Dr Sullivan on Pseudoprogression as a Potential Explanation for Outcomes With Tebentafusp in Uveal Melanoma

Source: OncLive, April 2023

Ryan J. Sullivan, MD, associate professor, medicine, Harvard Medical School; associate professor, hematology/oncology, Massachusetts General Hospital, explains the prolongation of survival with tebentafusp-tebn (Kimmtrak) despite apparent initial radiographic tumor progression in patients with uveal melanoma.

According to previous research, increased circulating tumor DNA (ctDNA) levels are generally reflective of a higher tumor burden, Sullivan begins. However, patients receiving immunotherapy agents, such as immune checkpoint inhibitors, can often experience pseudoprogression, he explains. In this phenomenon, an initial increase in tumor size is observed at the same time that ctDNA levels decrease. Due to the apparent radiographic progression, this phenomenon often leads to premature treatment discontinuation. Later radiographic scans will eventually align with the reduction in tumor burden, Sullivan adds.

A study of ctDNA levels in patients with metastatic uveal melanoma receiving the bispecific T-cell engager tebentafusp showed that 88% of patients with previously untreated disease had reduced ctDNA levels after treatment with this agent. Patients with a higher degree of ctDNA reduction were shown to experience improved overall survival (OS), Sullivan continues. However, these patients did show a low overall response rate of 10% according to RECIST v1.1 criteria. Notably, tebentafusp is associated with OS benefit but not response benefit, Sullivan notes. These findings show that some patients benefit from continued treatment despite apparent disease progression.