The adverse reactions of immunopoint inhibitors are usually related to inflammatory reactions. Drugs with a long half-life are more likely to cause immune-related adverse reactions (irAEs).
Generate new immune responses to autoantigens;
A hyperphysiological response to symbiotic bacteria, such as the gastrointestinal tract or skin
The incidence of all G3/4AES ranged from 7% to 13%. In general, irAEs generally occurred early, mostly within a few weeks to three months after administration, and irAEs did not occur until treatment was terminated, and most immune-related adverse reactions were reversible.
It was also found that drugs with a long half-life were more likely to cause irAEs, so shortening the half-life of PD-1 antibody is an effective strategy to reduce the occurrence of toxic and side reactions of immune point inhibitors.
General principles of irAEs treatment (graded according to CTCAE severity) :
1) Level 1: Not bedridden, not recommended hormone, not recommended other immunosuppressive drugs, continue immunotherapy;
2) Level 2: not bedridden, local or systemic hormone therapy oral 0.5-1mg/kg/d is recommended, other immunosuppressive agents are not recommended, and the use of immunotherapy is suspended;
3) Level 3: hospitalized, systemic hormone therapy orally or intravenously with 1-2mg/kg/d. Patients whose symptoms fail to relieve after 3-5 days of hormone therapy may consider using other immunosuppressive agents under the guidance of a specialist, stop immunotherapy, and seriously discuss whether to recover;
4) Hospitalized treatment, ICU should be considered, systemic hormone therapy, intravenous methylprednisolone 1-2mg/kg/d, and gradually reduce the dosage to 1mg/kg/d after 3 consecutive days. Patients whose symptoms fail to relieve after 3 to 5 days of hormone therapy may consider using other immunosuppressive agents under the guidance of a specialist, and stop immunotherapy permanently.
Note: Patients who have used IMMUNOsuppressants before and have a level 3 or more toxic side effect are less likely to respond to repeated use of immunosuppressants, so use caution
Note: It is very important to pay close attention to the occurrence of toxic and side effects after immunosuppressive therapy. The earlier the toxic and side effects are treated, the greater the chance of recovery.
Such as immune myocarditis, severe immune hepatitis, and so on, treatment is not timely may lead to the patient’s death.
Note: antibiotics may reduce the efficacy of tumor immunotherapy.
Note: Patients may have repeated adverse reactions, so pay attention to monitor their own physical conditions.
Cutaneous toxicity is the most common AEs(34-43%) in patients treated with CTLA-4 and PD-1. Rash, pruritus, and vitiligo are the most common, with reactive cutaneous capillary hyperplasia (but mild and self-limiting) being the most common.
AEs with the greatest impact is pulmonary toxicity, with a low incidence, but note the risk factors (whether there is underlying lung disease, lung infection, history of radiotherapy).
The incidence of stage 5 pneumonia was 0.1%.
The worst prognosis was immune myocarditis with an incidence of 0.06%, but 101 patients with severe myocarditis had 46 deaths.
The median duration of immune myocarditis was 27 days, 76% occurred within 6 weeks, and the shortest was 5 days.