The failure of an adjuvant trial for the TKI pazopanib was likely caused by a protocol change that reduced the dose to manage transaminitis. While well-intentioned to improve tolerability and adherence, the lower dose was sub-therapeutic. This serves as a critical lesson that managing side effects by compromising dose can nullify a drug's potential efficacy.

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.

BTK inhibitors function as highly potent antiplatelet agents, an 'on-target' effect. Many surgeons are unaware, leading to significant post-operative bleeding if the drug isn't stopped. Patients must be educated to inform their surgical teams and advocate for themselves.

Due to significant ocular toxicity affecting most patients, the approved starting dose for belantumab is likely not optimal long-term. Effective management requires clinicians to proactively hold, delay, and reduce doses at the first sign of side effects, meaning real-world application will differ from the initial protocol.

For myelofibrosis patients with profound splenomegaly but only moderate thrombocytopenia (platelets 50k-100k), fedratinib may be the best frontline option. It is arguably the most potent JAK inhibitor for spleen reduction and is approved for use in patients with platelet counts as low as 50,000.

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.

For myelofibrosis patients with both anemia and splenomegaly, a practical approach is to start with ruxolitinib for its superior symptom control. If the subsequent anemia is not well-tolerated, switching to momelotinib allows for a more informed, personalized decision based on the patient's experience with both agents.

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.

Recurrent non-melanoma skin cancers in patients on ruxolitinib may be attributable to its JAK1 inhibition. In such cases, a viable strategy is to switch the patient to a more JAK2-selective inhibitor, such as pacritinib or fedratinib, to potentially mitigate this specific side effect while maintaining disease control.