While CELMoDs frequently cause neutropenia, this effect is most pronounced in early cycles and manageable with growth factors. This contrasts sharply with the persistent, quality-of-life-impairing non-hematologic side effects of lenalidomide, such as rash and severe fatigue. This trade-off results in a significantly better long-term tolerability profile for patients.

A multi-center study revealed patients receiving glucarpidase were inherently sicker with more severe kidney injury. This selection bias means simple comparisons are misleading; only after adjusting for these factors does the drug's significant benefit in kidney recovery become clear.

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.

With highly active agents yielding 30% complete response rates, the immediate goal should be to cure more patients by exploring potent combinations upfront. While sequencing minimizes toxicity, an ambitious combination strategy, such as ADC doublets, offers the best chance to eradicate disease and should be prioritized in clinical trials.

Clinical evidence suggests a critical 48- to 60-hour window for administering glucarpidase post-methotrexate infusion. Once irreversible organ injury occurs, the drug's benefit is significantly reduced. This narrow timeframe underscores the need for rapid diagnosis and intervention.

The 'safety first' mandate in drug development is flexible. For cancers like leukemia with high cure rates, highly aggressive therapies with severe side effects are deemed acceptable. The risk-benefit calculation shifts dramatically when a cure, not just management, is the goal.

The mtxpk.org pharmacokinetic tool visualizes a patient's predicted versus actual methotrexate clearance. A significant deviation from the ideal curve provides objective, data-driven evidence for delayed clearance, helping clinicians justify the early use of costly glucarpidase to hospital administrators.

The term "functional cure" is misleading and hinders progress. With one-third of heavily pretreated patients in the Cartitude 1 trial remaining disease-free for five years without maintenance, the data supports the classical definition of a "cure" used in other cancers. This semantic shift is crucial for advancing the field.

Clinicians can avoid treatment delays and unnecessary fluid administration by having patients start sodium bicarbonate before hospital admission. This proactive strategy ensures the patient's urine is appropriately alkalized, allowing high-dose methotrexate to be administered safely and on schedule.