Unlike immunotherapy, where re-challenge after progression is dubious, there is an emerging clinical practice of re-challenging patients with the same antibody-drug conjugate (ADC), such as enfortumab vedotin (EV), after a treatment break forced by toxicity. Anecdotally, patients are showing great responses, highlighting a key area for prospective data generation.

In the EV+pembrolizumab combination, if a patient achieves an excellent response but develops prohibitive EV-related toxicities like neuropathy, a viable strategy is to discontinue EV and maintain the patient on pembrolizumab monotherapy. This can sustain the response while improving quality of life.

Real-world data suggests that using one antibody-drug conjugate (ADC) immediately after another is often ineffective. A potential strategy to overcome this resistance is to administer a different class of chemotherapy before starting the second ADC.

When combining sacituzumab govitecan (SASE) and pembrolizumab (IO), it's crucial to differentiate the cause of diarrhea. SASE-induced diarrhea is similar to standard chemotherapy, while IO-induced diarrhea often presents with bloody stools and severe abdominal cramping.

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.

For rashes caused by enfortumab vedotin (EV), dupilumab is an emerging steroid-sparing treatment. It can decrease the risk and severity of EV-related rashes, offering an alternative to corticosteroids, which some clinicians worry may blunt the efficacy of concurrent immunotherapy.

To determine if fatigue or cognitive dysfunction is caused by enzalutamide, a clinician suggests a practical approach called the "Stevens Maneuver." The patient stops the drug for two weeks. If symptoms don't improve, the cause is likely something else. If they do improve, the drug is the culprit, and it can often be resumed at a lower dose.

Despite the individual high efficacy of both BCMA-directed therapies and anti-CD38 antibodies, there is significant clinical concern about combining them. The potential for compounded immunosuppression and severe infection risk is a major barrier shaping clinical trial design and favoring sequential use over concurrent combination.

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.