Traditional age cutoffs for AML therapy are becoming obsolete. A comprehensive fitness assessment, not just chronological age, should guide treatment, as some guidelines now classify patients as young as 55 as "older adults," a surprising shift for many clinicians.
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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.
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.
The modern practice of waiting for detailed diagnostic and genetic information before starting AML therapy provides a crucial, previously unavailable window of time for clinicians to conduct thorough fitness and geriatric assessments on their older patients.
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.
When a highly effective therapy like EV Pembro was approved for 'cisplatin ineligible' patients, the definition of 'ineligible' became very elastic in practice. This demonstrates that when a new treatment is seen as transformative, clinicians find ways to qualify patients, putting pressure on established guidelines.
While quizartinib's benefit is less pronounced in AML patients over 60, a specific genomic signature—the co-occurrence of FLT3-ITD, NPM1, and DNMT3A mutations—identifies a subset of older patients who derive a significant survival benefit, challenging age-based treatment decisions.
Beyond tackling fatal diseases to increase lifespan, a new wave of biotech innovation focuses on "health span"—the period of life lived in high quality. This includes developing treatments for conditions often dismissed as aging, such as frailty, vision loss, and hearing decline, aiming to improve wellbeing in later decades.
Orca Bio's initial trials focused on younger patients who can withstand intense chemotherapy. Now, they are strategically expanding their addressable market by demonstrating Orca T's effectiveness with reduced-intensity conditioning. This makes the curative therapy safer and accessible to a larger population of older or frailer patients.
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.
By auditing the "noise" or corruption in a cell's epigenetic settings, scientists can determine a biological age. This "epigenetic clock" is a better indicator of true health than birth date, revealing that a 40-year-old could have the biology of a 30-year-old.
