Yang, Keri

Abstract Introduction Bruton tyrosine kinase inhibitors (BTKis) have changed the treatment algorithm for patients with high-risk relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Efficacy was demonstrated for zanubrutinib and ibrutinib in high-risk R/R CLL patients in the ALPINE (NCT03734016) trial, for ibrutinib and acalabrutinib in the ELEVATE-RR (NCT02477696) trial, and for acalabrutinib in the ASCEND (NCT00135226) trial. While there is limited head-to-head comparative trial data of all covalent BTKis in the treatment of high-risk R/R CLL, a previously published network meta-analysis (NMA) used data from the ALPINE, ELEVATE-RR, and ASCEND trials, and reported that zanubrutinib demonstrated significantly improved relative efficacy compared to ibrutinib and acalabrutinib in high-risk R/R CLL (Shadman 2025). Within this NMA, high-risk R/R CLL populations were defined based on the prespecified definitions within each trial, including patients with del(17p) and/or TP53 mutations in the ALPINE and ASCEND trials, and del(17p)/del(11q) in the ELEVATE-RR trial. This study aimed to compare zanubrutinib versus ibrutinib and acalabrutinib in high-risk R/R CLL by calculating the number needed to treat (NNT) to avoid one progression or death. Methods A model was developed to evaluate the NNT among high-risk R/R CLL patients to avoid a progression or death. Progression free survival (PFS) data for zanubrutinib in high-risk patients were extracted from the ALPINE trial. PFS values for ibrutinib and acalabrutinib were derived from the previously published NMA study. PFS for ibrutinib and acalabrutinib were calculated by applying PFS hazard ratio from the NMA results to the zanubrutinib PFS value for the high-risk population in the ALPINE trial. 24-month PFS (72.6% for zanubrutinib, 52.0% for ibrutinib, and 55.9% for acalabrutinib) were used for the base case analysis of the model. Sensitivity analyses were conducted to examine the impact of alternative PFS inputs for ibrutinib, derived directly from the high-risk populations in ALPINE trial (unadjusted). Results The base case results from the NNT model indicate that for the treatment of patients with high-risk R/R CLL over 24-months, every five patients treated with zanubrutinib instead of ibrutinib results in the avoidance of one disease progression or death and every six patients treated with zanubrutinib instead of acalabrutinib results in the avoidance of one disease progression or death. Applying the model result to a hypothetical scenario of 100 patients with high-risk R/R CLL treated with zanubrutinib versus ibrutinib for two years finds approximately 20 patients will avoid disease progression events or deaths. Treating the same population with zanubrutinib versus acalabrutinib for two years will result in the avoidance of 17 disease progression events or death. Sensitivity analysis showed consistent NNT results.Conclusions The NNT analysis suggests that among high-risk R/R CLL patients, zanubrutinib is associated with more favorable clinical outcomes compared to ibrutinib and acalabrutinib. Over 24 months, zanubrutinib demonstrated a NNT of five to prevent one disease progression or death compared to ibrutinib, and an NNT of six compared to acalabrutinib, in high-risk R/R CLL patients. Study findings should be interpreted based on modeling assumptions and potential patient population differences across trials.

