Richter syndrome epidemiology in a large population based chronic lymphocytic leukemia cohort from Norway

Background: Transformation to aggressive lymphoma (Richter syndrome, RS) occurs in a substantial subset of patients who must discontinue targeted therapy for chronic lymphocytic leukemia (CLL). RS has an extremely poor prognosis. Methods: Using the nation-wide database of The Cancer Registry of Norway of 7664 CLL patients registered between 1953-2012, we identified 107 patients experiencing RS. Results: Seventy seven (72%) of RS patients were identified among 2631 CLL patients diagnosed between 2003-2012; diffuse large B-cell lymphoma (DLBCL) was identified in 65 (84%), Hodgkin lymphoma (HL) in 12 (16%) patients and the diagnosis was confirmed in 50 (65%) available biopsy specimens. The incidence rate in this period was 4.7/1000 person-years (95% CI: 3.8-5.9). The median survival from CLL diagnosis was 1.7 years (95% CI: 0.34-2.3) for RS patients while it was 10.3 years (95% CI: 9.5-10.9) for the remaining CLL patients. Male gender predominated among RS patients (69%) compared to CLL population (58%) and RS patients were diagnosed with CLL at a significantly younger age than the remaining patients (65 vs. 72 years). Median time from diagnosis of CLL to RS was 2 years (Range, 0-13 years). No CLL treatment was administered in 25 (33%) patients prior RS diagnosis; a median of 1 treatment line was administered to pretreated patients. The median duration of survival after RS diagnosis was 27 months (95% CI; 9-88). Conclusions: Collectively, RS was a rare complication of CLL in the chemoimmunotherapy era, occurred early in the CLL course in younger, and both treatment naive and pretreated patients, and shortened survival substantially.