Adverse reactions to immunotherapy may indicate a good effect?

Adverse reactions to immunotherapy may indicate a good effect?   The latest research shows that adverse reactions have occurred, which may indicate better efficacy of immunotherapy.

In recent years, immune checkpoint inhibitors have achieved remarkable clinical effects in various malignant tumors such as lung cancer, melanoma, kidney cancer, head and neck tumors, colorectal cancer, etc., and have become subsequent to surgery, chemotherapy, radiotherapy and targeting. Important means after treatment.

At the same time, these drugs inevitably bring immune-related adverse events (immue-related adverse events, irAEs), such as skin, gastrointestinal tract, liver, endocrine and other rare inflammatory reactions, of which skin toxicity is the most common.

Some patients may suffer from irAEs during immunotherapy. However, the latest research shows that there are adverse reactions, which may indicate that the efficacy of immunotherapy is better.

In order to clarify the relationship between the adverse reactions and curative effects of immunotherapy, this article sorts out the latest research results.

Study One

Not long ago, a cohort study published in “JTO” prospectively evaluated the relationship between early adverse reactions related to immunotherapy and the efficacy of Nivolumab. This study included 43 patients with stage IIIB or IV non-small cell lung cancer (NSCLC) who had previously received first-line or more chemotherapy.

The results showed that patients with rash or itching within 2 weeks and 6 weeks had longer disease-free survival after Nivolumab treatment; patients with rash or itching within 2 weeks and 6 weeks after treatment had better remission rates Related.

Study Two

Another study published in “Lung Cancer” included 38 patients with lung cancer, all of whom were treated with Nivolumab. At the end of data collection, 14 irAEs were observed in 11 patients. Surprisingly, patients with irAEs had significantly better results with Nivolumab.

The results show that:

• The objective response rate for patients with irAEs was 63.6%, while the objective response rate for patients with non-irAEs was 7.4%.
• The average progression-free survival time of patients with irAEs has not yet reached (more than 91 days), while the average progression-free survival time of patients with non-irAEs is 49 days.

Study Three

A study published in “JAMA Oncology” in 2017 found that after using PD-1 immune checkpoint inhibitors, the progression-free survival (PFS) and overall survival (OS) of patients with irAEs were significantly better than those without Patients with adverse reactions.

The study retrospectively analyzed 134 patients with advanced NSCLC from multiple medical centers. All of them received Nivolumab treatment. Adverse reactions were observed and recorded every 6 weeks after the start of treatment. The correlation between lifetimes.

The study found that the overall effective rate of patients with adverse reactions was significantly higher than that of those without, being 52.3% and 27.9%, respectively.

Further analysis found that the median progression-free survival of patients in the adverse reaction group was 9.2 months, which was significantly higher than that in the non-adverse reaction group (4.8 months);

In terms of overall survival, the adverse reaction group did not reach the median overall survival (more than 12 months), while the median overall survival of the non-adverse reaction group was 11.1 months.

Further subgroup analysis of adverse reactions found that skin toxicity and endocrine toxicity are closely related to longer disease progression-free survival;

At the same time, skin toxicity is also closely related to longer overall survival, while endocrine toxicity is not related.

Study Four

A recent study published in “JAMA Oncology” also confirmed that irAEs may be related to efficacy. Researchers analyzed data from 623 patients with advanced lung cancer from 5 medical centers.

The results showed that among the 623 patients, 148 patients had at least one treatment-related adverse event, accounting for 24%. The four most common adverse reactions are pneumonia, thyroiditis, hepatitis and dermatitis. Fifty-eight patients had adverse reactions of more than two organs. This situation was a multi-system adverse reaction, the proportion was 9.3%.

Efficacy analysis shows:

The median survival time of patients without irAEs is 8.7 months, the median overall survival time of patients with one irAEs is 12.3 months, and the median overall survival time of patients with two or more irAEs is as high as 21.8 Months.

The median progression-free survival of patients without irAEs is only 2.8 months. The median progression-free survival of patients with one irAEs is 5.1 months, and for patients with two or more irAEs, the median progression-free survival is 10.9 months.

It is not clear what causes the occurrence of irAEs, but a large number of T cell infiltrations have been found in diseased tissues.

According to existing clinical studies, possible mechanisms include the overactivation of effector T cells, decreased regulatory T cell function, and toxic effects of macrophages and neutrophils after inhibiting CTLA-4, PD-1 or PD-L1 Various factors, such as the massive release of interferon gamma and tumor necrosis factor, and antibodies produced by B cells, lead to autoimmune dysfunction and a series of clinical adverse reactions.

Fortunately, most adverse reactions of immunotherapy respond well to steroids and can be controlled in time.

The adverse reactions related to immunotherapy may have a certain correlation with the curative effect, but they are not positively correlated, and are only related to some adverse reactions. Existing studies have shown that immune-related adverse reactions, especially skin toxicity or endocrine system toxicity, may show better curative effects.

Of course, the relationship between immune-related adverse reactions and curative effects still needs more clinical trials to prove. On the one hand, clinicians should actively help patients deal with irAEs and explain that the occurrence of irAEs may indicate a better curative effect. On the other hand, they should also pay attention to collecting data and conducting related clinical trials to provide more evidence-based evidence for immunotherapy.

(source:internet, reference only)

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