The FLAG-IDA plus venetoclax regimen achieves very high MRD-negative remission rates. However, its similar efficacy in both frontline and first salvage settings suggests it might be more strategically deployed as a salvage therapy, avoiding its high toxicity in all patients upfront.
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After observing deep, MRD-negative responses at their starting dose, Colonia Therapeutics unconventionally tested a lower dose level. This counter-intuitive strategy aims to identify the minimum effective dose, which is crucial for maximizing the safety profile (the therapeutic window) and improving commercial viability through lower manufacturing costs.
Despite impressive data supporting HMA/Venetoclax, its application in younger, fit patients must be cautious. The pivotal VIALE-A trial excluded key subgroups like FLT3, core binding factor, and certain NPM1 patients, for whom intensive chemotherapy remains the standard.
Corvus Pharmaceuticals is already planning frontline combination trials for its T-cell lymphoma drug. The drug's favorable safety profile is the critical enabler, allowing it to be paired with chemotherapy and used as a long-term maintenance therapy to prolong remissions—a strategy unavailable to more toxic drugs.
An expert argues the path to curing metastatic cancer may mirror pediatric ALL's history: combining all highly active drugs upfront. Instead of sequencing treatments after failure, the focus should be on powerful initial regimens that eradicate cancer, even if it means higher initial toxicity.
The IDH1 inhibitor olutasidenib demonstrates a much longer duration of response than ivosidenib. One hypothesis is that olutasidenib's weaker affinity for wild-type IDH1 makes it a more selective inhibitor of the mutant protein, leading to more durable disease control.
To combat the significant myelosuppression from the standard 28-day venetoclax cycle in AML, many clinicians are adopting a strategy of performing a bone marrow biopsy around day 21 and pausing the drug if blast clearance is achieved to allow for hematologic recovery.
Initial studies combining menin inhibitors with venetoclax/azacitidine showed high remission rates but also high mortality. Using each agent at its full, 28-day dose caused severe, fatal myelosuppression, forcing protocol amendments to shorten drug exposure to manage toxicity.
While Tumor Lysis Syndrome with venetoclax in newly diagnosed AML is rare, clinicians should be aware of a different, insidious complication: a potentially severe Cytokine Release Syndrome (CRS)-like reaction, particularly in patients with monocytic leukemia.
The NCI-supported MyeloMatch trial is pioneering a new standard for AML diagnostics, providing comprehensive genomic, FISH, and karyotype analysis within 72 hours. This rapid turnaround allows for immediate risk stratification and assignment to appropriate clinical trials.
TP53-mutated AML carries an extremely poor prognosis, significantly worse than other adverse-risk subtypes. When TP53 patients are excluded from analyses, the survival gap between the remaining adverse-risk and intermediate-risk patients narrows considerably, clarifying risk stratification.