June 13, 2024

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cirAEs may be the simplest immunotherapy prognostic indicator!

cirAEs may be the simplest immunotherapy prognostic indicator!


cirAEs may be the simplest immunotherapy prognostic indicator!

JAMA Sub-Journal: It may be the simplest immunotherapy prognostic indicator!


We all know that immunotherapy has changed the face of cancer treatment in the past 10 years, but more than one-third of patients with immune-related adverse effects (irAEs) develop immune-related adverse effects (irAEs), and cutaneous immune-related adverse It is also fairly common in treated patients, with an incidence of 20 to 40 percent [1].


Recently, a team of dermatologists at the Massachusetts General Hospital of Harvard Medical School published a short report in JAMA Dermatology [2].

They found that patients who developed cirAEs after PD-1/PD-L1 inhibitor treatment had more cirAEs than those who did not.

There was a good survival benefit, with a 22.2% reduction in the overall risk of death in patients with cirAEs compared with patients who did not (HR=0.778, P < .001). This study provides a powerful predictor of immunotherapy response and immunotherapy prognosis.


cirAEs may be the simplest immunotherapy prognostic indicator!


Research on irAEs as a prognostic indicator has been hot recently. irAEs include more than 70 pathological manifestations, involving almost all organs [3], and they are graded in severity.

It is difficult to study in general, and patients with severe irAEs often require drug discontinuation. , and even to permanently discontinue immunotherapy [4], such irAEs often have no opportunity and significance as a prognostic indicator.

The overall degree of cirAEs is relatively mild, which basically does not affect the treatment plan of patients, and has the potential to be used as a prognostic indicator.


The study was a population-level retrospective cohort study using data from the TriNetX Diamond Network large clinical database, including health records and administrative data from more than 200 million patients in Europe and the United States.

The database was searched for 7,008 patients with tumors of the digestive system, bronchi and lungs, skin, and urinary tract that appeared after treatment with PD-1 and PD-L1 inhibitors. cirAEs.

The researchers matched them with 7008 patients who did not develop cirAEs after treatment with PD-1 and PD-L1 inhibitors as controls.


cirAEs may be the simplest immunotherapy prognostic indicator!



cirAEs were defined as any new skin-related diagnosis including skin eruptions within 6 months of first receiving ICI.

Among them, there are as many as 17 cirAEs with definite diagnosis, including dermatomyositis, maculopapular rash, erythroderma, drug eruption and non-specific drug reaction, pruritus, xerosis, rash and other non-specific skin rash, etc.


The data analyzed showed that the median survival time of patients who developed cirAE was 1278 days, while the median time of control group of patients who did not develop cirAE was 1024 days.


Analysis of each of these skin disease categories using Cox proportional hazards models found that the vast majority of cirAEs were significantly associated with immunotherapy response and patient survival.

The HR for any cirAE was 0.778 (95% CI, 0.726-0.834; P < 0.001), and statistically significant cirAEs included pruritus (HR, 0.695; 95% CI, 0.602-0.803; P < 0.001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897; P = 0.001), Sjogren’s disease (HR, 0.626; 95% CI, 0.469-0.834; P = 0.001), nonspecific rash (HR, 0.704; 95% CI, 0.634-0.781; P < 0.001), but hyperhidrosis (HR, 1.381; 95% CI, 0.961-1.985; P = 0.08) and mucositis (HR, 1.161; 95% CI, 0.920-1.466; P = 0.21) ) did not show a better survival benefit.


cirAEs may be the simplest immunotherapy prognostic indicator!

Risk profile of different cirAEs

Sensitivity analysis explored the effect of time boundary on the conclusions, and analyzed the overall HR of 3 months, 9 months, and 1 year as the time boundary, and all came to the same conclusion.


The study provides a strong prognostic indicator for patients receiving immunotherapy, but the study also has certain limitations.

For example, the sample size for the diagnosis of some rare cirAEs was too small to draw corresponding statistically significant conclusions.

The study used the International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10), to identify cirAEs, leading researchers to be unsure whether skin rashes were cirAEs or common rashes.


In addition to this, the TriNetX database has data records from various institutions in Europe and the United States, often resulting in data inconsistencies, and population-level databases have inherent internal heterogeneity.

However, methods using administrative data have produced generally consistent predictions of cirAE occurrence and prevalence compared to manually registered data.

This study suggests that the occurrence of cirAE is a good clinical predictor, but we still need to further study the immune mechanism and provide new ideas for the understanding of immune response.

What remains to be explored is the relationship between cirAE management and overall survival, and whether interruption or discontinuation of ICI therapy in the presence of higher levels of toxicity is clinically worthwhile or associated with overall survival.








1. Phillips GS, Wu J, Hellmann MD, et al. Treatment Outcomes of Immune-Related Cutaneous Adverse Events. J Clin Oncol. 2019;37(30):2746-2758. doi:10.1200/JCO.18.02141

2. Tang K, Seo J, Tiu BC, et al. Association of Cutaneous Immune-Related Adverse Events With Increased Survival in Patients Treated With Anti–Programmed Cell Death 1 and Anti–Programmed Cell Death Ligand 1 Therapy[J]. JAMA dermatology , 2022.

3. Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021;184(21):5309-5337. doi:10.1016/j.cell.2021.09. 020

cirAEs may be the simplest immunotherapy prognostic indicator!

(source:internet, reference only)

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