Venetoclax-Treated Patient With CLL: Richter’s Transformation as Leptomeningeal Infiltration
Posted: Wednesday, June 16, 2021
Maria Dimou, MD, PhD, of the National and Kapodistrian University of Athens, and colleagues described a unique case of Richter’s transformation presenting as leptomeningeal infiltration by high-grade B-cell non-Hodgkin lymphoma in a patient with chronic lymphocytic leukemia (CLL) who was treated with venetoclax. This patient profile, which was published in the journal Clinical Case Reports, raises the question of whether the blood‐brain barrier could be a “sanctuary” during treatment with this BCL2 inhibitor.
A 56-year-old woman with asymptomatic CLL developed autoimmune hemolytic anemia, which was successfully managed. However, she subsequently experienced splenomegaly and lymphadenopathy. Mutational analyses detected an unmutated variable heavy-chain sequence. Progressive disease was reported after 3 months of treatment with rituximab plus chlorambucil. After receiving fludarabine plus cyclophosphamide and rituximab, she achieved partial remission.
Progressive disease with splenomegaly, lymphadenopathy, and thrombocytopenia occurred 48 months after chemotherapy. The patient received ibrutinib before switching to idelalisib plus rituximab. Initially, splenomegaly and lymphadenopathy seemed to improve; however, after 6 months, she experienced progressive disease. The bone marrow karyotype was complex. The patient was administered 400 mg of venetoclax daily. When the reactivation of autoimmune hemolytic anemia was noticed, she received corticosteroids and cyclosporine. As a result, treatment with venetoclax was discontinued; however, it was eventually reinitiated at a dose of 200 mg daily due to CYP3A inhibitor interactions. Further dose reduction to 100 mg daily occurred after she presented with grade 4 neutropenia. There seemed to be adequate control of CLL.
At 20 months after initiation of treatment with venetoclax, the patient developed walking and speech difficulties. The reappearance of splenomegaly was noted. Analyses of cerebrospinal fluid revealed monomorphous large, cerebriform lymphoid cells with nucleoli; the immunophenotype showed a large clonal B lymphoid population. In addition, the investigators found an unmutated variable heavy-chain sequence, which seemed to be identical to that of the diagnosis sample. High-dose dexamethasone was administered, followed by an intrathecal infusion of dexamethasone plus methotrexate; however, the patient died in a coma.
Disclosure: The study authors reported no conflicts of interest.
