Program death-1 inhibitors, a class of immune-checkpoint inhibitors, are now the standard of care in a variety of cancer settings, including cutaneous malignancies, such as melanomas, Merkel cell, and cutaneous squamous cell carcinomas (cSCCs). The clinical trials that led to the approval of the programmed death-1 inhibitor cemiplimab-rwlc (Libtayo®) for use in advanced cSCC excluded patients with autoimmune disease and those that required systemic immunosuppressive treatments, or had undergone solid-organ transplantation. Also, to be eligible, patients had to have adequate organ function. Here, we present the first report of a patient that has been successfully treated with cemiplimab for locally advanced cSCC while simultaneously on dialysis for treatment of renal failure following renal transplant.

© 2023 The Author(s). Published by S. Karger AG, Basel

In 2018, cemiplimab-rwlc (Libtayo®) was the first medication of any kind to be approved by the FDA and Health Canada for the treatment of advanced cutaneous squamous cell carcinoma (cSCC) [1]. In patients with unresectable locally advanced or metastatic cSCC, cemiplimab treatment demonstrated a response rate of 50 and 47%, respectively [2]. Moreover, the 1-year survival of the metastatic cohort was 81% [2]. Classified as an immune-checkpoint blockade therapy, cemiplimab is a human-derived immunoglobulin G4 monoclonal antibody that is a programmed death-1 (PD-1) inhibitor. In the context of an anti-cancer immune response, PD-1 inhibitors prevent the downregulation of the immune system and have demonstrated activity in a wide spectrum of tumor types and agnostically with patients with cancers with mismatch repair deficiency or microsatellite instability [2].

The clinical trials that led to the approval of cemiplimab in advanced cSCC excluded patients with autoimmune disease that required systemic immunosuppressive treatments and those that had undergone solid-organ transplantation. Also, to be eligible, patients had to have adequate organ function. Transplant patients are at increased risk of developing skin cancers, most notably cSCC, given the chronic immunosuppression required to prevent rejection of the transplanted organ. There are several reports of transplanted patients receiving cemiplimab developing a response to treatment but none on dialysis [3, 4]. This approach is not devoid of risk as there are reports of allograft rejection associated with PD-1 blockade in other cancer settings [5, 6]. Here, we present the first report of a patient with a failed renal transplant on dialysis and a locally advanced cSCC of the head and neck that was treated with cemiplimab.

The patient was a 70-year-old male with a history of IgA nephropathy requiring a living donor renal transplant in 2001. He developed allograft rejection in 2018 and required hemodialysis ever since. He was diagnosed with several skin cancers including cSCC involving his head, neck, and arms bilaterally. At the end of 2018, the patient presented with enlarging parotid and neck lymph nodes with no evidence of distant metastatic disease. The patient underwent a parotidectomy and right neck lymph node dissection which identified metastatic cSCC in 2 of 20 lymph nodes. One of the positive lymph nodes was located within the right parotid gland and measured 0.1 cm and the second, located in the submandibular region, measured 7 mm. Figure 1 shows the carcinoma involving subcutis, parotid gland, and an intraparotid lymph node. Subsequently, the patient received adjuvant radiation of 5600 cGy in 28 fractions. Approximately 1 year later, there was an adverse change with a growing right supraclavicular fossa mass measuring 4.4 × 7.1 cm. Due to vasculature involvement, this enlarged node was not amendable to surgical removal. Consequently, palliative radiation (3000 Gy in 10 fractions) was administered and 6 months later the right supraclavicular lesion had responded, now measuring 1.0 × 2.1 cm. A year after the last dose of palliative radiation, there was marked interval enlargement of the heterogeneous nodal mass in the right supraclavicular fossa, now measuring 3.2 × 5.5 cm; the mass was also necrotic and weeping. At this time, his case was reviewed at multidisciplinary rounds, and it was decided to start cemiplimab in August of 2020 (see Fig. 2 for radiographical representation).

Keratinizing moderately differentiated squamous cell carcinoma invading subcutaneous adipose tissue (a, c), parotid gland (b), with a metastasis to an intraparotid lymph node (d). Hematoxylin and eosin-stained sections photographed at ×20 magnification (a, d), ×40 (b), and ×100 (c).

Radiologic imaging of patient case. a Baseline scan from August 2020 prior to treatment. b Disease response during cemiplimab treatment. c Radiographical imaging supporting the duration of response to cemiplimab even after being off treatment for 13 months.

