Menin inhibitors achieve high rates of MRD-negative remissions. However, the median duration is very short (4-6 months), suggesting current MRD assays may not adequately capture residual disease and that "MRD negativity" is not a reliable predictor of long-term benefit for this drug class.

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.

When debating immunotherapy risks, clinicians separate manageable side effects from truly life-altering events. Hypothyroidism requiring a daily pill is deemed acceptable, whereas toxicities like diabetes or myocarditis (each ~1% risk) are viewed as major concerns that heavily weigh on the risk-benefit scale for early-stage disease.

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.

Modern, highly sensitive assays often detect high rates of anti-drug antibodies (ADAs). However, the critical question for drug developers isn't the ADA incidence rate itself, but whether that immune response actually impacts drug exposure, efficacy, or overall patient outcome.

Despite significant progress in managing symptoms for autoimmune conditions, very few treatments fundamentally alter the disease's course. The major unmet needs and investment opportunities lie in therapies that can induce remission or target common underlying pathologies like fibrosis, moving beyond mere symptom relief.

Sepsis is not a monolithic condition. The failure of more than 100 immunomodulatory drug trials is likely because they treated all patients the same. The future of sepsis treatment mirrors oncology: subtyping patients based on their specific inflammatory profile to match them with a targeted therapy.

Modern critical care for sepsis only treats the consequences of the disease—organ failure, low blood pressure—with supportive measures like ventilators and IV fluids. There are zero approved therapies that actually treat the underlying root cause: the out-of-control immune response that is actively damaging the patient's body.