THE ADDITION of venetoclax to intensive chemotherapy in young, fit patients with newly diagnosed acute myeloid leukaemia (AML) has been labelled safe and feasible by a small singe-centre study. The current research brings forward exciting evidence to the ongoing search for improvement to the regimen, aimed at extending long-term survival where previously the standard of care has employed cytarabine and anthracyclines.
This study included 50 patients, where 94% of participants had a composite complete response to the regimen and 82% an undetectable measurable residual disease. Aiming to further optimise frontline therapy, venetoclax was applied in fit patients with AML, aged 65 and under, with a median age of 48. Participants received cladribine and cytarabine intravenously on Days 1–5 and idarubicin on Days 1–3. On Days 2–8, 400mg venetoclax was given with each course. Those with a known FLT3-ITD or FLT3-TKD mutation received midostaurin or gilteritinib.
Of the 50 participants, 42 had a complete response and 5 had complete with incomplete blood count recovery. Two patients did not respond, and a third died during induction therapy, although considered unrelated to treatment. The estimated 12-month event-free survival rate was 68%.
The researchers acknowledge limitations to their study; that the evidence is based on a single-centre, single-arm study with no comparator or control groups. However, it nonetheless provides a “basis for future randomised comparisons to help confirm the benefit in increasing long-term overall survival,” according to Tapan Kadia, MD Anderson Cancer Center, Houston, Texas, USA, one of the lead investigators.
Prachi Jain and Alice Mims, Ohio State University, Columbus, Ohio, USA, provided insight on the next steps in this research, agreeing that a randomised, multicentre study is required to fully evaluate the benefits of venetoclax added to intensive chemotherapy. They also raised the question of which therapies will be optimal in combination: “The question remains whether more intensive chemotherapy is needed as the backbone for venetoclax or whether a comparison of hypomethylating agents plus venetoclax would show similar results in regards to outcomes, including MRD negativity, with less toxicity and potentially better quality of life.”