Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms for a broad spectrum of malignancies. Because immune checkpoint inhibitors rely on immune reactivation to eliminate cancer cells, they can also lead to the loss of immune tolerance and result in a wide range of phenomena called immune‐related adverse events (irAEs). At our institution, the management of irAEs is based on multidisciplinary input obtained at an irAE tumor board that facilitates expedited opinions from various specialties and allows for a more uniform approach to these patients. In this article, we describe a case of a patient with metastatic urothelial carcinoma who developed a maculopapular rash while being treated with a programmed death‐ligand 1 inhibitor. We then describe the approach to management of dermatologic toxicities with ICIs based on the discussion at our irAE Tumor Board. Key Points Innocuous symptoms such as pruritis or a maculopapular rash may herald potentially fatal severe cutaneous adverse reactions (SCARs); therefore, close attention must be paid to the symptoms, history, and physical examination of all patients. Consultation with dermatology should be sought for patients with grade 3 or 4 toxicity or SCARs and prior to resumption of immune checkpoint inhibitors for patients with grade 3 or higher toxicity. A multidisciplinary immune‐related adverse events (irAE) tumor board can facilitate timely input and expertise from various specialties, thereby ensuring a streamlined approach to management of irAEs.

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System

“…Overall, our data (a) confirmed the variegate pattern of cutaneous toxicity , including nonspecific manifestations such as rash maculopapular and pruritus, as well as serious irAEs and SCARs, thus making a timely consultation with dermatologist pivotal to minimize unnecessary drug interruption ; (b) found a differential reporting between anti‐PD1/PDL1 drugs (psoriasis, dermatitis psoriasiform, pemphigoid, and cutaneous sarcoidosis) and anti‐CTLA4 medications (acute febrile neutrophilic dermatosis and erythema nodosum) ; and (c) recorded a high proportion of death in young adults with SCARs, especially TEN (83% in adults aged 40–49), with a delayed latency as compared with recently published data on anticancer drugs (mean 46 vs. 18 days ), in keeping with immune‐related basis. This conflicts with the algorithm of drug causality for epidermal necrolysis (ALDEN), which was validated on heterogeneous drugs and suggested that late events are unlikely to be drug related ): we invite clinicians to submit complete high‐quality reports, as recommended by the Side Effect Reporting in Immuno‐Oncology (SERIO) working group .…”

“…Immune checkpoint inhibitors (ICIs), by blocking cytotoxic T‐lymphocyte antigen 4 (CTLA4) and programmed cell death 1 (PD1) or its ligand (PDL1), can cause a unique set of immune‐related adverse events (irAEs) . Although these toxicities are usually manageable, fulminant and fatal events do occur , and this calls for closer collaboration among oncologists and other specialties to ensure personalized management .…”

Immune-Related Adverse Events in the Setting of PD-1/L1 Inhibitor Combination Therapy

“…Patients who do not respond to corticosteroids or who have recurring immune‐related colitis following a corticosteroid taper may require treatment with the antitumor necrosis factor‐α antibody infliximab. As noted above, published guidelines describing irAEs are focused on toxicity secondary to CTLA‐4 and PD‐1/L1 monotherapies or to the concurrent administration of both types of ICIs. Since co‐administration of another type of therapy (e.g., chemotherapy with a PD‐1/L1 inhibitor) may confound the diagnosis of immune‐related colitis and lead to the delay of a suitable remedy, current immunotherapy management guidelines should be applied judiciously.…”

“…Although further study is needed, recent reports highlight the potential detrimental effect on anticancer response of high‐dose steroids at the onset or during PD‐1/L1 inhibitor treatment and thus the need to continue to refine treatment algorithms for irAEs based on available evidence. Similar to the approach used for PD‐1/L1 inhibitor monotherapy , the diagnosis and management of irAEs in patients receiving combination therapy will require an integrated team of oncologists and specialists.…”

“…Whereas mild irAEs can generally be treated supportively, severe toxicity requires urgent intervention and, in some cases, may be fatal . The recognition that irAEs may arise in patients receiving PD‐1/L1 inhibitors has prompted the coordination of multidisciplinary groups to scrutinize these toxicities and the development of consensus guidelines by professional organizations to diagnose and manage them .…”