Spectrum of Dermatologic Adverse Events Associated With Amivantamab Use

Abstract

This case series describes the different dermatologic adverse events that patients experienced while using amivantamab.

Amivantamab is a bispecific monoclonal antibody that targets epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition factor (MET) and is approved for EGFR exon 20 insertion–mutated advanced non–small cell lung cancer. This alteration portends poor prognosis due to insensitivity to EGFR tyrosine kinase inhibitors.¹

The most common dermatologic adverse events (dAEs) associated with EGFR inhibitors (EGFRIs) are acneiform eruption and pruritus.² Other dAEs include xerosis, fissures, and nail and hair changes.² Although no US Food and Drug Administration–approved monoclonal antibody exclusively targets MET, the tyrosine kinase inhibitors capmatinib and tepotinib are MET inhibitors and have been associated with photosensitivity, acneiform rash, paronychia, xerosis, pruritus, and mucositis.³ The aim of the study was to describe dAEs associated with amivantamab use.

Methods

This case series was conducted at 2 academic health care centers from June 2021 to August 2022. We searched electronic medical records for consecutive cases of dAEs associated with amivantamab that prompted referrals to oncodermatology clinics in the year after Food and Drug Administration approval. Herein, we describe the clinical presentations, response to treatment, and implications for cancer therapy. The Yale University Institutional Review Board approved the study, and patients provided written informed consent. We followed the reporting guideline for case series.

Results

Six patients (mean [range] age, 58 [49-69] years) were treated with amivantamab and developed dAEs (Table).

Table. Patient Characteristics.

Patient No.	Time from treatment initiation to dAE, mo	Cutaneous dAEsa	Treatment of cutaneous dAEs	Nail dAEs	Treatment of nail dAEs	Implications of dAE for amivantamab therapy
1 (Man in his 40s)	3	Acneiform eruption of the scalp (grade 2) complicated by impetiginization (culture results positive for methicillin-susceptible Staphylococcus aureus)	Vancomycin or cefepime, mupirocin ointment, decolonization with zinc pyrithione shampoo and chlorhexidine washes as an inpatient. Cephalexin (500 mg 4 times daily), doxycycline (100 mg twice daily), fluocinolone oil, and aluminum acetate soaks started as an outpatient	Paronychia with pyogenic granulomas	Topical timolol ophthalmic solution or gel under occlusion	Drug stopped, amivantamab reinitiated at 67% of original dose
2 (Woman in her 60s)	1	Acneiform eruption (grade 3) of the scalp and face with hyperkeratotic crust of the scalp	Hydrogen peroxide soaks with debridement in clinic and doxycycline (100 mg twice daily), aluminum acetate soaks, triamcinolone ointment	NA	NA	Drug stopped, amivantamab reinitiated at 67% of original dose
3 (Woman in her 50s)	2	Widespread acneiform eruption (grade 3) with dermatitis of the posterior neck and fissuring of the palms and soles	Doxycycline (100 mg twice daily), clobetasol ointment or triamcinolone cream to body, hydrocortisone ointment to face, antihistamines, and prednisone taperb	Paronychia with pyogenic granulomas	NA	Drug stopped, amivantamab reinitiated at 67% of original dose
4 (Man in his 50s)	3	Widespread acneiform eruption (grade 2) and fissuring of the palms and soles	Doxycycline (100 mg twice daily), triamcinolone cream and cyanoacrylate adhesive for pain due to fissures	Onycholysis, suppurative paronychia	White vinegar soaks, mupirocin ointment	Drug stopped, amivantamab reinitiated at 70% of original dose
5 (Woman in her 50s)	4	Widespread acneiform eruption (grade 3)	Doxycycline (100 mg twice daily), clobetasol ointment, clindamycin solution	Paronychia with pyogenic granulomas	Silver nitrate cautery for pyogenic granulomas in clinic; mupirocin ointment, timolol ophthalmic solution, and white vinegar soaks	Drug stopped, amivantamab reinitiated at 75% of original dose
6 (Man in his 60s)	<1	Acneiform eruption (grade 2) of the scalp, face, upper back, and upper chest	Prednisone (60 mg daily for 7 d), doxycycline (100 mg twice daily), and clobetasol ointment; cephalexin (500 mg 3 times daily), acitretin (10 mg daily), and clobetasol ointment for maintenance	Paronychia with pyogenic granulomas	Silver nitrate cautery for pyogenic granulomas in clinic; clobetasol ointment	Continued amivantamab at original dose

Abbreviations: dAE, dermatologic adverse event; NA, not applicable.

