4.5.2 General Considerations on Monitoring
The management of a side effect is independent of the checkpoint inhibitor that caused it.These drugs all cause the same spectrum of side effects, but with differing frequencies.Anti-PD-L1 antibodies do not interrupt the interaction between PD-1 and PD-Ligand 2, but have similar side effects.Avelumab is the only checkpoint inhibitor that commonly causes infusion reactions (e.g.,back pain, hypotension).Thus, according to the manufacturer’s instructions, it should be given after premedication with acetaminophen and an antihistamine, at least for the first four infusions [44,45].
The goals of side-effect management are:
(1) To detect and diagnose side effects, including rare ones;
(2) To prevent severe and lethal side effects;
(3) To treat side effects appropriately and without delay;(https://www.daowen.com)
(4) To interrupt, terminate, or continue anti-tumor therapy as appropriate;
(5) To help patients deal optimally with the consequences of side effects.
Before starting treatment, patients should be explicitly informed that the efficacy of checkpoint inhibitors is not diminished even if they must be discontinued because of side effects.If they are not so informed, they might be disinclined to report side effects for fear of having to stop the treatment.The patient’s family should also be present during informed consent discussions, as the endocrine or neurological side effects may result in a loss of drive or in personality changes that can hinder the patient’s ability to seek help independently [46].
Patients should be monitored before treatment and at regular intervals during treatment, i.e., before every cycle of monotherapy and once a week in patients receiving ipilimumab and nivolumab,clinical symptoms and laboratory abnormalities (electrolyte changes, transaminases, lipase/amylase,creatine kinase, thyroid function tests, creatinine, complete blood count and differential).If a side effect is suspected, the origin of the symptoms should be investigated before the next administration of a checkpoint inhibitor [46, 47].
Side effects can also arise long after the termination of checkpoint-inhibitor therapy, as is shown by a reported case of paraplegia arising five months after the end of treatment with ipilimumab.The German Federal Institute for Drugs and Medical Devices recommends the continuation of monitoring for at least five months after the last dose; we continue to monitor patients for up to two years after the last dose [46, 48].