Real-world characteristics, treatment patterns, and outcomes of patients with 2 or more LOTs for CLL/SLL in the US

• Targeted agents have revolutionized CLL/SLL treatment, shown by decreased use of CIT and increased use of BTKis and BCL2s from 2014-2023.

• Median times to events were generally shorter for each subsequent LOT. Unmet need persists among second and later line patients with CLL.

The development of targeted agents for CLL/SLL has transformed the treatment paradigm for patients with CLL. Due to this evolving treatment landscape, there was a need for contemporaneous evidence related to US treatment patterns and outcomes among patients treated in the real-world. Using COTA’s EHR-based database, we examined characteristics, treatment patterns, and outcomes of patients receiving 2L+ by LOT. 1,283 adult CLL/SLL patients were identified in the dataset who initiated 2L between 1/1/2014 and 6/30/2022. Of those patients, 542 patients (42.2%) later received 3L therapy, of whom 228 (42.1%) went on to receive 4L therapy. More than 18% of patients died after 2L initiation and prior to 3L initiation, and more than a quarter died prior to 4L initiation. The majority of the population was White (77.7%), male (60.6%), 65 years old or greater (68.8%), and treated in a community practice setting (87.8%). Regarding treatment patterns, from 2014 to 2023, utilization of CIT in any 2L+ LOT decreased, while utilization of BTKi and BCL2-inhibitor therapy increased. Across endpoints, median times to event(s) were generally shorter with each subsequent LOT received both in the overall population and among patients receiving a given therapy in different LOTs. With a median follow-up time from 2L initiation of 38.0 months, median rwTTNT, rwPFS, and rwOS from 2L was 31.9, 33.8, and 80.1 months, respectively. Despite great advancements in CLL/SLL treatments since 2014, unmet need persists for patients receiving late line therapy.