^a Eruptions are graded on a scale of 1 to 5, with 1 representing mild symptoms and 5 representing death associated with the adverse event, based on the Common Terminology Criteria for Adverse Events.

^b The prednisone taper was 30 mg daily for 3 days, 20 mg daily for 3 days, and 10 mg daily for 3 days after each amivantamab infusion.

Patients 1 and 2 developed severe, atypical acneiform eruptions of the scalp. Patient 1 presented with thick branlike crust covering the scalp and eyebrows with purulent exudate and intact pustules; the scalp was boggy to palpation (Figure, A). Biopsy results showed suppurative folliculitis with psoriasiform epidermal hyperplasia (Figure, B). Patient 2 presented with sanguineous crusted plaques of the scalp, forehead, glabella, and perinasal region with thick hyperkeratotic crust of the scalp (Figure, C). Patient 3 presented with neck dermatitis that spread diffusely and flared during infusions. Examination showed eyelid edema, fissured plaque of the posterior neck, inflammatory papules of the cheeks and chest, and scaly pink plaques of the extremities. Patients 4, 5, and 6 presented with widespread acneiform eruptions with severe, classic morphologic features (Figure, D). Treatment regimens included prednisone, acitretin, doxycycline, topical corticosteroids, and antihistamines. Patient 1 received vancomycin, cefepime, and decolonization for impetiginization. Patient 2 required debridement of crusted plaques. Two patients developed fissuring of the palms.

Figure. Dermatologic Adverse Events in Patients Receiving Amivantamab Therapy.

A, A thick branlike crust covering the scalp with copious purulent exudate and scattered intact pustules. B, Histopathological image showing suppurative folliculitis with psoriasiform epidermal hyperplasia (hematoxlin-eosin stain; magnification x10). C, Sanguineous crusted plaques of the forehead, glabellar region, and perinasal region, with thin erythematous plaques on bilateral cheeks and the upper lip. D, Widespread erythematous papulopustular eruption.

Five patients developed nail changes, including dystrophy, onycholysis, paronychia, and pyogenic granulomas. Treatment regimens included vinegar soaks, mupirocin ointment, clobetasol ointment, and topical timolol ophthalmic gel or solution under occlusion. Two patients required silver nitrate cauterization. In 5 patients, amivantamab treatment was stopped and, after dermatologic therapy, was restarted at 67% to 75% of the original dose.

Discussion

This case series highlights the scope of amivantamab-associated dAEs, which may appear atypical in severity, morphologic features, and distribution, potentially due to additive toxic effects associated with dual EGFR and MET inhibition. Two patients developed crusted plaques of the scalp that were more severe than classic acneiform folliculitis. Pathophysiologic features underlying unusual scalp lesions may be associated with MET activity, which can affect follicular growth.^4,5

The role of preventive treatment of dAEs during amivantamab therapy has been unclear given its unique mechanism. A trial showed more than 50% reduction in grade 2 and higher dAEs in patients taking EGFRIs who received preemptive treatment with moisturizers, sunscreen, topical corticosteroids, and an oral tetracycline; this regimen is recommended to be started before EGFRI initiation.⁶ Preventive treatment, including sun protection, should be considered before initiating amivantamab.

The dAEs in this case series showed classic toxic effects associated with EGFRIs and atypical presentations. Despite frequent treatment interruption, dAE management and amivantamab dose reduction allowed for continuation of cancer therapy with a reduction in dAEs for all patients in this series. Study limitations include the small sample from 2 hospital systems. As amivantamab use increases, oncologists and dermatologists need to collaborate to ensure swift diagnosis and management of dAEs.