Management of immune-related cutaneous adverse events with dupilumab

Abstract

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70–90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.

Immunotherapy‐induced eczema treated with dupilumab

“…6 Pathophysiology could be related to shared epitopes between malignant cells and skin cells, resulting in a T-cell response with self-reactivity and autoimmunity. 3 We also found a correlation between severe cirAEs and elevated level of total serum IgE and eosinophils, 4 which are markers of T-helper 2 cell response.…”

“…4 Dupilumab, an interleukin-4 (IL-4) alpha and IL-13 alpha receptors antagonist, is being explored as a novel therapeutic option for the treatment of eczema, with a less immunosuppressive effect than corticosteroids. 3 As demonstrated by these cases, dupilumab may be a new, useful and safe steroidsparing drug in oncologic patients suffering from ICIinduced eczema, but other studies will be necessary to confirm this theory.…”

“…2 They occur in 70%-90% of patients undergoing this kind of treatment. 3 Recently, we found psoriasiform, morbilliform and lichenoid dermatoses associated with ICI, bullous disorders (like bullous pemphigoid) and severe cutaneous adverse events. 1,2,4 We report two cases of histology-confirmed eczema developed under the treatment with ICI, successfully managed with dupilumab.…”

“…Cristian Fidanzi 2 Nicolò Mori 2 Gianna Musettini 3 Samanta Cupini 4 Cecilia Barbara 4 Giacomo Allegrini 4 Giovanni Bagnoni 1 Agata Janowska…”

Editorial: Stevens Johnson syndrome: past, present, and future directions

“…Chen et al and Kurian et al highlight SJS/TEN occurring in association with novel agents: the epidermal growth factor receptor tyrosine kinase inhibitor toripalimab and the α-specific PI3K inhibitor alpelisib. Kuo et al ( 5 ) highlight the addition of severe cutaneous immune related adverse events associated with immune checkpoint inhibitors and highlight knowledge and evidence gaps related to diagnosis and treatment. The presentation can vary from SJS mimickers such as lichenoid and autoimmune bullous disorders to presentations more in keeping with traditional SJS/TEN.…”