Severe Pustular Drug Eruptions From Amivantamab: A Case Series

Amivantamab is a bispecific antibody that targets epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) receptors to treat advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations [1]. Understanding adverse events from amivantamab is essential because early recognition and proactive management of toxicities help preserve therapy and quality of life. Scalp toxicities were not captured in the amivantamab Phase 3 clinical trial; however, erosive pustular dermatosis (EPD)-like eruptions have been described recently [2-4]. We describe three patients whose adverse events illustrate severe pustular drug eruptions, including EPD with scarring. This retrospective case series was conducted from April 2024 to August 2025. Three patients were identified following an intradepartmental discussion of severe amivantamab-induced eruptions. The Cleveland Clinic Institutional Review Board declared this study exempt, and patients provided written informed consent for publication of medical information and photographs. Three women aged 63, 75, and 77 years were treated with amivantamab, carboplatin, and pemetrexed for stage IV NSCLC (Table 1). Patient 1 developed scalp erosions and an acneiform rash after 4 months of therapy (Figure 1A). Amivantamab was administered for 6 months, and she showed improvement on prednisone, doxycycline, and topicals (Mendeley Data: https://data.mendeley.com/datasets/ssp6c89ymg/3). However, rechallenge elicited severe EPD after 1 week (Figure 1B). Amivantamab was permanently discontinued. There was difficulty accessing isotretinoin, so acitretin was started. Patient 1's EPD resolved after 3 months, but scarring alopecia remained (Mendeley Data: https://data.mendeley.com/datasets/ssp6c89ymg/3). Patient 2 presented with scalp erosions after 1 month of therapy. She received doxycycline and topicals while continuing amivantamab; unfortunately, her erosions progressed to EPD at 2 months (Figure 1C). Amivantamab was permanently discontinued, and her eruption improved. Patient 3 presented with crusted erosions of the face and bilateral finger web spaces. Amivantamab was administered for 2 months, and she showed improvement with systemic corticosteroids, doxycycline, and topical treatments. However, her eruption worsened 1 week after rechallenging (Figure 1D). Amivantamab was permanently discontinued. She experienced substantial improvement after 2 months of isotretinoin. This case series of Common Terminology Criteria for Adverse Events Grade 3 amivantamab cutaneous toxicities illustrates a spectrum of severe eruptions requiring permanent discontinuation. Cutaneous adverse events are common with amivantamab [1-3], with 31% of patients in the phase 3 PAPILLON trial experiencing an acneiform rash [1]. However, such eruptions typically do not lead to treatment discontinuation (only 5% of patients in the PAPILLON trial and 5%–11% in subsequent studies) [1, 3]. Eruptions can less commonly involve the scalp, typically as scalp folliculitis, and less often as EPD [2-4]. The current case series describes the first reported case of amivantamab-induced scarring alopecia to our knowledge, as the patients in previous cases experienced hair regrowth [4]. Importantly, two patients improved while amivantamab was temporarily held, but worsened substantially after rechallenging. Clinicians should be aware of the possibility of increased severity and scarring of subsequent eruptions. Although intravenous antibiotics were deferred in these cases, given the marked improvement with corticosteroids, clinicians should also be aware that bacterial infections can clinically mimic pustular drug eruptions. As amivantamab is typically reserved for patients with NSCLC whose disease has progressed on conventional chemotherapy [1], minimizing treatment interruptions due to adverse events is a priority. Management consists of topical corticosteroids, topical clindamycin, oral doxycycline, systemic retinoids, and/or systemic corticosteroids [3]. Also, doxycycline and emollients 14 days before amivantamab initiation can reduce the risk and severity of cutaneous toxicities [5]. Prompt recognition and aggressive treatment of severe cutaneous adverse events allow drug continuation in some patients, and early dermatology consultation and psychological support are important. The eruptions in this case series more accurately describe the spectrum of adverse events associated with this life-saving drug and highlight challenges with current management approaches. The authors have nothing to report. All patients in this manuscript have given written informed consent for disclosure of the following specific information related to their conditions and treatment, as well as the identifying photos contained herein. The authors declare no conflicts of interest. The authors have nothing to report.