Treatment Patterns and Economic Burden Among US Patients with Richter's Syndrome: A Retrospective Claims Analysis
Authors: Garg Mahek , Satija Ambika , Song Yan , Meade Ben , Signorovitch James , Gandra Shravanthi 
Published: December 2024

BACKGROUND: Richter's syndrome (RS) is a rare and aggressive transformation of chronic lymphocytic lymphoma (CLL) with poor prognosis in most patients. There is a lack of real-world research on the treatment landscape and economic burden of RS.
AIMS: To assess treatment patterns, healthcare resource use (HRU), and costs among patients with RS in the US.
METHODS: An algorithm was used to identify RS as it has no distinct diagnosis codes. Adult patients with ≥2 diagnosis codes for CLL on distinct dates within 12 months, followed by ≥2 diagnosis codes for any lymphoma on distinct dates within 12 months were identified in Optum's de-identified Clinformatics® Data Mart Database during 10/1/2015-6/30/2021. The first diagnosis for lymphoma was defined as the index date. Patients were required to have no diagnosis codes for lymphomas in the year pre-index, have ≥12 months continuous enrollment pre-index (i.e., baseline period), and ≥1 month continuous enrollment post-index. Patients with any malignancy in the year pre-index were excluded. Demographic and clinical characteristics were assessed during baseline. The study period spanned from index through end of continuous enrollment or data. A line-of-therapy (LOT) algorithm was used to identify first (1L), second (2L), and third (3L) line treatments in a subsample with no claims for treatments of interest in baseline and ≥1 claim for treatments in the study period. All-cause and RS-related HRU in terms of monthly incidence rates and 95% confidence intervals (CI) and per patient per month (PPPM) costs were described over the study period. HRU and costs were additionally described during 1L, 2L, and third and subsequent line (3L+) periods.
RESULTS: A total of 1,701 patients with RS were followed for a mean of 27 months. Patients had a mean age of 73 years, 60% were male, and 82% were covered by Medicare Advantage. Mean National Cancer Institute Comorbidity Index was 2.2, with cardiovascular disease (34.7%), diabetes (28.5%), and chronic obstructive pulmonary disease (26.7%) being the most common comorbidities. The treatment pattern analysis included 563 patients, of which 33.4% had 2+ LOTs. In 1L, bendamustine-based therapies (29.3%), rituximab monotherapy (18.3%), and ibrutinib-based therapies (17.4%) were most commonly used. In both 2L and 3L, the most common treatment regimens were ibrutinib-based therapies (32.4% and 18.4%, respectively) and rituximab monotherapy (19.7% and 18.4%, respectively). Mean treatment duration (days) decreased from 1L (183) to 3L (130). Patients had 0.10 all-cause inpatient (IP) visits, 2.87 outpatient (OP) visits, and 0.05 emergency room (ER) visits PPPM. Less than half of all-cause visits were RS-related. Total all-cause costs were $16,421 PPPM, driven largely by medical costs ($14,791 PPPM), especially RS-related medical costs ($9,453 PPPM). Roughly 80% of RS-related medical costs were due to IP visits. In general, all-cause and RS-related HRU and costs increased by LOT. For instance, total all-cause costs increased from $16,582 in 1L to $26,276 in 3L+, with medical costs constituting a large portion of total costs across lines, and both all-cause and RS-related IP costs more than doubling from 1L to 3L+. The only exception was OP costs, which were highest in 1L.
CONCLUSION: This study describes real-world treatment patterns and economic burden for RS in the US. Results show that combination therapies that include bendamustine and ibrutinib, as well as rituximab monotherapy are commonly used to treat RS. This study also demonstrates the high economic burden in RS, which increases with subsequent LOTs, highlighting an important area of unmet need.