Bullous pemphigoid, an immune-mediated situation chacterized by massive, fluid-filled blisters on the pores and skin, is a uncommon however severe complication of most cancers remedy with immune checkpoint inhibitors (ICIs) which will end in therapy interruption or cessation.
Investigators in Boston report that amongst sufferers receiving ICIs, being aged 70 years or older and having pores and skin most cancers are each important danger elements for bullous pemphigoid. On the plus facet, ICI-induced bullous pemphigoid additionally seems to be a marker for improved tumor responses to remedy.
In a nested case-control research of 5636 sufferers with most cancers who obtained both a programmed loss of life 1 inhibitor similar to pembrolizumab (Keytruda) or nivolumab (Opdivo) or a cytotoxic T-lymphocyte–related protein 4 inhibitor similar to ipilimumab (Yervoy), 35 sufferers (0.6%) developed bullous pemphigoid. The research by Nicole R. LeBoeuf, MD, MPH, from Brigham and Girls’s Hospital in Boston, and colleagues was printed on-line April 20 in JAMA Dermatology.
“What’s attention-grabbing is that 0.6 is a small quantity, however we’re seeing bullous pemphigoid at significantly larger frequency than is predicted within the common inhabitants,” LeBoeuf mentioned in an interview with Medscape Medical Information.
And though bullous pemphigoid has the potential to disrupt ICI remedy, it additionally seems to be a marker for a good tumor response, the investigators discovered.
Their findings recommend that administration of bullous pemphigoid for sufferers receiving ICIs ought to deal with early identification and administration with therapies directed on the particular toxicity, LeBoeuf mentioned.
“If you make a selected analysis like bullous pemphigoid, then you may deal with that particular illness with very focused therapies, similar to omalizumab or dupilumab or rituximab ― issues that aren’t globally immune suppressing like steroid or different T-cell depleting brokers. Research have proven that depleting B cells with anti-CD20 brokers is just not detrimental to immune checkpoint inhibitor remedy,” she mentioned.
Dermatologic AEs Widespread
As beforehand reported by Medscape Medical Information, about 40% of sufferers with most cancers handled with ICIs expertise immune-related dermatologic antagonistic occasions (AEs) that may vary from gentle rashes and hair and nail modifications to unusual however life-threatening problems, similar to Stevens-Johnson syndrome, a type of poisonous epidermal necrolysis, based on members of a European Academy of Dermatology and Venereology activity pressure.
“The fascinating, immune-mediated oncologic response is commonly achieved at the price of immune-related antagonistic occasions (irAEs) which will doubtlessly have an effect on any organ system,” they wrote ready assertion on the administration of ICI-derived dermatologic antagonistic occasions.
LeBoeuf and colleagues word that whereas reported danger elements for idiopathic bullous pemphigoid embody superior age, kind 2 diabetes, use of dipeptidyl peptidase-4 inhibitors, cerebrovascular illness, and neurocognitive illness, danger elements for bullous pemphigoid and different antagonistic dermatologic occasions related to ICIs are much less well-known.
To establish danger elements for bullous pemphigoid in sufferers receiving ICI, the investigators carried out a case-control research nested inside a retrospective cohort research.
They evaluated data for all sufferers within the three Harvard-affiliated hospitals to establish sufferers with ICI-associated bullous pemphigoid from October 2014 by means of December 2020. Management individuals have been all sufferers within the Dana-Farber most cancers registry who obtained ICIs in the course of the research interval.
The investigators selected age at ICI initiation (69 years and youthful or 70 years and older), intercourse, ICI brokers, and most cancers kind as potential danger elements.
They used propensity rating matching primarily based on age, most cancers kind, ICI agent, and variety of ICI cycles to match two management individuals with every case affected person.
Of the 5636 sufferers handled with ICIs in the course of the research interval, 35 (0.6%) developed bullous pemphigoid. The median age was 72.8 years, and 71.4% have been males.
In a multivariate logistic regression mannequin that included 2955 sufferers with full information within the most cancers registry, elements considerably related to creating bullous pemphigoid included age 70 years or older (odds ratio [OR], 2.32, P = .01), having melanoma (OR, 3.21, P < .001), and having nonmelanoma pores and skin most cancers (OR, 8.32, P < .001).
In evaluating the 35 case sufferers with their matched management sufferers, a whole or partial response at first restaging imaging was considerably related to creating bullous pemphigoid (OR, 3.37, P = .01). As well as, there was a better probability of tumor responses to ICIs amongst sufferers with bullous pemphigoid in contrast with matched management sufferers (goal response price, 82.9% vs 61.4%, P = .03).
Prudent Toxicity Administration
Ryan Sullivan, MD, who treats sufferers with pores and skin most cancers at Massachusetts Basic Hospital Most cancers Middle however was not concerned within the research, commented that the findings increase questions in regards to the relationship between pores and skin cancers and immune-related antagonistic occasions.
“It’s compelling that bullous pemphigoid is a pores and skin toxicity and is extra frequent to occur in pores and skin most cancers sufferers,” he famous. “That is a really attention-grabbing discovering, and the rationale that it is attention-grabbing is that it is tougher to know why a presumably antibody-mediated facet impact could be extra prone to have that cross-reactivity the place the tumor began and the place the toxicity occurred,” he mentioned in an interview with Medscape Medical Information.
He famous that the advantages of ICIs for sufferers with pores and skin cancers far outweigh the dangers of dermatologic antagonistic occasions similar to bullous pemphigoid and that ICI-associated occasions require considered administration.
“That is true throughout the spectrum of toxicities: there are clear manifestations of toxicity that we needs to be extra considerate about what’s driving them, extra considerate about what it’s, and extra considerate about treating them, different than simply pouring steroids into sufferers in industrial doses and hoping that every little thing’s going to be OK,” he mentioned.
No funding supply for the research was reported. LeBoeuf reported receiving grants from the Nationwide Institutes of Well being Nationwide Most cancers Institute in the course of the conduct of the research and private charges for serving as a marketing consultant for a number of corporations exterior the research. Co-author Arash Mostaghimi, MD, MPA, MPH, is affiliate editor of JAMA Dermatology however was not concerned in research choice or analysis for publication. Sullivan disclosed consulting for ICI makers Bristol-Myers Squibb and Merck.
JAMA Dermatol. Revealed on-line April 13, 2022. Summary
Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape.
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