Venetoclax in combination with azacitidine induced remission in a cat with relapsed myelodysplastic syndrome following failure of azacitidine monotherapy

Summary Myelodysplastic syndromes (MDS) are rare in cats, and relapse after azacitidine is difficult to manage. A 3‐year‐old, neutered, male British shorthair cat with MDS with refractory anaemia with excess blasts achieved three remissions on azacitidine (35 mg/m 2 subcutaneously for 3–4 days every 21 days), but relapsed with severe cytopenias and splenomegaly. Azacitidine re‐challenge failed, requiring four whole‐blood transfusions in 17 days. Salvage azacitidine (35 mg/m 2 subcutaneously for 5 days) plus venetoclax (360 mg/m 2 orally daily planned for 28 days) induced clinical remission, with notable improvements in appetite and activity, reduced transfusion dependence, and reduced splenomegaly, representing the first reported feline use of this combination. Toxicities were monitored with serial complete blood counts and Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events grading. Dose‐limiting Grade 4 neutropenia and thrombocytopenia and severe gastrointestinal toxicity with fever occurred during Cycle 2, prompting venetoclax discontinuation and hospitalisation for intensive supportive care and antimicrobials. Survival was 168 days from venetoclax initiation, supporting B‐cell lymphoma 2 inhibition as salvage, while highlighting cautious dosing and frequent monitoring.