Manifestations of Teclistamab-Associated Uveitis

Teclistamab (Janssen, Beerse, Belgium), a novel bispecific antibody for relapsed or refractory multiple myeloma (RRMM) works by binding B-cell maturation antigen (BCMA) and CD3 on T cells, activating the T cells to destroy the myeloma cells expressing BCMA [1]. Teclistamab has shown remarkable efficacy in RRMM. It is approved by the FDA for adult patients who have received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD 38 monoclonal antibody [1]. Teclistamab is associated with adverse events, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and an increased risk of infections [1]. Recently, Liu et al. [2] reported a single case of unilateral sclerouveitis with hypopyon occurring within days of initiating teclistamab.

Here, we present two cases of acute anterior uveitis associated with teclistamab therapy occurring at different time points after treatment initiation. Both cases were successfully managed with topical corticosteroids, and infectious or autoimmune etiologies were ruled out. These cases highlight the need for vigilance in recognizing potential ocular toxicities of novel therapies, emphasizing the relevance of early detection and management.

In this manuscript, we present two distinct presentations of uveitis associated with teclistamab therapy. As a novel medication for RRMM, teclistamab has rapidly gained clinical relevance. To date, only one published report has described a case of teclistamab-associated uveitis, suggesting that such events may be underrecognized [2]. Notably, no ocular adverse events were reported in the clinical trials evaluating teclistamab, including the pivotal MajesTEC-1 study, highlighting the rarity of these findings [1]. As teclistamab use becomes more widespread, identifying and documenting these rare adverse events is essential to guide timely diagnosis and management.

Case 1 shares similarities with the previously reported case by Liu et al. [2], with both patients developing acute anterior uveitis shortly after starting teclistamab, suggesting a potential pattern of early inflammatory reaction to the drug. However, unlike Liu et al.’s case, which involved unilateral uveitis with hypopyon, our case presented bilaterally, with differing severity between the eyes. The right eye exhibited more pronounced symptoms, including a fibrin plaque in the anterior chamber, while no hypopyon was observed. The patient responded robustly to topical corticosteroids, with complete resolution of uveitis and the fibrin plaque within two weeks.

Conversely, Case 2 presented with delayed uveitis, developing seven months after teclistamab initiation. The patient exhibited anterior and intermediate uveitis with persistent vitreous involvement. This delay may indicate cumulative immune dysregulation, contributing to a more severe presentation. Further studies are needed to evaluate whether the timing of onset affects clinical features or inflammatory severity.

The Naranjo Adverse Drug Reaction Probability Scale [3], with a maximum score of 13, assesses the likelihood of a drug causing an adverse reaction. In these cases, uveitis associated with teclistamab therapy scored 6, indicating a probable association. Points were not awarded for categories such as drug re-administration, placebo response, toxic drug levels (no available test for teclistamab levels in the blood), or dose modifications (standardized regimen).

Teclistamab exerts its therapeutic effect by redirecting T cells to induce lysis of BCMA-expressing myeloma cells, a mechanism that may inadvertently trigger off-target immune activation [1]. Similar to other immunomodulatory therapies associated with uveitis, teclistamab's activation of T-cell pathways could contribute to ocular inflammation [4, 5]. The low incidence of these events, despite the widespread use of teclistamab in clinical trials, suggests that these reactions are rare but clinically significant.

In conclusion, this report adds to the evidence of teclistamab-associated ocular adverse events. Our findings confirm a pattern of anterior sclerouveitis with rapid onset following teclistamab administration, as previously described, while also introducing a distinct phenotype of intermediate uveitis with delayed onset and vitreous involvement. These cases highlight the need for vigilance in monitoring for ocular toxicities in patients receiving teclistamab, as early recognition and treatment can lead to favorable outcomes. Future reports and studies will be critical in elucidating the mechanisms underlying these adverse events and refining management strategies.

Sumit Sharma reports consulting fees from 4DMT, Alimera, Abbvie, Apellis, Astellas, Bausch and Lomb, Clearside, Eyepoint, Harrow, Genetech/Roche, Kodiak, Merck, Regeneron, RegenXBio, Ripple, Volk, and Zeiss with contracted research support from Acelyrin, Gilead, Genetech/Roche, Santen, IONIS, Kodiak. Shahzad Raza has served on an advisory board for Prothena Biosciences and received research funding from Posedia Therapeutics, Janssen, Nexcella Inc. The other authors declare no conflicts of interest.