Richter syndrome (RS) is typified by the emergence of an aggressive lymphoma in individuals who have been previously or simultaneously diagnosed with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Although it is relatively rare, appearing in 2% to 10% of CLL patients, RS often proves to be lethal due to its rapid progression and the scarcity of specific therapies. Venetoclax, a BCL2 inhibitor, has demonstrated efficacy in CLL but its role remains less explored in RS. Hence, there is a paucity of information regarding the direct employment of Venetoclax in the treatment regimen for RS. This study presents a case of Richter transformation being managed under treatment with Venetoclax.

A 51-year-old female patient, diagnosed with CLL with negative 17p deletion following investigations in 2015 due to autoimmune immune thrombocytopenia (ITP) and lymphocytosis, was given 6 cycles of FCR (fludarabine, cyclophosphamide, rituximab) due to steroid-resistant autoimmune thrombocytopenia, and complete response (CR) was achieved according to iwCLL criteria. After remission, the patient was monitored without treatment, and in 2020, full blood count, biochemical analysis, and peripheral smear were performed due to fatigue symptoms. The complete blood count showed leukocytes: 44600/mm3, lymphocytes: 39000/mm3, MCV: 86 fl, and hemoglobin: 9.5 g/dL. The patient, with no signs of hemolytic anemia, had no nutritional (Fe, B12, folate) deficiency, and normochromic normocytic anemia was detected. There were no mutations in the immunoglobulin heavy chain variable region (IGHV) genes. The patient, evaluated as relapsed stage 3 disease, was started on venetoclax-rituximab treatment.

In the 11th month of the treatment, due to symptoms of fatigue, fever, night sweats, and weight loss, a bone marrow biopsy was performed after pancytopenia was observed, and a diagnosis of diffuse large B-cell lymphoma was made. Due to Richter transformation, DA-R-EPOCH (dose-adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin) treatment was initiated. After 4 cycles of DA-R-EPOCH treatment, single-agent ibrutinib was started due to treatment-resistant disease and an ECOG performance score of 2. The patient, whose disease continued to progress under ibrutinib treatment, died from septic shock.

This case underscores the complexities in treating Richter syndrome, particularly with venetoclax, and emphasizes the need for careful monitoring and understanding of potential transformations. The development of Richter transformation under venetoclax treatment highlights an area that requires further investigation and consideration in the management of CLL. Prospective studies and a comprehensive approach are vital to enhancing treatment strategies and improving outcomes for patients with this aggressive form of lymphoma.