Strategies to overcome relapse of immunotherapy-related hepatitis: dose reduction is not the key.

INTRODUCTION: Immunotherapy-related hepatitis accounts for 3-6% of all immune-related adverse events (irAE). Reintroduction of checkpoint inhibitors after irAE is matter of debate, weighing the risk of a relapse of adverse events against the possibility of improving disease control. Pharmacokinetic modelling has changed the paradigm of weight-based dosing to flat dose for checkpoint inhibitors, however, it is currently unknown if this poses underweight (<80 kg) patients to a higher risk of toxicity. Weight-based dosing has been opted as a less dangerous and more economic option, especially for underweight patients. Is dose reduction dosing a strategy to permit checkpoint inhibitors reintroduction after immune-related adverse events?

METHODS: We describe a case of checkpoint inhibitor reintroduction after immunotherapy-related hepatitis, with dose reduction based on weight-based dosing (nivolumab 165 mg Q2w) in a patient with metastatic renal cell cancer.

RESULTS: After three cycles, he had a relapse of hepatitis leading to prolonged steroid use and opportunistic infections.

CONCLUSION: Dose reduction in underweight patients is not the preferred strategy to permit rechallenge after immunotherapy-related hepatitis. Exploration of other secondary prevention strategies is warranted.