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Venetoclax Therapy and Attainment of Undetectable Minimal Residual Disease in CLL

By: Cordi Craig
Posted: Monday, March 16, 2020

According to John F. Seymour, MD, PhD, of the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Parkville, Australia, and colleagues, the majority of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) treated with venetoclax who achieved undetectable minimal residual disease did so within the first 24 months of treatment. The study, published in Blood Advances, found that further monotherapy after 24 months was unlikely to deepen responses. Moreover, peripheral blood and bone marrow samples for undetectable disease measurements achieved comparable outcomes.

The research team retrospectively reviewed data from 62 patients with CLL. The investigators analyzed longer-term outcomes of undetectable minimal residual disease attainment and recrudescence as well as the effect of venetoclax intensification to deepen responses.

Of the 16 patients who achieved undetectable minimal residual disease in peripheral blood samples, 13 had confirmed undetectable minimal residual disease in bone marrow samples (81%). In patients with undetectable disease in peripheral blood, outcomes such as time to disease progression, overall survival, and recrudescence were at least as favorable as those with bone marrow–undetectable disease. The median time to undetectable disease in peripheral blood was 18 months; 90% of patients achieved undetectable minimal residual disease by 24 months. After 24 months, no new cases of undetectable disease in peripheral blood were reported without intensifying treatment. A significant association between concurrent rituximab and earlier attainment of undetectable disease was reported (P = .012).

Of note, a significant association between patients with a complex karyotype and inferior undetectable disease attainment after 12 months of therapy (P = .015) was observed. Similarly, there was a trend between patients with TP53 abnormalities who achieved undetectable disease and earlier recrudescence (P = .089). The dose of venetoclax was escalated in 15 patients, 4 (27%) of whom achieved improvements in response as a result.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.



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