After PD-1 Inhibitors Fail: Is Ipilimumab an Option for Some With Metastatic Melanoma?

By: Chris Schimpf, MSW
Posted: Friday, November 1, 2024

Second-line treatment with the CTLA-4 inhibitor ipilimumab may prove an effective therapy for patients with BRAF/NRAS wild-type melanoma without brain metastases for whom treatment with PD-1 inhibitors has failed, according to new research published in the journal Cancers. Federica De Galitiis, MD, of the Istituto Dermopatico dell’Immacolata IDI-IRCCS, Rome, and colleagues found several benefits to long-term survival among this patient population in their longitudinal, real-world study. And they stressed the need for careful clinical evaluation when prescribing this course of treatment—especially among patients with NRAS mutations and those with activating BRAF mutations who have been pretreated with BRAF and MEK inhibitors.

“In this study, we provide evidence that the presence of NRAS or BRAF V600 mutations serves as a negative prognostic indicator for patients undergoing ipilimumab monotherapy,” the researchers stated. “The data suggest that these genetic mutations are associated with poorer treatment outcomes, highlighting the need for alternative therapeutic strategies in this subset of patients.”

A total of 44 patients who received ipilimumab after their cancer failed to respond to PD-1 inhibitors between July 2017 and May 2023 were included in the single-center study. Among the participants, 28 were identified as having BRAF wild-type melanoma, 9 were identified as having BRAF-mutated melanoma, and 7 were identified as having NRAS-mutated melanoma. The investigators observed a significant difference in overall survival between patients with wild-type and BRAF- or NRAS-mutated melanomas: 23.2 months vs 5.3 and 4.59, respectively (P = .017). In multivariate analysis, they found the presence of brain metastases and BRAF or NRAS mutations were independent factors for mortality.

“Further studies are necessary to better evaluate the impact of NRAS and BRAF mutations on the response to ipilimumab in melanoma and to define the best treatment for these patients after [ipilimumab plus PD-1 inhibitor] therapy failure,” the researchers added.

Disclosure: For full disclosures of the study authors, visit mdpi.com.

Cancers