Abstract Introduction: CLL disease control and survival outcomes have improved since the introduction of Bruton tyrosine kinase inhibitors (BTKis). Since CLL often requires treatments, understanding patient preferences is critical in optimizing adherence and overall satisfaction. However, there are limited published data on how Korean patients prioritize treatment efficacy, safety and the convenience of administration. To address this gap, a discrete choice experiment (DCE) methodology was applied in a comprehensive quantitative analysis to evaluate patient preferences for BTKi treatment attributes among patients with CLL in Korea. Methods: Adult patients (≥18 years of age) with a confirmed diagnosis of CLL in Korea were recruited by The Korea Blood Disease & Cancer Association to participate in an online DCE survey questionnaire from April 30, 2025 to May 22, 2025. Treatment attributes and levels were identified based on published literature and clinical inputs. Efficacy attributes included progression-free survival (PFS); safety attributes included impacts of adverse events (AEs), including diarrhea, headache, atrial fibrillation and hypertension, on quality of life (QoL); convenience attributes included formulation type (including tablet or capsule) and dosing frequency (including once daily or twice daily). Preference data was analyzed using a conditional logistic regression. Relative importance of BTKi treatment attributes were calculated to measure the importance of each attribute in treatment decision-making. Additionally, subgroup analyses were conducted among patients aged <60 years and ≥60 years, those who received 2 or more lines (2L+) of treatments, and those who experienced AEs from CLL treatment. Results: A total of 57 patients completed the survey. The mean age was 61 years, with 46% aged <60 years and 54% aged ≥60 years. Female patients comprise 35% of the sample. Around 33% had a high school education or less, and 23% were employed full-time. More than half (54%) reported no comorbid conditions, and 70% were diagnosed ≥5 years ago (26% diagnosed 1 to <5 years ago; 4% diagnosed less than a year ago). In terms of treatment experience, 11% were treatment naive, while 89% received ≥1 treatment (61% first-line, 21% second-line and 7% third-line or later). In the context of CLL treatment preferences, patients showed a significant preference (P < .05) for therapies that minimized the impact of AEs on QoL, offered longer PFS, and required less frequent dosing. Formulation type did not have a statistically significant impact on treatment choice. Overall, patients placed greater importance on how treatment-related attributes affect their QoL and dosing frequency. The highest-ranked factors were the impact of headache (22%) and diarrhea (21%) on QoL, followed by dosing frequency (19%), the impact of atrial fibrillation (16%) and hypertension (14%) on QoL, PFS (7%), and formulation type (0.6%). Results from the subgroup analyses were generally consistent with the full sample analysis, with impacts of AEs on QoL being the most important factors for treatment decision-making, especially among older patients, although the relative ranking of impacts of AEs varied by age groups and treatment experience. Regarding efficacy, younger patients (<60 years of age) valued PFS slightly more than older patients (≥60 years of age), ranking it 4th and 6th out of the 10 attributes, respectively. Additionally, preference on dosing frequency was more important for 2L+ patients, reflecting the treatment burden experienced from previous regimens. Conclusions: This study provides valuable insights into the treatment preferences of Korean patients with CLL, highlighting the importance of QoL considerations for treatment decision-making. Among the evaluated attributes, patients placed the greatest weight on minimizing the impacts of AEs, particularly headache and diarrhea, on daily functioning, followed by dosing frequency. These preferences underscore the need for patient-centered care that prioritizes not only clinical efficacy but also tolerability and convenience. These insights can inform shared decision-making and support the development of personalized treatment strategies that better align with patient needs and expectations in Korea.

e19033 Background: CLL tends to affect older individuals, and older patients often endure greater health disparities and treatment burdens that may impact their access to healthcare resources, adherence to treatment regimens and treatment outcomes (UN, Health Inequalities in Old Age). This study aimed to assess treatment utilization patterns, discontinuation, and healthcare resource utilization (HCRU) of 1L use of BTKi in CLL, focusing on older patients ≥65 years (yrs). Methods: A retrospective observational study using the Symphony Integrated Dataverse was conducted to identify adult CLL patients initiating a 1L BTKi (zanubrutinib [ZANU], acalabrutinib [ACA] or ibrutinib [IBR]) treatment regimen from 02/2022 and 09/2024 (index period). Patients were required to have ≥30 days of continuous enrollment in the pre- and post-index periods. Patients initiating a BTKi were further categorized by age at index date. Patient sociodemographic, clinical characteristics, and outcomes were reported in overall and older (≥65 yrs) CLL patients by each BTKi group. Treatment discontinuation rate was examined at 60, 90, 120, 150, 180, and 360 days, and by median time to discontinuation (TTD), estimated using the Kaplan-Meier method, censoring patients at the end of follow-up. HCRU (outpatient, inpatient, and other services) was evaluated during time on treatment and over the follow-up period and reported as per-patient-per-year (PPPY). Results: A total of 6,846 patients initiated a 1L BTKi (ZANU: n=1,853; ACA: 3,519; IBR: 1,474) for CLL during the index period. Patients receiving ZANU were older (mean age: 70.9 yrs; 78% ≥65 yrs) than those receiving ACA (69.4 yrs; 71% ≥65 yrs) and IBR (69.6 yrs; 73% ≥65 yrs). Payer type and geography were significantly different across each BTKi group ( p <.001). There were no significant differences across the BTKis regarding baseline comorbidities. ZANU patients had the longest estimated median TTD overall (ZANU: 18.9 months [m], ACA: 17.8 m, IBR: 14.5 m; p <.001) and in patients ≥65 yrs (ZANU: 17.2 m, ACA: 15.2 m, IBR: 12.6 m; p <.001). ZANU patients also had the lowest estimated discontinuation rates at 60- , 90-, 120-, 150-, 180-, and 360-days post BTKi initiation in the overall and ≥65 yrs groups. There were significant differences across the BTKi group for inpatient visits PPPY in all patients and ≥65 yrs with ZANU having the lowest visits of the BTKis (ZANU: 2.6, ACA: 3.6, IBR: 4.6; p =.029 and ZANU: 2.5, ACA: 4.3, IBR: 5.3; p =.004, respectively). Conclusions: This real-world study demonstrated that CLL patients treated with ZANU had longer TTD, lower discontinuation rates, and less HCRU than ACA and IBR across all patients and specifically in older patients ≥65 yrs. Further studies on long-term and clinical outcomes are warranted.

