stopping venetoclax and how well will they respond to a second course of venetoclax-based therapy if they relapse. It will also assess their quality of life pre and post treatment.
This is an important trial that will answer questions about the best duration of therapy and the ability to retreat with venetoclax. It will also provide patients access to one or maybe two medications, in which cost should be covered by the trial.
I like how it will use the patient’s depth of response as the guiding light to determine when to stop therapy. That just makes sense. I also approve of how it continues to follow the patient after the first course of therapy into the drug-free remission period and into a second treatment if the need arises.
I also like how it may minimize exposure to drug. Patients can stop the venetoclax when the disease burden is so low that it can’t be measured rather than continuing to treat when no treatment may be needed.
What the study does not do is look at ways to intensify therapy should the patient not be one of the lucky one who achieves U-MRD, or when to stop therapy if it seems likely that U-MRD is never going to be reached.
It also does not examine the patient’s preference for fixed duration versus indefinite therapy. Fortunately, the CLL SOCIETY is planning to do just such a study.
The trial is not open at the time of writing this review, but we will update the post when it does open.
Here is my interview with Dr. Ujjani.
Here is the link to the ASH 2019 abstract: Veneto-STOP Study: Sequential Assessment of Minimal Residual Disease By Next Generation Sequencing to Optimize Outcomes and Minimize Exposure in Venetoclax-Treated CLL Patients
We are all in this together.
Dr. Brian Koffman, a well-known retired doctor, educator, and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the Executive Vice President and Chief Medical Officer of the CLL Society Inc.
Originally published in The CLL Society Tribune Q1 2020.