Systematic review of programmed cell death-1 inhibitor therapy for advanced-stage cutaneous squamous cell carcinoma in solid-organ transplant recipients

Hanania, Hannah L.; Lewis, Daniel

doi:10.1080/09546634.2022.2118516

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Solid-organ transplantation patients under immunosuppression show a 65 to 250 times higher risk of cSCC when compared to healthy individuals [ 4 , 6 ]. The majority of cSCC patients harbor hypermutated tumors due to the mutagenic activity of sun exposure [ 4 , 5 , 22 , 23 ]. The combination of a high number of tumor mutations and the higher incidence in immunocompromised patients makes cSCC a good target for immune therapy [ 8 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

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Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma—A Retrospective Single-Center Study

Kuzmanovszki,

Kiss,

Tóth

et al. 2023

JCM

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Background: The systemic treatment of advanced cutaneous squamous cell carcinoma (cSCC) has seen significant developments in recent years. The anti-PD1 inhibitor cemiplimab has demonstrated efficacy in clinical trials, but real-world data are still limited. Here, we aimed to evaluate the efficacy and the safety of cemiplimab in a real-world clinical setting. Methods: A retrospective analysis was carried out for all patients who received at least two doses of cemiplimab at our department between February 2020 and January 2023. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and adverse events (AEs) were evaluated. Results: Twenty-five patients were included with a median age of 78 (65–82) years. The median treatment duration was 48 (16–72) weeks. Five (20%) patients were immunocompromised. Sixteen patients (64%) developed AEs, including 36% serious AEs (SAEs) of grade ≥ 3. Six patients (24%) were withdrawn from treatment due to the occurrence of AEs. Among the 25 patients, 52% showed an objective response (3 complete and 10 partial responses), 76% had controlled disease and 24% experienced progression. Among the five immunocompromised patients, the ORR was 60%, while the DCR was 80%. Conclusions: This retrospective real-world study revealed that locally advanced or metastatic cSCC could be effectively treated with cemiplimab even in elderly, polymorbid and immunocompromised patients.

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Section: Discussionmentioning

confidence: 99%

“…There are several risk factors for cSCC, such as UV exposure, immunosuppression, elderly age, chronic inflammation, wounds and genodermatoses [ 1 , 2 , 3 ]. Approximately one-fourth of all cases are observed among immunocompromised patients, in particular in solid organ transplant recipients (OTRs) [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma—A Retrospective Single-Center Study

Kuzmanovszki,

Kiss,

Tóth

et al. 2023

JCM

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“…11 Ten to thirty percent of patients experience immune-related adverse events (irAEs) associated with ICIs such as avelumab. 27,28 ICIs can result in irAEs such as autoimmune thyroiditis, and hypophysitis. 22 Hypothyroidism (0.6%) was the irAE that was most frequently reported.…”

Section: Adverse Eventsmentioning

confidence: 99%

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival

Lohray,

Verma,

Wang

et al. 2023

POR

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Introduction:Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings. Areas Covered: Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0-72.7%; complete response rate: 15.8%-37.2%; partial rate: 18.2-42.1%; stable disease: 7.1-30.9%; progressive disease: 7.1-40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed. Conclusion:The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes.

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Acute Allograft Rejection in Kidney Transplant Recipients Treated With Immune Checkpoint Inhibitors: An Educational Case Report

Morrison,

Vinson

2024

Can J Kidney Health Dis

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Rationale: Kidney transplant (KT) recipients have an increased risk of malignancy due to chronic immunosuppression. The emerging use of immune checkpoint inhibitors (ICIs) has been a promising development for the treatment of malignancy, but their use adds to the complexity of immunosuppression management for KT recipients. This case report describes 2 cases of acute rejection in KT recipients following ICI initiation and discusses the balance of malignancy treatment with adequate immunosuppression. Presenting Concerns of Patients: The first patient is a 44-year-old male KT recipient with a diagnosis of metastatic renal cell carcinoma presenting with acute kidney injury 6 days following initiation of an ICI. The second patient is a 73-year-old male KT recipient with a diagnosis of squamous cell carcinoma presenting with acute kidney injury 2 weeks following initiation of an ICI. Diagnoses: Both patients were diagnosed with acute rejection in the setting of reduced immunosuppression and initiation of an ICI. Interventions: Both cases received an increased dose of steroid without improvement of graft function. The first patient subsequently underwent a delayed graft nephrectomy due to complications of acute rejection, whereas the second patient did not undergo nephrectomy. Outcomes: The first patient experienced complications including perioperative bleeding requiring multiple operations, but ultimately stabilized on hemodialysis and showed a durable response to ICI. The second patient remained dialysis-dependent post-ICI treatment and was readmitted with allograft complications leading to his eventual death. Teaching Points: This study underscores the complexity of managing KT recipients diagnosed with malignancy and receiving ICIs. The balance between immunosuppression reduction to treat malignancy and preventing allograft rejection presents a significant challenge. Key considerations include the risk of acute allograft rejection and patient-centered decision-making. These cases highlight the need for further research to develop evidence-based guidelines for managing this patient population. In addition, the patient perspective in this study highlights the importance of careful risk-benefit analysis and the impact of treatment decisions on patient-focused outcomes.

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Systematic review of programmed cell death-1 inhibitor therapy for advanced-stage cutaneous squamous cell carcinoma in solid-organ transplant recipients

Cited by 3 publications

References 45 publications

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma—A Retrospective Single-Center Study

Real-World Experience with Cemiplimab Treatment for Advanced Cutaneous Squamous Cell Carcinoma—A Retrospective Single-Center Study

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival

Acute Allograft Rejection in Kidney Transplant Recipients Treated With Immune Checkpoint Inhibitors: An Educational Case Report

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