Introduction: The prognosis for CLL/SLL has improved with the advent of novel therapeutic classes, including BTKis. While comparative data for several BTKis have been published, there are limited data on patient preferences in BTKi treatment selection. Understanding and integrating patient perspective in the BTKi treatment selection process is crucial to shared decision-making and attaining optimal treatment outcomes. To understand patients' priorities for different treatment attributes that impact their treatment decisions, a comprehensive quantitative analysis of patient preferences on BTKi treatment attributes was conducted. Methods: A patient survey with a discrete-choice experiment (DCE) design was conducted from March to June 2024 among USA adults (≥18 years) with confirmed diagnosis of CLL/SLL, recruited through online patient panels, physician referrals, and support groups. BTKi treatment attributes were selected based on results of a targeted literature review and clinical inputs. Patients responded to DCE questions on attributes related to efficacy, safety (eg, impacts of diarrhea, headache, atrial fibrillation, and hypertension on quality of life [QoL]), formulation type, and dosing frequency. The impact of adverse events (AEs) on QoL was defined as the extent to which AEs caused interruptions in patients' ability to engage in their usual day-to-day activities. A conditional logistic regression model was used to calculate the relative importance of each attribute, as well as patient willingness to trade off specified BTKi treatment attributes. Results: A total of 200 patients with CLL/SLL completed the survey (median age: 61 years; 78% White; 55% female; 60% commercially insured; 82% suburban/urban residence). Less than half (43%) were diagnosed ≥5 years ago, and 61% received ≥3 lines of therapy. Almost all (89%) patients reported having experienced ≥1 AE from treatment previously, with the most common AEs being fatigue (76%), diarrhea (51%), headache (51%), and nausea and/or vomiting (51%). When considering the importance of efficacy measures, most patients prioritized CLL/SLL treatments that extended life expectancy (93%), followed by those that increased the likelihood of remission or cure (84%) and those that paused the progression of disease (67%). Patients preferred treatments with higher efficacy, less impact of AEs on QoL, and lower dosing frequency (P&lt;.001). The top 3 treatment attributes with the highest relative importance to patients were impact of atrial fibrillation on QoL (24%), progression-free survival (PFS; 19%), and impact of headache on QoL (18%), followed by impact of diarrhea (14%) and hypertension (14%) on QoL, dosing frequency (9%), and formulation type (3%). On average, patients were willing to accept a reduction of 2.6, 1.9, 1.4, and 1.4 years of PFS to receive a treatment with less (none or mild vs significant) impact of atrial fibrillation, headache, diarrhea, and hypertension on QoL, respectively. Patients were willing to accept a reduction of 1.0 year of PFS to receive once-daily vs twice-daily treatment. Conclusions: Findings from this patient preference survey suggested that impact of atrial fibrillation on QoL, PFS, and impact of headache on QoL were the most important attributes of BTKi treatment for patients with CLL/SLL in the USA. Shared decision-making in CLL/SLL treatment selection should include an informed discussion about AEs, as besides efficacy comparisons, patients may prefer treatments with less impact of AEs on their QoL. Future prospective studies evaluating the effects of shared treatment decision-making on treatment adherence and outcomes are needed to better understand their impact on CLL/SLL patient care and inform clinical practice.

