How would you apply the results of CheckMate 204 in an asymptomatic patient with 10-20 metastatic brain lesions on dual immunotherapy for melanoma?

The results of CheckMate 204 showed that systemic therapy with both nivolumab and ipilimumab has clinically meaningful efficacy in patients with asymptomatic, untreated melanoma metastases to the brain. In this phase 2 study, however, only 22% of the patients had 3 or more lesions. Nevertheless, intracranial responses were observed in more than half the patients treated (57%) and were somewhat durable (the 6-month and 9-month rates of progression-free survival were 64.2% and 59.5%, respectively, for intracranial disease).

For a patient with 10-20 lesions, asymptomatic, one could start with Ipi-Nivo infusions and monitor the patient clinically and with brain MRIs carefully every 3 months, and start treating the lesions that have progressed in...

In asymptomatic patients receiving effective systemic immunotherapy, local therapies (surgery or radiation) may be deferred unless there is evidence of progression or new symptoms in patients with multiple brain metastases. (Kattenhøj et al., PMID 39061198; Vogelbaum et al., PMID 34932393)

Evidence of progression can be determined by modified RECIST or radiographic-only RANO-BM criteria. mRECIST is more inclusive for small lesions and is based solely on imaging, while RANO-BM incorporates clinical factors (e.g., steroid use/ neuro symptoms) and traditionally uses a 10 mm threshold. Both are reliable for response assessment in melanoma brain metastases when harmonized for lesion size and radiographic-only evaluation. Outcomes for patients wit...

I start immunotherapy and try to get Dex weaned quickly. Typically, we tend to combine immunotherapy with concurrent GKRS and have had good outcomes. We also check BRAF status, so we have TKIs as backup since BRAF inhibitors cross the BBB in the event of failure of IO and GKRS.