1109 - Real world treatment patterns, reasons for discontinuation, and survival outcomes among patients with chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) receiving second or later lines of therapy in a contemporary population treated in the United States

Introduction: The development of targeted agents has transformed the treatment paradigm both in the first-line (1L) setting and for previously treated patients with CLL/SLL. This study examines the characteristics, treatment patterns, and outcomes of a large cohort of real-world patients receiving 2L or later lines of therapy (LOTs) by LOT.

Methods: Patients meeting the following criteria were identified from the COTA real-world database: Aged ≥ 18 years at diagnosis with a confirmed CLL/SLL diagnosis who initiated 2L therapy between January 1, 2014 and June 30, 2021. Patients were ineligible if they had a documented diagnosis of a concurrent primary malignancy or transformation at the time of CLL/SLL diagnosis or a history of other primary malignancies, excluding benign skin cancers, within 3 years prior to CLL/SLL diagnosis. The initial index date for the study was the date of initiation of 2L therapy and was updated to the start of each subsequent LOT for LOT-specific analyses. The observation period was defined as the duration of time from index date to the date of patient death or last visit date (if date of death was not available). Patient and clinical characteristics and treatment patterns were summarized as appropriate using means, medians, and/or patient counts and percentages. Clopper-Pearson exact method was used for presenting confidence intervals for proportions. Time to event outcomes, including real-world progression-free survival (rwPFS) and real-world overall survival (rwOS), were assessed for the study population and by LOT using the Kaplan-Meier method.

Results: A real-world population of 1,102 eligible patients with the following characteristics were included in the study: median age at diagnosis of 64 years (IQR: 57, 72), median age at 2L initiation of 70 years (IQR: 63, 78), male (60.9%), Caucasian (83.0%), and treated in the community setting (88.1%) (Table 1). Patients were most commonly diagnosed in 2014 or earlier (74.1%). Among patients with test results for the given molecular marker, marker positivity included: 59% (Nf314/536) del(13q), 35% (Nf135/385) del(11q), 23.1% (Nf86/372) del(17p), 20.6% (Nf102/496) TP53, and 32.3% (Nf70/217) IGHV mutated.

The most common treatments among patients receiving 2L therapy were ibrutinib, bendamustine + rituximab (BR), rituximab, acalabrutinib, and investigational regimen (Figure 1). In 3L, the most common regimens were ibrutinib (26.1%, Nf122), acalabrutinib (10.7%, Nf50), and BR (10.0%, Nf47), and among patients who received 4L, common regimens included ibrutinib (21.9%, Nf44), rituximab + venetoclax (10.4%, Nf21), and acalabrutinib (9.5%, Nf19). Utilization of BTK and BCL2 inhibitors and anti-CD20 antibodies increased from 2014 (39.9%, 0.0%, and 9.2%, respectively) to 2022 (48.9%, 34.0%, and 25.5%, respectively), while utilization of chemoimmunotherapy decreased markedly over the same time period (from 37.9% to 6.4%).

Regarding reasons for treatment discontinuation, patients receiving 2L BTKi therapy discontinued therapy primarily due to toxicity (47.3% [Nf115/243] among patients receiving ibrutinib and 40.0% [Nf8/20] among patients receiving acalabrutinib) or death (14.0% [Nf34/243] among patients receiving ibrutinib and 20.0% [Nf4/20] among patients receiving acalabrutinib). CLL disease progression and doctor preference were also common reasons for treatment discontinuation in 2L. Approximately 17% of patients died after initiating 2L and prior to initiating 3L, and 25.5% of patients died prior to initiation of 4L. Among the study population, median rwPFS from initiation of 2L was 31.4 months (95% CI: 28.6, 35.5) and median rwOS from initiation of 2L was 79.0 months (95% CI: 68.9, 85.3).

Conclusions: Although targeted therapies have improved the outcomes of patients with CLL/SLL, these analyses suggest that there is still an unmet need with a high proportion of patients discontinuing treatments due to progression or toxicity. Furthermore, 2L+ patients continue to experience poor survival outcomes. Innovative treatment options and novel mechanisms of action are needed to improve CLL patient outcomes.