T-Cell–Engaging Bispecific Therapies and Ocular Inflammation Emerging Phenotypes, Immunologic Mechanisms, and Clinical Management

T-cell–engaging bispecific therapies are increasingly used in hematologic and solid malignancies. This narrative review aims to summarize reported ocular adverse events associated with these therapies, critically evaluate the strength of available evidence, and propose a practical approach to their recognition and management. A narrative review of published case reports, clinical series, clinical trial safety findings, pharmacovigilance analyses, and U.S. Food and Drug Administration (FDA) safety communications was conducted to identify ocular adverse events associated with T-cell–engaging bispecific therapies. Available evidence was evaluated with emphasis on clinical presentation, potential causality, differential diagnosis, and management considerations. Reported ocular events include uveitis and sclerouveitis during teclistamab therapy, orbital inflammation during xaluritamig treatment, and orbital tumor pseudoprogression during elranatamab treatment. A mosunetuzumab pharmacovigilance analysis identified three uveitis reports among 1,154 primary-suspect reports, although these data do not permit estimation of patient incidence. Uveitis was also reported in a clinical trial evaluating mosunetuzumab combined with polatuzumab vedotin. FDA surveillance has identified uveitis as a potential safety signal for teclistamab and elranatamab. Important differential diagnoses include infection, malignant infiltration, cytokine-associated edema, and neurologic causes of visual symptoms. Ocular inflammatory events have been documented during T-cell–engaging bispecific therapy; however, their incidence, causality, and underlying mechanisms remain uncertain. Current evidence supports clinical vigilance but does not establish a class-wide ocular toxicity syndrome. Prompt ophthalmic evaluation of new ocular symptoms and multidisciplinary collaboration between oncologists and ophthalmologists are recommended as reasonable clinical approaches. Standardized monitoring protocols, corticosteroid treatment strategies, and criteria for treatment rechallenge require further prospective investigation. Teclistamab-associated uveitis and sclerouveitis are documented clinical observations; limited reports do not establish a class effect or incidence.Orbital manifestations may represent true immune-mediated orbital inflammation or tumor pseudoprogression; the distinction can change oncologic management.Visual complaints may arise from the eye, orbit, optic nerve, central nervous system (CNS), systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, or malignancy.Corticosteroid responsiveness and treatment continuation or resumption in selected reports are observations, not evidence of a universally safe management strategy.Evidence is insufficient to establish routine screening requirements; symptom-triggered referral is a proposed clinical approach, with individualized baseline assessment. Teclistamab-associated uveitis and sclerouveitis are documented clinical observations; limited reports do not establish a class effect or incidence. Orbital manifestations may represent true immune-mediated orbital inflammation or tumor pseudoprogression; the distinction can change oncologic management. Visual complaints may arise from the eye, orbit, optic nerve, central nervous system (CNS), systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, or malignancy. Corticosteroid responsiveness and treatment continuation or resumption in selected reports are observations, not evidence of a universally safe management strategy. Evidence is insufficient to establish routine screening requirements; symptom-triggered referral is a proposed clinical approach, with individualized baseline assessment.

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Publication Details

Journal
Figshare
Published
2026-11-02
DOI
https://doi.org/10.6084/m9.figshare.34888788
Primary Topic
Drug-Induced Ocular Toxicity
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article

T-Cell–Engaging Bispecific Therapies and Ocular Inflammation Emerging Phenotypes, Immunologic Mechanisms, and Clinical Management

Abdulrahman Alhadlag
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Figshare
Drug-Induced Ocular Toxicity
article

T-Cell–Engaging Bispecific Therapies and Ocular Inflammation Emerging Phenotypes, Immunologic Mechanisms, and Clinical Management

Abdulrahman Alhadlag
article en

Abstract

T-cell–engaging bispecific therapies are increasingly used in hematologic and solid malignancies. This narrative review aims to summarize reported ocular adverse events associated with these therapies, critically evaluate the strength of available evidence, and propose a practical approach to their recognition and management. A narrative review of published case reports, clinical series, clinical trial safety findings, pharmacovigilance analyses, and U.S. Food and Drug Administration (FDA) safety communications was conducted to identify ocular adverse events associated with T-cell–engaging bispecific therapies. Available evidence was evaluated with emphasis on clinical presentation, potential causality, differential diagnosis, and management considerations. Reported ocular events include uveitis and sclerouveitis during teclistamab therapy, orbital inflammation during xaluritamig treatment, and orbital tumor pseudoprogression during elranatamab treatment. A mosunetuzumab pharmacovigilance analysis identified three uveitis reports among 1,154 primary-suspect reports, although these data do not permit estimation of patient incidence. Uveitis was also reported in a clinical trial evaluating mosunetuzumab combined with polatuzumab vedotin. FDA surveillance has identified uveitis as a potential safety signal for teclistamab and elranatamab. Important differential diagnoses include infection, malignant infiltration, cytokine-associated edema, and neurologic causes of visual symptoms. Ocular inflammatory events have been documented during T-cell–engaging bispecific therapy; however, their incidence, causality, and underlying mechanisms remain uncertain. Current evidence supports clinical vigilance but does not establish a class-wide ocular toxicity syndrome. Prompt ophthalmic evaluation of new ocular symptoms and multidisciplinary collaboration between oncologists and ophthalmologists are recommended as reasonable clinical approaches. Standardized monitoring protocols, corticosteroid treatment strategies, and criteria for treatment rechallenge require further prospective investigation. Teclistamab-associated uveitis and sclerouveitis are documented clinical observations; limited reports do not establish a class effect or incidence.Orbital manifestations may represent true immune-mediated orbital inflammation or tumor pseudoprogression; the distinction can change oncologic management.Visual complaints may arise from the eye, orbit, optic nerve, central nervous system (CNS), systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, or malignancy.Corticosteroid responsiveness and treatment continuation or resumption in selected reports are observations, not evidence of a universally safe management strategy.Evidence is insufficient to establish routine screening requirements; symptom-triggered referral is a proposed clinical approach, with individualized baseline assessment. Teclistamab-associated uveitis and sclerouveitis are documented clinical observations; limited reports do not establish a class effect or incidence. Orbital manifestations may represent true immune-mediated orbital inflammation or tumor pseudoprogression; the distinction can change oncologic management. Visual complaints may arise from the eye, orbit, optic nerve, central nervous system (CNS), systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infection, or malignancy. Corticosteroid responsiveness and treatment continuation or resumption in selected reports are observations, not evidence of a universally safe management strategy. Evidence is insufficient to establish routine screening requirements; symptom-triggered referral is a proposed clinical approach, with individualized baseline assessment.

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Drug-Induced Ocular Toxicity
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