Development of Richter's transformation in a patient with refractory chronic lymphocytic leukaemia on ibrutinib therapy
Abstract
Modern oral inhibitors of B-cell receptor signalling pathways such as ibrutinib and idealise and the bcl-2 inhibitor venetoclax represent effective treatment options in patients with relapsed/refractory chronic lymphocytic leukaemia (CLL). Richter's transformation (RT, progression of CLL to aggressive lymphoproliferation, most commonly diffuse large B-cell lymphoma, DLBCL) is usually a prognostically highly adverse event with limited treatment options and very short survival, especially when RT occurs on treatment with one of the new inhibitors.
We present a case report of RT developing in a 58-year-old CLL patient who relapsed following allogeneic stem cell transplantation treated with ibrutinib. After 11 months on ibrutinib therapy, the patient experienced progression in the form of massive intraabdominal lymphadenopathy.
Positron emission tomography/computed tomography (PET/CT) revealed significant hypermetabolism of glucose in the abdominal mass. A needle biopsy was performed and histology confirmed DLBCL.
The patient was treated with R-CHOP chemoimmunotherapy and subsequently with R-GD (rituximab, gemcitabine, dexamethasone) because of R-CHOP resistance. However, active anti-lymphoma therapy had to be terminated because of severe thrombocytopenia.
The therapeutic approach was changed to symptom management and the patient died in a hospice 2.5 months after diagnosis of RT. In conclusion, this case report demonstrates the extremely unfavourable prognosis of Richter's syndrome arising on ibrutinib therapy in a patient with advanced CLL.