MARIPOSA-2 Toxicity Management: Amivantamab Delay vs Dose Reduction

The discussion turned to practical experiences with the MARIPOSA-2 regimen, especially regarding the use of amivantamab in combination with chemotherapy in the second-line setting. One key insight was that although amivantamab can be a challenging drug due to its adverse effect profile, it tends to be better tolerated when given alongside chemotherapy. Premedication with steroids such as dexamethasone can help mitigate infusion reactions, and dosing every 3 weeks is more manageable compared with biweekly schedules. Dose reductions have also proven helpful for toxicity management, particularly because amivantamab’s long half-life means adverse effects build gradually and can be difficult to reverse quickly. Starting with a lower dose in patients at risk may prevent severe toxicities from developing.

Regarding dose adjustments, the panel emphasized balancing dose reductions and treatment interruptions. Interruptions can help when toxicities become intolerable, but because symptoms often linger due to the drug’s pharmacokinetics, a longer hold (several weeks) is usually needed for meaningful improvement. After a pause, resuming at a lower dose tends to be the preferred approach. Some patients may choose not to restart therapy after significant toxicities, but overall, clinicians try to avoid permanent discontinuation when possible by using proactive dose modifications and supportive care measures. Preventative strategies such as skin care, prophylaxis for blood clots, and close monitoring play a critical role in helping patients stay on treatment.

Finally, the group discussed the importance of being mindful of infusion reactions that can recur after prolonged treatment interruptions. For example, if therapy is held for more than 4 weeks, the risk of reactions upon restarting rises, so pharmacists and care teams should plan premedications carefully and consider splitting doses. Despite these challenges, infusion reactions are usually manageable and should not deter temporary treatment holds when necessary. Overall, the approach to managing MARIPOSA-2 adverse effects involves careful dose adjustments, vigilant monitoring, and a patient-centered mindset to maintain therapy and quality of life.