Immune-Mediated Hepatotoxicity Associated With Ribociclib: A Multipatient Case Series and Management Strategy

Area of Science:

• Oncology
• Hepatology
• Pharmacology

Background:

• Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are standard for HR+/HER2- metastatic breast cancer.
• Ribociclib, abemaciclib, and palbociclib improve outcomes, but hepatotoxicity is a known side effect, particularly with ribociclib.
• Immune-mediated liver injury from ribociclib is recognized but poorly described, necessitating management strategies.

Purpose of the Study:

• To describe a series of patients with ribociclib-induced liver injury (DILI) exhibiting immune-mediated features.
• To evaluate the efficacy of immunosuppressive therapy in managing this specific DILI presentation.
• To assess the safety and efficacy of alternative CDK4/6 inhibitors in patients experiencing ribociclib-induced hepatotoxicity.

Main Methods:

• Retrospective case series of five patients who developed ribociclib-induced liver injury.
• Assessment of treatment response to corticosteroids and other immunosuppressive agents (tacrolimus).
• Evaluation of subsequent treatment with palbociclib in three patients.

Main Results:

• Hepatotoxicity occurred early in treatment, predominantly within the first few cycles.
• All patients responded to corticosteroids, but three experienced relapse upon tapering.
• Tacrolimus enabled immunosuppression withdrawal in two patients; palbociclib was safely used in three patients without hepatotoxicity recurrence.

Conclusions:

• Ribociclib-induced hepatotoxicity can present with immune-mediated features, requiring prompt monitoring and management.
• Corticosteroids are effective, with additional immunosuppression like tacrolimus potentially needed for sustained response.
• Palbociclib represents a viable alternative for patients who develop hepatotoxicity on ribociclib, allowing continued CDK4/6 inhibition.