Cutaneous adverse events are common with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been ...investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.
To assess the nature of dermatitis after exposure to a PD-1/PD-L1 inhibitor and oncologic outcomes associated with dermatitis.
Retrospective, matched, case-control study conducted at a single academic center.
The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). The overall tumor response rate was 65.0% for the case patients and 17.0% for the controls (P = .0007) (odds ratio, 7.3; 95% confidence interval, 2.3-23.1). The progression-free survival and overall survival times were significantly longer for the case patients than for the controls by Kaplan-Meier analysis (P < .0001 and .0203, respectively).
The retrospective design and relatively small sample size precluded matching for all cancer types.
Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The value of PD-1/PD-L1–related dermatitis in predicting cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.
Keratinocytic cancers (KCs), specifically cutaneous squamous cell and basal cell carcinomas, can respond to topical, intralesional, or systemic immunotherapies, but cutaneous adverse events (CAEs) ...may occur. Understanding these risks, early recognition of these CAEs, and effective treatment may enable patients to continue their anticancer immunotherapies without dose impact. Immune checkpoint inhibitor-related CAEs after KCs can have multiple clinical presentations, with specific observed types including psoriasis and bullous pemphigoid. Cutaneous toxicities can require biopsies to confirm the diagnosis, especially in patients who are not responsive to topical or oral steroids, since the selection of biologic drugs depends on accurate diagnosis. Different types of CAEs from immune checkpoint inhibitors have been associated with different oncologic outcomes in various primary cancer types, and this remains to be determined for KC patients. CAE characterization and management after immune checkpoint inhibitors in KC patients is a rapidly growing field that needs specific and prospective studies.
Clinical trials report occurrence of nonmelanoma skin cancers (NMSCs) with ruxolitinib in patients with polycythemia vera (PV) or myelofibrosis (MF); however, the level of risk and effect of ...covariates are not known in the real-world setting.
To systematically assess the risk of developing NMSC after ruxolitinib exposure in patients with PV or MF.
A 10-year retrospective cohort of patients with PV or MF at Stanford Medical Center was identified and matched according to age, gender, race, Charlson Comorbidity Index, disease diagnosis, and follow-up time. The main outcome measure was hazard ratio (HR) for NMSC (comprised of basal cell carcinoma and squamous cell carcinoma SCC) after ruxolitinib exposure, adjusted for covariates.
The study cohort consisted of 564 patients (188 exposed to ruxolitinib for at least 4 weeks, 376 unexposed). Ruxolitinib-exposed patients with PV or MF had an adjusted NMSC HR of 2.69 (95% CI, 1.03-7.02). In particular, ruxolitinib exposure was associated with SCC (HR, 3.24; 95% CI, 1.45-7.22), with non–Janus kinase 2-mutated patients showing even higher SCC risk (HR, 7.40; 95% CI, 2.54-21.63).
Retrospective design.
Our real-world results indicate that SCC risk is increased in patients with PV or MF taking ruxolitinib and support consideration of skin cancer monitoring.
Mogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) is difficult to differentiate from ...cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin.
To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges.
This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease.
At least 1 dose of mogamulizumab.
Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach.
The study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 52.6% male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate.
This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these ...skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. We systematically review according to drug-targeting pathway the cutaneous AE profiles of these drugs, and offer insight when possible into whether pharmacologic target versus immunologic modulation primarily underlie presentation. We include discussion of tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib), blinatumomab, ibrutinib, idelalisib, anti-B cell antibodies (rituximab, ibritumomab, obinutuzumab, ofatumumab, tositumomab), immune checkpoint inhibitors (nivolumab, pembrolizumab), alemtuzumab, brentuximab, and proteasome inhibitors (bortezomib, carfilzomib, ixazomib). We highlight skin reactions seen with antiliquid but not solid tumor agents, draw attention to serious cutaneous AEs that might require therapy modification or cessation, and offer management strategies to permit treatment tolerability. We emphasize the importance of early diagnosis and treatment to minimize disruptions to care, optimize prognosis and quality of life, and promptly address life-threatening skin or infectious events. This evolving partnership between oncologists and dermatologists in the iterative characterization and management of skin toxicities will contribute to a better understanding of these drugs' cutaneous targets and improved patient care.
To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.
To report the cases of 3 consecutive patients with pembrolizumab-induced ...eruptive KAs and their management.
Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.
All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.
Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.
Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.
The US health care system generates substantial global waste. Skin biopsies are frequently performed by dermatologists and represent a practical and scalable opportunity for waste reduction ...interventions in dermatology clinics.
To develop and implement a systematic framework for decreasing skin biopsy tray waste in dermatology clinics.
This quality improvement study was conducted at 4 outpatient clinic sites within a single institution between October 2021 and April 2022. The clinic site with the greatest skin biopsy tray waste production was selected for intervention. Waste audits before and after the intervention quantified the number of wasted supplies per skin biopsy tray in dermatology clinics. The participants were dermatology residents, faculty, nurses, medical assistants, and clinic managers.
Provision of educational materials about climate change and health care and standardizing biopsy tray setup to decrease wasted supplies.
Quantity of wasted skin biopsy tray supplies (gauze squares, alcohol pads, cotton swabs, and adhesive bandages) before and after interventions.
In waste audits in 4 outpatient dermatology clinics (comprising 98 skin biopsy trays), prior to intervention, 100% of skin biopsy trays had more than 2 wasted supplies within targeted outpatient dermatology clinics at the Stanford Cancer Institute with a mean (SD) of 10.1 (3.4) wasted items per biopsy tray. Following the quality improvement-based interventions, only 16% of skin biopsy trays had more than 2 wasted supplies and the mean (SD) number of wasted supplies per tray decreased to 1.6 (1.3).
Results of this quality improvement study suggest that through collaboration with all members of the clinical team including physicians, medical assistants, nurses, and clinic managers, skin biopsy tray setup modifications may be associated with reduced waste in outpatient dermatology clinics. This study presents a framework that accounts for different factors in the production of waste in individual clinic settings, and thus can be adapted within additional dermatology clinics.
Background
Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint ...T‐cell receptor programmed death 1 (PD‐1) and the PD‐1 ligand, programmed death ligand 1 (PD‐L1). Various immune‐related toxicities have been associated with these drugs including, most commonly, skin rashes.
Methods
Five cases of lichenoid dermatitis, including one case of lichenoid mucositis and one case of lichen sclerosus, associated with anti‐PD‐L1 and anti‐PD1 therapy were compared with three biopsies of non‐drug‐related lichen planus (LP) and three lichen planus‐like keratoses (LPLK) used as controls.
Results
Histopathologic and immunophenotypic analysis of these lichenoid lesions demonstrated significantly greater histiocytic infiltrates than observed in control lichenoid reactions (p = 0.0134). We also observed increased spongiosis and epidermal necrosis. No significant differences were seen in expression of CD3, CD4:CD8, CD20, PD‐1, CD25, Foxp3, CXCL13 and PD‐L1 expression.
Conclusions
These findings expand the literature of immune‐related toxicities of PD‐L1 and PD‐1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.
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