Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Abstract

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.

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. ).…”

“…Notably, the literature revealed a prevalent AE, blurred vision, documented in over half of cases featuring ocular AEs, a presentation that is absent in FAERS reports 9 . 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 .…”

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

“…112 Thus, while the incidence of CMV viremia may be underestimated, the clinical relevance of these events remains unclear with most patients improving, even without preemptive antiviral therapy. Cases of CMV end-organ disease have been described, 36,38,111,[113][114][115][116] but are overall rare considering the widespread use of CAR-T-cell therapy in the United States and globally. However, few studies have evaluated CMV viremia in a systematic fashion in this population and the clinical relevance of asymptomatic reactivation remains unknown.…”