Does Venetoclax Cause Vitiligo?

Abstract

Introduction: Venetoclax is a highly selective, orally bioavailable BCL2 inhibitor which binds to the BH3 domain of BCL2, displacing proapoptotic proteins such as BIM and BAX that once released facilitate induction of apoptosis. Venetoclax is indicated for the treatment of patients with newly-diagnosed acute myeloid leukemia (AML) who are 75 years or older or have other medical conditions that prevent the use of standard chemotherapy. There are many side effects associated with use of venetoclax. Vitiligo has not been reported as a side effect of Venetoclax. We are presenting a case of vitiligo induced by Venetoclax in a patient with AML. Case description: 71-year-old Caucasian female with ECOG performance status of 2, presented to Hematology/oncology clinic for evaluation for persistent thrombocytopenia. Past medical history is significant for hypothyroidism, essential tremor and chronic fatigue and weakness. Review of systems revealed fatigue, generalized weakness, easy bruising, tremors and weight loss of 10 pounds in 6 months. She denied any fevers, chills, gross bleeding. or any other systemic symptoms. Family history is significant for sarcoma (father). Denied any smoking, alcohol or illicit drug use. Vitals were stable. Physical examination revealed bruising on both arms and legs. Initial laboratory data showed hemoglobin of 10.7, White blood cell count of 3000 with 43% lymphocytes, and platelet count of 15000. Flow cytometry showed 17% blasts and Bone marrow biopsy revealed AML, non-APL type with 30 % blast cells. Karyotype 46, XX. FISH did not reveal any of the common abnormalities observed in MDS. Molecular analysis showed no abnormalities in FLT-3, IDH1/IDH2, NPM1 or CEBPA. Given her performance status, she was not considered a candidate for intense chemotherapy. She was started on low dose cytarabine 20 mg/m2 SQ QD from days 1 to 10 every 28 days with venetoclax 100 mg PO q daily titrated up to 600mg per day. Venetoclax was discontinued on day 10 of treatment due to neutropenia, diarrhea and fatigue. Bone marrow biopsy after one cycle of treatment showed a complete response. Cytarabine was discontinued due to poor tolerability and venetoclax was restarted at 200mg per day. 6 weeks after restarting venetoclax, she developed a mildly painful erythematous macular rash, initially noted in her hands but then extending to neck and chest. The rash then became hypochromic. She was evaluated by dermatology and diagnosed with venetoclax induced Vitiligo. Venetoclax was discontinued secondary to recurrent diarrhea and pancytopenia and then restarted at 100mg per day after recovery from pancytopenia. There was complete resolution of the vitiligo during discontinuation of venetoclax, with recurrence shortly after reinitiating the medicine. She was treated with topical corticosteroids and kept on venetoclax. Discussion: Venetoclax is a selective small-molecule inhibitor of BCL-2, an antiapoptotic protein. It is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and newly diagnosed AML in patients who are not candidates for intense chemotherapy. Adverse events associated with venetoclax include pancytopenia, electrolyte abnormalities, fatigue, edema, tumor lysis syndrome, increases serum AST, diarrhea, upper respiratory infections, fever and rash. To our knowledge, this is the first reported case of vitiligo induced by venetoclax. Skin reactions, including vitiligo should be considered as potential side effects of this medication. Figure Disclosures No relevant conflicts of interest to declare.

Pityriasiform drug eruption associated with venetoclax for acute myeloid leukaemia

“…While there have been scattered reports of ‘rash’ and ‘pruritus’ associated with venetoclax therapy, few analyses have included morphological clarification [8]. Isolated case studies have reported venetoclax-associated vitiligo [9,10], panniculitis [11], geographic tongue [12] and disseminated varicella zoster virus [13], respectively. On the other hand, no maculopapular drug eruptions have been described.…”

Venetoclax-induced vitiligo in a patient with chronic lymphocytic leukemia

“…However, shortly after the drug was re-introduced, she developed vitiligo again. She was treated with topical corticosteroids and kept on venetoclax [19]. In the present case, a decision was made to continue venetoclax and monitor vitiligo closely given the low severity, and the vitiligo not affecting the activities of daily living or causing psychological stress.…”