e19049 Background: Acala and zanu are 2nd generation Bruton tyrosine kinase inhibitors (BTKis) that have demonstrated improved safety profiles vs 1st generation BTKi ibrutinib in clinical trials. While head-to-head comparison of zanu vs acala is lacking, a recent meta-analysis of clinical trials provided a comprehensive, indirect comparison of the AE profiles in B-cell malignancies (Hwang, Hemasphere. 2023;7(S3):1134). This study aims to evaluate costs and impacts on quality of life (QoL) for zanu vs acala using their AE profiles. Methods: A health economic model was developed to determine cost and QoL associated with AE management for zanu and acala. The incidence rates ( IRs) of all grade and grade ≥3 AEs of interest (n=21, including bleeding events, hypertension, atrial fibrillation, cytopenias, infections, headache, arthralgia, diarrhea) were taken from the meta-analysis. Additional model inputs, such as disutility, average duration of AE, and unit cost of each AE were sourced from published literature and publicly available cost databases in consultation with clinical experts. The model was developed from the US perspective, considering Medicare costs, inflated to 2023 USD. Model outcomes were AE management cost (= IR * unit cost) and quality-adjusted life years (QALYs) lost due to AE (= IR * Disutility * Duration/365.25). Results: In the base-case scenario (considering all AEs), treating a hypothetical cohort of 1000 patients (pts) with zanu instead of acala yielded cost savings of $124K and 3.7 QALY gains (i.e., 3.7 years extra in full health). Subgroup analysis for severe (grade ≥3) and non-severe AEs (grade 1-2) demonstrated similar trends. A sensitivity analysis limited to AEs significantly different between zanu and acala (n=13) yielded consistent results. Additionally, a probabilistic sensitivity analysis, conducted with 1000 iterations to account for uncertainty in model parameters, confirmed robustness of the model, indicating stable conclusions across a wide range of parameter uncertainties. Conclusions: This analysis suggested that zanu is cost-saving and associated with added health benefits compared to acala in terms of AE management in pts with B-cell malignancies. Should these results derived from meta-analysis of clinical trial data be applicable to real-world pt populations across different indications, the potential cost savings could be considerable. These results could be further improved if the differences in efficacy of zanu vs acala are also incorporated. [Table: see text]

7072 Background: LG-NHL is mostly incurable, imposing a prolong impact of cancer care burden for pts. This study aimed to quantify the burden of MH conditions in pts with newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), or marginal cell lymphoma (MZL). Methods: A retrospective study was conducted using Optum Clinformatics Data Mart to identify pts ≥18 years with ≥1 new diagnosis for CLL, FL, MCL, WM, or MZL from 6/2016-6/2022 (index period). Pts were required to be continuously enrolled for 60 days pre- and 365 days post-index date, defined as the date of first cancer diagnosis. Incidence and prevalence of MH conditions of interest (anxiety, depression, stress reaction/adjustment disorder, insomnia, post-traumatic stress disorder [PTSD]) were categorized based on if diagnoses were post- or pre-index date. All-cause healthcare resource utilization (HCRU) and costs were measured during the 1-yr follow-up period. Results: Approximately half of newly diagnosed 36,054 LG-NHL pts (CLL/SLL=48.0%; FL=52.7%; MCL=57.2%; WM=50.5%; MZL=52.5%) had either an incident (19.4-25.7%) or prevalent (28.6-32.1%) MH condition diagnosis following their cancer diagnosis (Table). There were no significant demographic differences in pts with and without MH conditions. LG-NHL pts suffered most from anxiety (30.9-38.2%) and depression (27.5-31.9%), followed by insomnia (16-23.1%), stress (10.3-13.5%), and PTSD (1.4-1.9%). Median time from cancer diagnosis to onset of a MH condition was 334 days for CLL/SLL, 301 for FL, 248 for MCL, 351 for WM, and 328 for MZL. LG-NHL pts with an identifiable MH diagnosis had significantly higher costs and HCRU compared to those without; for example, in CLL/SLL pts with MH diagnosis, outpatient visits were 1.4 times higher, inpatient admissions 3.0 times higher, and costs 2.1 times higher than those without (all P=0.0001). HCRU and cost increases were also observed in MCL, FL, WM, and MZL pts with MH diagnosis. Conclusions: This real-world study uncovered a high proportion of LG-NHL patients suffer from MH conditions, incurring higher financial burden than those without. With advancements in new treatments, there remains unmet need of MH burden in these pts. [Table: see text]

