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Survivorship and Immune Checkpoint Inhibitors

Findings from a series of long-term survivors with melanoma, renal cell carcinoma and non–small cell lung cancer
21 Jul 2020
Cancer Immunology and Immunotherapy

A group of US investigators led by James Randall Patrinely Jr. of the Vanderbilt University School of Medicine in Nashville, TN reported in the August 2020 issue of the European Journal of Cancer  findings from a series of patients with melanoma, renal cell carcinoma (RCC) and non–small cell lung cancer (NSCLC) who survived longer than two years after treatment with PD-1 and PD-L1 inhibitors. They reported encouraging findings with durable responses and favourable health-related quality of life (HRQoL) outcomes. Chronic side events may be more common than previously thought although no clear chronic adverse cardiometabolic effects were observed.

The study team wrote in the background that PD-1 and PD-L1 inhibitors produce durable responses in many cancers. However, the long-term effects of these immune checkpoint inhibitors are not well defined. It prompted them to identify the toxicities, health outcomes and HRQoL among long-term survivors treated with PD-1 and/or PD-L1 inhibitors.

The authors assessed patient and tumour characteristics, immune-related adverse events, cardiometabolic parameters (glucose, blood pressure, body mass index [BMI]), body composition (using automated body composition analyser, computed tomography and Slice-o-matic software) and HRQoL outcomes from 217 patients with melanoma, RCC and NSCLC between 2009 and 2017 with survival longer than two years after treatment with PD-1 and/or PD-L1 inhibitors. The patients received treatment between 2009 and 2017.

Among included patients, most were men (70.3%). An average age at initiation of therapy with PD-1 and/or PD-L1 inhibitors was 61.0 years. Median BMI was 28.5.

Median overall survival was not reached; 33 patients (15.2%) died during the follow-up, primarily from progressive cancer (n = 28).

At the last follow-up, most patients had performance status 0 (38%) or 1 (41%) according Eastern Cooperative Oncology Group.

There was no difference in blood pressure, glucose or BMI from baseline to two years after treatment initiation. Body composition showed increased adiposity (p = 0.05), skeletal muscle mass (p = 0.03) and skeletal muscle gauge (p = 0.04).

The study team observed chronic immune-related adverse events at the last follow-up including hypothyroidism (10.6%), arthritis (3.2%), adrenal insufficiency (3.2%) and neuropathy (2.8%).

New diagnoses of type 2 diabetes (6.5%) and hypertension (6.0%) were observed, with uncertain relationship to PD-1 and/or PD-L1 inhibitors.

Patient-reported outcomes compared favourably with cancer and general populations, although younger age (p = 0.003) and need for subsequent therapy (p = 0.03) were associated with worse HRQoL outcomes. 

The authors concluded that most patients who survive longer than 24 months after treatment with PD-1 and/or PD-L1 inhibitors had durable benefit. HRQoL outcomes compared favourably to unselected cancer cohorts. Chronic immune-related adverse events may be more common than previously thought. No obvious long-term adverse cardiometabolic signals were noted. 

Reference

Patrinely JR Jr., Young AC, Quach H, et al. Survivorship in immune therapy: Assessing toxicities, body composition and health-related quality of life among long-term survivors treated with antibodies to programmed death-1 receptor and its ligand. European Journal of Cancer 2020; 135:211-220. DOI: https://doi.org/10.1016/j.ejca.2020.05.005.

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