— UL97- and UL54-resistant CMV retinitis treated with multivirus-inform T-cell remedy
Kate Kneisel, Contributing Creator, MedPage This day
April 17, 2023
A kidney transplant recipient of their mid-30s developed novel-onset floaters in each and every eyes, per a case represent in JAMA Ophthalmology.
The patient had purchased a kidney from a deceased donor. Scientific historical previous also incorporated cytomegalovirus (CMV) colitis and CMV viremia and documented UL97 and UL54 gene mutations, reported Lauren A. Dalvin, MD, and colleagues at Mayo Clinic in Rochester, Minnesota.
The patient’s CMV viremia had previously demonstrated resistance to foscarnet and ganciclovir. Systemic immunosuppressive medicine with maribavir had been discontinued no longer too long ago in step with resistance concerns, and cidofovir and CMV immune globulin had been progressively equipped.
Scientific examination printed visible acuity of 20/25 OD and 20/20 OS. Findings on motility, visible fields, and anterior section evaluation were traditional. A dilated fundus examination confirmed “tortuous vasculature, quite lots of cotton wool spots along the arcades and periphery, and granular, hypopigmented retinal lesions without hemorrhage within the macula and temporal periphery in each and every eyes,” the case authors said.
Optical coherence tomography printed localized areas of stout-thickness retinitis. Serology confirmed CMV titers of two.24 million IU/mL, indicating viremia. Despite the patient’s known UL97 and UL54 mutations, a series of five intravitreal injections of foscarnet and ganciclovir were administered on a biweekly foundation so that you can take care of the vision-threatening lesions.
The intravitreal medicine did not make stronger the patient’s retinal pathology; if reality be told, every injection modified into followed by distress and temporarily reduced visible acuity. This in a roundabout draw led to the patient’s refusing additional intravitreal remedy.
Dalvin and colleagues diagnosed the patient with UL97– and UL54-resistant CMV retinitis.
The staff belief about quite lots of next steps. Continuing medicine with systemic cidofovir and CMV immune globulin or with intravitreal injections of foscarnet and ganciclovir were each and every like a flash dismissed as suboptimal. The patient had came upon the transient harmful effects of the latter insupportable, they explained. Moreover, “no main enchancment modified into viewed using these medications within the context of documented mutations within the UL97 and UL54 genes.”
A UL97 gene mutation contributes to ganciclovir and valganciclovir resistance, and a UL54 gene mutation is associated with resistance to ganciclovir, valganciclovir, foscarnet, and cidofovir, Dalvin and colleagues said. Given the patient’s high viral load, advantages of leflunomide would even be brief-lived, they worthy, since resistance would potentially develop soon after medicine modified into initiated.
The staff pointed to cytotoxic T lymphocytes (CTLs) as a novel remedy for CMV retinitis that is no longer responding to traditional therapies. “One of those immunotherapy, CTLs involve adoptive switch of donor T cells to present a virus-inform immune response to certain an infection,” they explained.
On this case, medicine with the multivirus-inform T-cell remedy posoleucel resulted in dramatic enhancements internal 1 month of the first infusion. Optimistic response modified into seen in retinal outcomes to boot to in CMV titers, which lowered from 2.24 million IU/mL to 14,700 IU/mL. The patient’s energetic retinitis resolved entirely, with residual scarring, and visible acuity modified into maintained at 20/20 OD and 20/25 OS.
Eight weeks after the patient’s initial diagnosis — 6 weeks after the first infusion — the patient returned for a conference-up evaluation. At that level, some vision loss had occurred. The patient’s easiest-corrected visible acuity modified into 20/70 OD and 20/60 OS.
On educate-up examination with optical coherence tomography, the workers worthy novel subretinal fluid below the fovea in each and every eyes, and a bilateral broaden in retinal thickness (factual search: 273 to 336 μm; left search: 273 to 324 μm). “CMV lesions in each and every eyes remained indolent,” Dalvin and co-authors said.
Sooner than the workers modified into in a contrivance to function additional checking out, the patient developed posttransplant lymphoproliferative dysfunction, which led to a like a flash deterioration in health space. The patient modified into transitioned to hospice care.
“The patient’s lowered vision may signify an harmful attain of CTL remedy or cidofovir, nonetheless the critically in bad health space of the patient precluded definitive diagnosis,” Dalvin’s team said.
CMV retinitis that develops in patients following an organ transplant can even be no longer easy to take care of as a result of want for long-term immunosuppression, which authors worthy needs to be accompanied by “ongoing antiviral remedy for an an increasing number of resistant virus.”
Literature is sparse concerning outcomes of CMV retinitis that has been treated with CTL remedy, Dalvin and colleagues seen. They cited one represent of exercise of CMV-inform T-cell medicine in a series of seven patients “wherein 90% of eyes executed disease dedication and 80% had stable or improved visible acuity.”
Sooner than receiving CTL remedy, revolutionary retinitis persevered in all patients despite their receiving systemic and intravitreal antiviral remedy. Of the seven patients, three had UL97 mutations and one had a UL54 mutation, the authors worthy. “Underlying immunosuppression modified into secondary to stem cell transplant in four patients, AIDS in two patients, and kidney transplant in a single patient.”
In that diminutive quantity of patients, medicine modified into neatly tolerated. None were tormented by immune recovery uveitis; there modified into one case of cystoid macular edema, and two cases of retinal detachment.
Beyond ocular concerns, CTL remedy can even be associated with harmful systemic effects, per stories in oncology patients, which believe described cytokine initiate syndrome, immune effector cell-associated neurotoxicity syndrome, and cytopenias.
Nonetheless, in distinction to the seven-patient series described above, “we used multivirus-inform T-cell remedy in wish to CMV-inform T cells,” Dalvin and workers said. “Total, CTL remedy is a promising novel remedy that requires additional investigation, ideally with potential trials, to believe in thoughts its role within the medications for CMV retinitis.”
Kate Kneisel is a contract medical journalist primarily based in Belleville, Ontario.
Dalvin reported enhance from the Leonard and Mary Lou Hoeft Occupation Pattern Award Fund in Ophthalmology Analysis and grants from the National Cancer Institute and National Middle for Advancing Translational Science.
Supply Reference: Tailor PD, et al “Blurred vision after a kidney transplant” JAMA Ophthalmol 2023; DOI: 10.1001/jamaophthalmol.2023.0707.