Overall survival benefit with tebentafusp in metastatic uveal melanoma
Nathan P, Hassel J, Rutkowski P, Baurain J, Butler M, IMCgp100-202 Investigators
N Engl J Med 2021, 23;385:1196-1206
Review: Currently, there is no evidence of survival benefit with systemic therapy for metastatic uveal melanoma, with a one-year overall survival rate of 50%. The bispecific protein tebentafusp (Kimmtrak) consists of an affinity-enhanced T-cell receptor which fuses to an anti-CD3 effector that directs T-cells to target HLA-A*02:01 glycoprotein 100–positive cells (Fig 1, above).
This randomised, open-label, phase 3 trial included 379 patients with previously untreated metastatic uveal melanoma who were positive for the HLA-A*02:01 allele. In total, 252 received tebentafusp, while 126 received single-agent therapy with pembrolizumab (Keytruda), ipilimumab (Yervoy), or dacarbazine (DTIC-Dome) as the control. The overall survival at one year was 73% in patients with tebentafusp, compared with 59% in controls, while progression-free survival was also better (Fig 2). Among those receiving tebentafusp, 83%, 76% and 69% reported T-cell and cytokine-mediated adverse events, including rash, pyrexia, and pruritus, respectively, with 2% discontinuing the trial. No treatment-related deaths were observed. Despite antibodies against tebentaufsp being detected in some patients, the authors did not find they affected overall survival.
Comment: Approximately 45% of Caucasians in the US and Europe carry the HLA-A*02:01-allele, with a reported prevalence of 6-22% among specific populations in New Zealand. Considering the lack of effective systemic therapy for metastatic uveal melanoma, the results of this study are encouraging, with tebentafusp resulting in improved overall survival with an acceptable safety profile.
Factors associated with good visual acuity outcomes after retinectomy in eyes with proliferative vitreoretinopathy
Israilevich R, Starr M, Mahmoudzadeh R, Salabati M, Swaminathan V, Huang D et al.
Am J Ophthalmol 2022, 240:143-148








