Ocular outcomes after treatment of cytomegalovirus (CMV) retinitis using adoptive immunotherapy with CMV-specific cytotoxic T-lymphocytes.

Abstract Objective To describe ocular outcomes in eyes with CMV retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic T-lymphocytes (CMV-CTLs) Design Retrospective cohort study Subjects Patients with active CMV retinitis evaluated at a tertiary care academic center Methods Treatment of CMV retinitis with either CMV-CTLs or standard-of-care therapy with systemic and/or intravitreal antiviral therapy. Main Outcome Measures The electronic medical record was reviewed to determine baseline characteristics, treatment course, and ocular outcomes, including: best-corrected visual acuity (BCVA), treatments administered (CMV-CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, and/or retinal detachment. Results Seven patients (of which 3 had bilateral disease; i.e. 10 eyes) were treated with CMV-CTLs, while 20 patients (of which 6 had bilateral disease; ie. 26 eyes) were treated with standard-of-care. Indications for CMV-CTL therapy included: persistent or progressive CMV retinitis (71.4% of patients), CMV UL54 or UL97 antiviral resistance mutations (42.9%), side effects or toxicity from antiviral agents (57.1%), and/or patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%). Two patients (28.6%, 4 eyes (40%))) received CMV-CTL therapy without concurrent systemic and/or intravitreal antiviral therapy for active CMV retinitis, while 5 patients (71.4%; 6 eyes (60%)) continued to receive concurrent antiviral therapies. Resolution of CMV-retinitis was achieved in 9 (90%) eyes treated with CMV-CTLs, with BCVA stabilizing (4 eyes, 40%) or improving (4 eyes, 40%) in 80% of eyes over an average follow-up of 33.4 months. Rates of immune recovery uveitis, new onset cystoid macular edema, and retinal detachment were 0%, 10% (1 eye), and 20% (2 eyes). These outcomes compared favorably to a non-randomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. Conclusion CMV-CTL therapy may represent a novel monotherapy and/or adjunctive therapy for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, there may be a role for adoptive cell transfer and adoptive immunotherapy in refractory CMV retinitis. Larger, prospective, randomized trials are necessary.