Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series

The CheckMate 743 trial established nivolumab and ipilimumab as the standard first-line treatment for unresectable pleural mesothelioma. However, optimal management following disease progression after a durable response to dual immunotherapy remains unclear. We report two cases of patients with pleural mesothelioma (epithelioid subtype) initially treated with nivolumab-ipilimumab, achieving prolonged disease control. Both patients experienced disease progression several years after treatment discontinuation and were subsequently retreated with nivolumab-ipilimumab on regulatory approval. In both cases, retreatment resulted in stable disease for at least 12 months. However, immune-related toxicities occurred, with one patient developing recurrent colitis and the other experiencing nephrotic syndrome, ultimately leading to treatment discontinuation. These cases suggest that retreatment with dual immunotherapy may be a viable strategy for selected patients with previous durable responses, although the risk of immune-related toxicity remains significant. Given the lack of prospective data, further research is needed to determine whether rechallenge with nivolumab-ipilimumab offers superior outcomes compared with chemotherapy or best supportive care in this setting. Rechallenging patients with pleural mesothelioma with nivolumab-ipilimumab after a durable response is feasible but associated with immune-related toxicity.