Some AML patients can safely come off venetoclax-based therapy after achieving remission, study suggests

Blood cancers

By Natasha Doyle

19 May 2022

Certain acute myeloid leukaemia (AML) patients could come safely off venetoclax-based therapy, Australian clinicians suggest after a study saw several cases of long-term treatment-free remission.

Their retrospective study of 29 elderly, remitted AML patients on venetoclax plus azacitidine or low-dose cytarabine found over half (7/13) of those who stopped treatment were still in remission five years later.

Additionally, patients who stopped or continued treatment had similar relapse risk (rate: 46% vs 69%), median relapse-free survival and overall survival times (59.8 vs 39.5 months, P = 0.074 and 71.3 versus 50.2 months, P = 0.15, respectively), the study read.

Although larger studies are needed, the findings may “provide some confidence that some patients may be able to see long-term treatment-free remission and not everyone needs to be on continuous therapy for the rest of their lives”, Dr Chong Chyn Chua, lead author and head of malignant haematology and acute leukaemia/MDS at Northern Health, Melbourne, told the limbic.

The revelation means some patients could shirk burdens associated with indefinite therapy, including reduced quality of life, vulnerability to treatment-related toxicities, psychosocial fatigue from prolonged therapy, health-economic costs related to hospital resource use and drug procurement, and reduced treatment options on relapse, her paper suggested.

Published in Blood Advances, the study assessed outcomes in 65-to-80-year-old AML patients in remission after at least a year (19.3 vs 28.8 months) of venetoclax-based therapy who stopped treatment or continued until disease progression.

Along with the promising relapse-free and overall survival results, it saw stopped patients achieve median 45.8 months’ (95% CI: 13.9 months to not reached) treatment-free remission.

“Factors [favouring] sustained [treatment-free remission] within the cohort included NPM1 and/or IDH2 mutation at diagnosis, complete remission without measurable residual disease, and at least 12 months of [venetoclax-based] combination therapy prior to treatment cessation,” Dr Chua and her colleagues wrote.

These mutations were seen in six of seven patients who were in treatment-free remission at data cut-off, as was complete remission without minimal residual disease.

While six off-therapy patients did relapse, half were re-treated with the initial venetoclax regimen — an option unavailable to patients who’d continued therapy — and two of those achieved a second remission.

Aside from increasing patients’ treatment options, being off-therapy put patients in better stead for a second round of therapy, Dr Chua said.

“When someone progresses on treatment, you know, they’ve had a lot of therapy. They’re already fatigued from existing therapy and it might be that they start off in a less great place for the next treatment, whereas, if someone progressed after they’ve stopped therapy for an amount of time and they’re feeling alright, they may have more reserves to take on the next line of therapies,” she said.

“The introduction of [venetoclax-based] therapy [has and] will likely reshape perceptions regarding treatment expectations among older AML populations,” her paper suggested.

“Traditionally, if someone just received low-dose cytarabine or azacitidine alone, what tends to happen is [not a lot of patients go into remission, so] they just continue until disease progression,” Dr Chua said.

Furthermore, elderly AML patients have poor prognoses and not many make it to the 12-month mark on these therapies. As they achieve remission and survive beyond the year mark on venetoclax-based therapies, however, patients are starting to ask if they can come off treatment, she said.

Often, they’ll stop due to medical reasons, such as neutropenia, ophthalmological issues, recurrent urinary tract infections, thrombocytopenia-related bleeding and renal failure, the study suggested. They also ask to stop therapy due to for quality of life factors and “wanting to reduce the burden associated with injections, monitoring and pill-taking”.

Although larger, broader, prospective studies are needed, “we conclude [based on current evidence] that a durable [treatment-free remission] is possible among a select group of patients with either NPM1 and/or IDH2 mutation who have received [venetoclax-based] therapy for ≥12 months and [minimal residual disease] negative at time of treatment cessation,” Dr Chua’s article concluded.

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