Non-human primate models are poor predictors of human immunogenicity. The industry has shifted to human-relevant ex vivo assays using whole blood or PBMCs. These tests can assess risks like complement activation upfront, enabling proactive protein engineering to improve a drug's safety profile.

TDXD is highly emetogenic. Adding low-dose olanzapine to the standard three-drug antiemetic prophylaxis regimen is a transformative strategy that significantly reduces both acute and delayed nausea, making the potent therapy much more tolerable for patients.

Due to fedratinib's significant GI side effect profile and the logistical difficulty of measuring thiamine levels, clinicians should proactively provide patients with thiamine supplements, anti-emetics, and anti-diarrheal therapies. Instructing patients to take the drug with food can also help mitigate GI toxicity.

When managing drug-induced rash, recurrence is often caused by restarting therapy before the initial rash has completely resolved. Patients may be eager to resume treatment and minimize lingering symptoms, so clinicians must explicitly educate them on the need for full resolution to prevent a cycle of recurrence.

To manage the common side effect of stomatitis from datopotamab deruxtecan (Dato-DXd), a preemptive strategy is effective. Prescribing steroid mouthwash and advising patients to use ice chips during infusion can reduce the severity and incidence of this toxicity.

The HORIZON-GEA-01 trial for zanidatumab in gastric cancer mandated prophylactic loperamide (4mg BID) for all patients. This was necessary to manage the high rates of diarrhea (up to 80% of patients), a significant GI toxicity associated with the drug's mechanism of action.

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.

While avoiding severe toxicities of older IL-2 drugs, Synthakyne's therapy causes a manageable rash. The company views this as a favorable, on-target effect, indicating the drug is successfully activating the immune system as intended, rather than as a problematic side effect.

For managing nausea from ADCs like TDXD, a three-drug prophylactic regimen (steroid, 5-HT3 antagonist, NK1 inhibitor) is recommended. For delayed nausea, continuing the 5-HT3 antagonist on days two and three is often effective before needing to add agents like olanzapine.