ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period < 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3–4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.
Purpose: Timeliness of systemic therapy initiation for advanced lung cancer is highly dependent on pathology and molecular pathology laboratory services. Here, we aimed to prospectively evaluate liquid biopsy as a potential strategy to expedite systemic therapy decision-making in lung cancer management. Patients and Methods: This prospective cohort study included consecutive patients with suspected lung cancer seen at the time of initial specialist consultation who underwent both liquid and solid tumour biopsy (group A) and patients with confirmed lung malignancy who underwent solid tumour biopsy alone (group B), between 1 February 2022 and 31 May 2023. Due to laboratory factors, liquid biopsies were processed in batches of 13, whereas solid tumour biopsies were processed individually upon receipt, as per standard practices. Co-primary endpoints included the time from solid versus liquid biopsies to biomarker reporting and palliative systemic therapy initiation. Results: A total of 324 patients were included in the study. The median time from date of blood draw to date of liquid biopsy result was 78 days. For group A (n = 50), the median time from date of solid tumour biopsy to biomarker reporting was 22 days, and the median time from date of solid tumour biopsy to palliative systemic therapy was 42 days. The median time from date of liquid biopsy blood draw to palliative systemic therapy initiation was 56 days. For group B (n = 274), the median times from date of biopsy to biomarker reporting and to palliative systemic therapy initiation in all patients were 22 and 47 days, respectively. Conclusions: While we did not demonstrate improvement in timeliness of biomarker reporting or systemic therapy initiation with liquid biopsy, several barriers leading to delay in liquid biopsy reporting were identified due to unexpected COVID-19-related supply chain disruption and the cost-limiting need to batch sample analysis. Further studies that address the identified barriers are warranted to assess the potential improvement in timeliness of care, should liquid biopsy analysis be implemented in real-time.