ASH 2021 | HOVON 141/VISION: MRD guided time-limited treatment in CLL
Carsten Niemann, MD, PhD, Copenhagen University Hospital, Copenhagen, Denmark, presents results from the prospective, randomized Phase II HOVON-141/VISION trial (NCT03226301), which assessed time-limited venetoclax and ibrutinib for patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Patients reaching undetectable minimal residual disease (MRD) after venetoclax and ibrutinib either received maintenance ibrutinib or stopped treatment, and all patients who failed to reach MRD status received maintenance ibrutinib. MRD guided time-limited treatment was proven to be beneficial, where the primary endpoint of progression-free survival (PFS) was met. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
So the VISION/HOVON 141 trial, is our aim at defining time-defined treatment in relapsed/refractory CLL setting for patients based on ibrutinib and venetoclax. Essentially we took inspiration from the CML disease and how the tyrosine kinase inhibitors were introduced. And afterwards shown also to be… could be stopped safely in patients who achieved a molecular remission. So what we did here was actually to follow patients based on MRD, minimal residual disease measurements...
So the VISION/HOVON 141 trial, is our aim at defining time-defined treatment in relapsed/refractory CLL setting for patients based on ibrutinib and venetoclax. Essentially we took inspiration from the CML disease and how the tyrosine kinase inhibitors were introduced. And afterwards shown also to be… could be stopped safely in patients who achieved a molecular remission. So what we did here was actually to follow patients based on MRD, minimal residual disease measurements. And for patients who achieved an undetectable MRD status in peripheral blood and bone marrow at cycle 15, they were randomized between continuing ibrutinib monotherapy or observation. And for patients in the observation arm, we followed them every three months, tested whether they had still undetectable MRD, or if they became MRD detectable, above 10 to minus third level, we would retest them in a month. And if they increased above 10 to second level, we would reinitiate treatment.
That’s not considered failure, if a patient had to reinitiate treatment, as long as we could prevent clinical progression. So [inaudible 00:01:18] testing, if we could have the time defined treatment, but MRD guided, follow the patients and make sure that we could safely capture any signs of subclinical progression and reinitiate treatment. And I believe the study was a great success. We had a 98% progression-free survival, one year after studying therapy, that’s 27 months after initiating treatment for this patient population.
We have predefined that it should just be above 75%. Obviously we need longer follow up to see what would be the real value of this. But I think this is the first step towards a practice changing outcome in a clinical trial, for how to define MRD-guided therapy and stop and start of therapy for CLL in relapsed/refractory setting.
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