The patient was given cemiplimab at 350 mg intravenously once every 3 weeks. He tolerated treatment well with symptoms of fatigue and rash. While on treatment, the patients creatinine would fluctuate and went as low as 295 μmol/L to as high as 592 μmol/L. It is thought that the fluctuation of creatinine is more attributable to the proximity of blood draw to dialysis session rather than in response to cemiplimab treatment. After 4 cycles of treatment, a restaging scan revealed a response to treatment: the right supraclavicular mass had shrunken to 1.4 × 3.0 cm. Another dose of cemiplimab was administered, but unfortunately the patient developed worsening fatigue and shortness of breath requiring supplemental oxygen. Chest X-ray revealed a left lower lung consolidation. Electrocardiogram showed no ischemic changes, but a troponin peaked at 600 ng/L. Immune-related adverse events were entertained such as myocarditis, but given that his symptoms improved without the administration of high-dose corticosteroids, this was felt to be less likely. The patient recovered from the community-acquired pneumonia, and non-ST elevation myocardial infarction, but based on these complications the decision was made to hold the cemiplimab. In total, the patient received 5 doses of cemiplimab in total.

Routine scans, up to 13 months from the last cemiplimab treatment, revealed stability of disease (see Fig. 2). However, after 16 months from his last dose of cemiplimab, a new nodule deep and inferior to the right sternocleidomastoid muscle was seen on CT scan, measuring 8 × 14 mm (see Fig. 2). A biopsy has confirmed cSCC progression. The original right supraclavicular mass has remained stable with no evidence of metastatic disease in the chest, abdomen, or pelvis. Further treatment with cemiplimab, radiation, or surgery will be discussed at multidisciplinary rounds. A full representation of the timeline for the disease occurrence and treatments is shown in Figure 3. The CARE Checklist has been completed by the authors for this case report, attached as supplementary material at www.karger.com/doi/10.1159/000528414.

Timeline of important events.

This is the first report of a patient that has been successfully treated with cemiplimab for locally advanced cSCC while simultaneously on dialysis for treatment. Although previous reports of cemiplimab use in patients on dialysis are missing from the literature, other PD-1-inhibiting monoclonal antibodies (nivolumab, ipilimumab, and pembrolizumab) have been successfully used as first-line treatments for melanoma, nonsmall cell lung cancer, and metastatic renal cell carcinoma in this setting ([7], reviewed in [8]). The maintained efficacy of these antibodies in patients on dialysis without the requirement of dose adjustment is likely explained by the molecular weight of these products (all between 143 and 148 kDa), which makes them too large to dialyze. Moreover, the pharmacokinetic data support that hepatic nor renal dysfunction should change the pharmacokinetic profiles of PD-1 monoclonal antibodies [1, 7, 9]. Although the kidney is not responsible for metabolism nor excretion of these PD-1 inhibitors, renal dysfunction is an established adverse outcome resulting from the use of these therapies [10–17]. Renal complications are becoming increasingly recognized and may have been previously underestimated. One hypothesis for the development of nephrotoxicity is related to the reprogramming of the immune system leading to the loss of self-tolerance [12]. Another explanation of nephrotoxicity may be due to concomitant drug administration where it has been demonstrated that patients are more likely to have acute kidney injury if they demonstrated a lower baseline estimated glomerular filtration rate, are on a combination of PD-1 inhibitors or taking proton-pump inhibitors [12]. In the case described, the patient was not on any nephrotoxic medications or proton-pump inhibitors, and no worsening renal function developed. Nephrotoxicity from PD-1 inhibitors has been shown to be reversible if the drug is discontinued and the patient is given steroid support.

Patients with transplanted organs and chronic immunosuppressive drugs are at increased risk of malignancy, especially cSCC. Moreover, patients with inadequate organ function, like patients on dialysis, were often excluded from pivotal immunotherapy trials. This case report supports that cemiplimab may be safe and effective to use in patients on dialysis, like other PD-1 inhibitors.

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Dr. J. Monzon sits on advisory boards for BMS, Pfizer, Sanofi, and Taiho and has a grant funding from Merck.

No funding received.

Conceptualization, patient consent, patient data, supervision, review, and editing were provided by Dr. Jose Monzon. Writing the original draft, review, and editing were completed by Stacy de Lima. The pathology review and imaging data, along with the editing of the case report, were provided by Dr. Hyrcza.

All data generated or analyzed during this study are included in this article.

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