Pseudo-Richter transformation in a patient with chronic lymphocytic leukemia after cessation of fixed duration venetoclax/ibrutinib treatment.

Pseudo-Richter transformation (Pseudo-RT) in chronic lymphocytic leukemia (CLL) refers to rapid clinical progression resembling Richter transformation (RT), DLBCL - type. It presents with systemic symptoms and lymphadenopathy. Distinguishing Pseudo-Richter from true Richter transformation is challenging but clinically essential due to differences in prognosis and treatment approaches. A 69-year-old Caucasian man was diagnosed with symptomatic CLL. Treatment was initiated with ibrutinib (cycles 1-15) and venetoclax (cycles 4-15). The patient responded well, with clinical and hematological complete response. One week after the last cycle was completed, the patient developed fever, abdominal pain, and recurrent lymphadenopathy. Imaging revealed partial regression and new progression of lymph nodes, splenic infarction, and an eventual splenic rupture requiring emergency splenectomy. Histology showed a diffuse infiltrate of large cells and paraimmunoblasts with high proliferation index (~ 50%), raising suspicion of RT. However, molecular testing was negative for typical findings of high-grade lymphoma and PET-CT did not support it as well. Suspecting pseudo-RT ibrutinib was reintroduced 14 days after cessation, leading to rapid normalization of leukocyte counts and clinical improvement. We report a case of pseudo-RT in a CLL patient treated with ibrutinib/venetoclax combination therapy, contrasting prior reports involving Bruton tyrosine kinase inhibitor (BTKi) monotherapy. The rapid onset of transformation-like symptoms following recent BTKi interruption/cessation should raise suspicion for pseudo-RT, though true RT must be excluded. As BTKi use in CLL increases, this phenomenon may become more common. Prompt interdisciplinary collaboration is essential for accurate diagnosis and appropriate management. Further research is needed to develop rapid diagnostic tools to distinguish pseudo-RT from true RT.