Abstract
e19511
Background: Richter’s syndrome (RS) is a rare complication of chronic lymphocytic leukemia (CLL) and the median survival is generally poor. Evidence is limited regarding the biology of the disease, treatment and outcomes. Methods: We retrospectively reviewed pts diagnosed (dx) with pathologically confirmed RS who presented at the University of Miami Sylvester Cancer Center between 2011 and 2020. Informed consent was provided through IRB-approved protocols. Descriptive statistics were utilized and overall survival (OS) was calculated from RS diagnosis to death or last follow-up by Kaplan-Meier. Results: 33 patients with RS, including 87.9% diffuse large B-cell lymphoma-type RS and 12.1% Hodgkin lymphoma-type RS were identified. Median time from CLL dx to RS transformation was 37months (m). Most patients presented with elevated LDH 75%, bulky lymphadenopathy 66%, and adverse genetic features, such as TP53 disruption 52% or complex karyotype 81%. FISH at RS dx: del(17p) 37%, del(11q) 17%, trisomy 12 58%. ORR to first line therapy was 75.8% (55% CR, 27% PR), but of those who achieved CR, 44% relapsed. Median PFS (mPFS) was 10m for the anthracycline-based chemotherapy group (ABC) with a CR of 50%, compared to 15.5 m for the platinum-based chemotherapy group (PBC) and a CR of 60%. Similar OS were observed regardless of the chemotherapy regimen with median OS (mOS) of 60 m in the ABC group vs 59.5 m in the PBC group. Notably, the addition of a BTKi to chemoimmunotherapy lead to a mOS of more than 10 years in BTKi-naïve pts compared to 5.1 years in BTKi-exposed pts and 1.8 years in pts who did not receive a BTKi for RS treatment. Conclusions: Patients who develop RS often have high risk CLL, especially complex cytogenetics. Although a large proportion of pts with RS respond to frontline therapy, almost half relapse. While mOS is similar for anthracycline and platinum-based chemotherapies, platinum-based chemotherapy can lead to superior CR and PFS. BTKi-naïve pts who receive a BTKi with chemotherapy for RS treatment have superior mOS.