Presumptive Recurrence of Intraocular Lymphoma Despite Chimeric Antigen Receptor T-Cell Therapy

Abstract

Purpose: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells.Methods: Observational case report.Results: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect.Conclusion: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Ocular adverse events following CAR‐T cell therapy: A pharmacovigilance study and systematic review

“…A total of 27 ocular AEs were documented in the reviewed cases (Figure 1). 6,[8][9][10][12][13][14][15] The most common AEs were blurred vision with 10 reports, retinal disease with 5 reports, and floaters with 4 reports (Table 2. ).…”

“…Of particular concern is an AE shared by Denton et al, Khanna et al, and Zu et al wherein their patients exhibited retinal detachment, hypothesized to be a consequence of CAR T‐cell expansion and cytokine release 8,13,15 . Three intriguing cases reported by Willier et al, Abou‐Samra et al, and Taher et al were instances of ocular recurrence after CAR‐T cell therapy, including a case of acute lymphoblastic leukemia and two of diffuse large B‐cell lymphoma 6,10,14 . It is worth mentioning that the FAERS database reported one case ocular lymphoma for tisagenlecleucel (Table 1).…”

“…Pain 2 instances of ocular recurrence after CAR-T cell therapy, including a case of acute lymphoblastic leukemia and two of diffuse large B-cell lymphoma. 6,10,14 It is worth mentioning that the FAERS database reported one case ocular lymphoma for tisagenlecleucel (Table 1). Notably, most of the cases occurred in patients on anti-CD19 CAR-T cell therapy.…”

Adverse events associated with chimeric antigen receptor T-Cell therapy in ophthalmology: a narrative review

“…Several case reports have brought attention to the recurrence of hematological malignancies within the eye following CD19 CAR-T-cell therapy, despite successful control of the central nervous system and the rest of the body 35 , 36 , 45 . It is suggested that insufficient anti-CD19 CAR-T cells may enter the eye, allowing neoplastic B cells to persist.…”