Introduction: Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are the most prevalent types of leukemia in the United States. Given the emergence of novel CLL/SLL therapies, it is important to understand real-world treatment characteristics and unmet needs. The objectives of this retrospective cohort study were to examine patient characteristics, treatment patterns, and associated outcomes for patients with CLL/SLL, overall, and by CLL and SLL, respectively. Methods: A retrospective study was conducted using Symphony Integrated Dataverse (IDV ®), a comprehensive, longitudinal, open-claims database, and integrated electronic medical record data. Patients aged ≥18 years with ≥1 diagnosis for CLL or SLL and who initiated a first-line or second-line treatment between January 1, 2020, and December 31, 2022 (index period) were included in the study. Index date was defined as the date of treatment initiation. Patients were required to be continuously enrolled for 365 days prior to the index date and ≥90 days following the index date. Patient data were included until patients were lost to follow-up or to the end of the study period (March 31, 2023). Treatment patterns were examined with the following treatment regimens and stratified by line of therapy: chemotherapy (including bendamustine-based and other chemotherapy), anti-CD20-based, Bruton tyrosine kinase inhibitors (BTKiibrutinib- and acalabrutinib-based), and venetoclax-based therapy. Zanubrutinib use was not captured in the BTKi treatment category as its CLL/SLL indication approval date (January 19, 2023) was outside the index period. Discontinuation rate was defined as the percentage of patients who discontinued their current treatment regimen within 90 days. Healthcare resource utilization was measured by number of outpatient visits, inpatient visits, and other medical/hospital services per patient per month (PPPM) during the treatment regimen. Results:There were 17,748 and 5,667 patients with CLL/SLL who initiated a first-line or second-line treatment regimen during the index period, respectively. The most frequently used treatment regimens in first line were BTKi (49.9%), followed by anti-CD20 (26.1%), venetoclax (15.4%), and chemotherapy (8.6%). BTKi continued to be the predominant treatment (49.6%) in second line, followed by venetoclax (30.9%), chemotherapy (10.4%), and anti-CD20 (9.2%). First-line patients treated with BTKi regimens were older and Medicare-insured when compared with patients receiving venetoclax-based regimens (65+ years: 77.1% vs 66.9%, P-value &lt;0.001; Medicare: 61.7% vs 53.0%, P-value &lt;0.001). Patients receiving BTKi had significantly lower discontinuation rates compared with other treatment regimens during both first and second lines of therapies (Figure 1). Mean PPPM outpatient visits, inpatient visits, and other medical/hospital services were less frequent with BTKi therapies vs other treatment regimens across both lines of therapy (Table 1). Of the 17,748 patients initiating first line of therapy, 13.3% had SLL while the remaining 86.7% had CLL. The proportion of patients with SLL vs CLL decreased in second line and second line or later (8.0% vs 92.0% and 6.8% vs 93.2%, respectively). Treatment discontinuation rate in SLL patients was higher than that in CLL patients in first line (32.41% and 25.08%, respectively); however, discontinuation rates became comparable with later lines of therapy. Across all lines of therapy, healthcare resource utilization was significantly higher in SLL patients than CLL patients. Median PPPM outpatient visits were 1.02 for SLL and 0.67 for CLL. Median PPPM for other medical/hospital services was 0.7 for SLL and 0.23 for CLL. Conclusions: BTKi therapy, the primary treatment regimen across first- and second-line therapies, has significantly lower discontinuation rate and healthcare resource utilization compared with other treatment regimens. Further studies are needed to evaluate real-world clinical outcomes of CLL/SLL regimens to support evidence-based treatment decisions.