LAUSR

Dear Editor, As a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, venetoclax, in combination with low-dose cytarabine (LDAC) [1] or hypomethylating agents [2], was approved for the treatment of intensive chemotherapy-ineligible acute myeloid leukemia (AML). Bone marrow suppression, diarrhea, nausea, fatigue, and upper respiratory tract infections are common adverse events among patients treated with venetoclax-based regimens [3]. However, venetoclaxassociated skin manifestations are rarely reported. Here, we report an AML patient with complicated panniculitis after venetoclax treatment. A 57-year-old woman with a past medical history of hypertension, diabetesmellitus, and poliomyelitis was diagnosed with AML with multiple lineage dysplasia. The initial peripheral blood revealed leukocytosis (leukocyte count 12,120/mL, normal 4000 to 8000/mL) with excess blasts (46% of all nucleated cells). In addition, more than 40% of the bone marrow nucleated cells were myeloblasts, which were positive for myeloperoxidase and CD117 but negative for CD3 and CD79a. Cytogenetics showed normal karyotype. Genetic tests revealed mutations in BCOR, DNMT3A, KRAS, and IDH2; however, no NPM1 and FLT3 ITD mutations were identified. Considering the patient’s poor performance status, we treated her with venetoclax (400 mg/day in a 28-day cycle) and LDAC (20 mg/m/day from day 1 to day 10), according to the VIALE-C study [1]. After 9 days of treatment, multiple well-defined erythematous nodules with local heat and tenderness were observed over the posterior scalp (Fig. 1a), submandibular area (Fig. 1b), and right upper arm (Fig. 1c). No skin reactions were found over the subcutaneous injection sites of LDAC. The skin biopsy from her right upper arm showed panniculitis (Fig. 1d). No microorganism was identified in the biopsy specimen. Tissue culture did not demonstrate any pathogens. As the panniculitis was not responsive to topical steroids and systemic antibiotics treatment, we discontinued the drugs sequentially, and the skin lesions subsided naturally. For further AML treatment, we re-initiated the next cycle of venetoclax and LDAC. However, once again, a lesion appeared in the right arm that continued to deteriorate even after the LDAC was stopped. Further, we discontinued the venetoclax treatment. After stopping venetoclax, the skin lesion disappeared naturally. The AML was in complete remission after two incomplete cycles of venetoclax and LDAC.We allografted this patient from a matched sibling donor. Although previous studies have shown venetoclax-induced vitiligo and pruritus [4], venetoclax-induced panniculitis has not yet been reported. The pathophysiology of venetoclaxinduced panniculitis is unclear. Given the pathogenesis of subcutaneous panniculitis–like T cell lymphoma [5], the survival advantage of effector T cells following BCL-2 inhibition may be responsible for venetoclax-induced panniculitis [6]. IDH2 mutation could be another possibility causing panniculitis in this patient since IDH2 inhibition can induce differentiation syndrome in AML [7]. Although the leukemic cells harbored IDH2 mutations, unfortunately, we did not examine the mutations in cells infiltrating the panniculitisaffected regions. Further studies are required to identify the mechanisms of venetoclax-induced panniculitis. * Chieh-Lin Jerry Teng [email protected]