TY - JOUR
T1 - Ocular Outcomes after Treatment of Cytomegalovirus Retinitis Using Adoptive Immunotherapy with Cytomegalovirus-Specific Cytotoxic T Lymphocytes
AU - Gupta, Mrinali P.
AU - Koenig, Lisa R.
AU - Doubrovina, Ekaterina
AU - Hasan, Aisha
AU - Dahi, Parastoo B.
AU - O'Reilly, Richard J.
AU - Koehne, Guenther
AU - Orlin, Anton
AU - Chan, Robison V.Paul
AU - D'Amico, Donald J.
AU - Park, Susanna S.
AU - Burkholder, Bryn M.
AU - Kiss, Szilárd
N1 - Funding Information:
S.S.P.: Financial support - Allergan, Roche/NovartisS.K.: Consultant - Adverum, Alcon, Novartis, Optos, Genentech/Roche; Financial support - Allergan, Novartis, Optos, Genentech/Roche, Regeneron; Patent - Cornell University; Royalties - Atara Biotherapeutics; Equity owner - Adverum, Regenxbio, Fortress Bio E.D.: Consultant and Financial support - Atara Biotherapeutics; Royalties - Atara Biotherapeutics; Patents (pending) - SK2013-71, SK2018-122 R.J.O.: Consultant and Financial support - Atara Biotherapeutics; Royalties - Atara Biotherapeutics R.V.P.C.: Financial support - Alcon Obtained funding: N/A
Publisher Copyright:
© 2021 American Academy of Ophthalmology
PY - 2021/9
Y1 - 2021/9
N2 - Purpose: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). Design: Retrospective cohort study. Participants: Patients with active CMV retinitis evaluated at a tertiary care academic center. Methods: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). 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-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. Results: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific 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%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific 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), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. Conclusions: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.
AB - Purpose: To describe ocular outcomes in eyes with cytomegalovirus (CMV) retinitis treated with adoptive immunotherapy using systemic administration of CMV-specific cytotoxic Tlymphocytes (CMV-specific CTLs). Design: Retrospective cohort study. Participants: Patients with active CMV retinitis evaluated at a tertiary care academic center. Methods: Treatment of CMV retinitis with standard-of-care therapy (systemic or intravitreal antivirals) or CMV-specific CTLs (with or without concurrent standard-of-care therapies). 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-specific CTLs, systemic antivirals, intravitreal antivirals), resolution of CMV retinitis, any occurrence of immune recovery uveitis, cystoid macular edema, retinal detachment, or a combination thereof. Results: Seven patients (3 of whom had bilateral disease [n = 10 eyes]) were treated with CMV-specific CTLs, whereas 20 patients (6 of whom had bilateral disease [n = 26 eyes]) received standard-of-care treatment. Indications for CMV-specific 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%); patient intolerance to longstanding, frequent antiviral therapy for persistent retinitis (28.6%); or a combination thereof. Two patients (28.6%; 4 eyes [40%]) received CMV-specific CTL therapy without concurrent systemic or intravitreal antiviral therapy for active CMV retinitis, whereas 5 patients (71.4%; 6 eyes [60%]) continued to receive concurrent antiviral therapies. Resolution of CMV retinitis was achieved in 9 eyes (90%) treated with CMV-specific 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), respectively. These outcomes compared favorably with a nonrandomized cohort of eyes treated with standard-of-care therapy alone, despite potentially worse baseline characteristics. Conclusions: CMV-specific CTL therapy may represent a novel monotherapy or adjunctive therapy, or both, for CMV retinitis, especially in eyes that are resistant, refractory, or intolerant of standard-of-care antiviral therapies. More generally, adoptive cell transfer and adoptive immunotherapy may have a role in refractory CMV retinitis. Larger prospective, randomized trials are necessary.
KW - Cell therapy
KW - CMV retinitis
KW - T cells
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U2 - 10.1016/j.oret.2021.04.009
DO - 10.1016/j.oret.2021.04.009
M3 - Article
C2 - 33892135
AN - SCOPUS:85110201387
VL - 5
SP - 838
EP - 849
JO - Ophthalmology Retina
JF - Ophthalmology Retina
SN - 2468-7219
IS - 9
ER -