1L Chronic Lymphocytic Leukemia Research Articles

Assessing Adoption of Standard of Care and Comparing Clinical and Demographic Differences in First-Line (1L) Treatment (Tx) of Chronic Lymphocytic Leukemia (CLL)

Assessing Adoption of Standard of Care and Comparing Clinical and Demographic Differences in First-Line (1L) Treatment (Tx) of Chronic Lymphocytic Leukemia (CLL)

Real-World Comparison of Healthcare Costs of Venetoclax-Obinutuzumab Vs. Btki Use Among Elderly U.S. Medicare Beneficiaries with Chronic Lymphocytic Leukemia in the Front-Line (1L) Setting

Background: Since the March 2016 FDA approval of ibrutinib as a front-line therapy in chronic lymphocytic leukemia (CLL), BTK inhibitors (BTKi) used as continuous therapy until progression or toxicity, are increasingly utilized early in the CLL treatment pathway. Conversely, the BCL-2 inhibitor venetoclax, approved for front-line (1L) CLL in May 2019, has been shown to generate durable responses. As a result, venetoclax has gained approval with a fixed treatment duration wherein a venetoclax plus obinutuzumab (VenO) regimen is to be completed after 12 months in the 1L setting. Fixed-duration therapy with a treatment-free remission has the potential advantage of lowering health care costs by avoiding continuous exposure to treatment. However, little real-world evidence has been generated to assess the potential economic benefits of a fixed-duration treatment such as VenO relative to treat-to-progression therapies like BTKis. The objective of this study was to examine healthcare costs before and after completion of the fixed-duration treatment period for VenO relative to that observed for BTKis in a national sample of elderly U.S. Medicare beneficiaries with CLL in the 1L setting. Methods: Our analysis used 2016-2021 100% Medicare Parts A, B, and D claims. Elderly fee-for-service Medicare beneficiaries initiating VenO (VenO group) or an available BTKi treatment (BTKi group) between 6/1/2019 and 6/30/2020 (index date = first prescription fill date) were included in the sample. Additional inclusion criteria for both groups were as follows: (a) ≥66 years old, (b) ≥1 diagnoses of CLL and no diagnoses for other indications of the index agent in the 12-month pre- and post-index period, (c) continuous medical and prescription coverage in the 36 months pre- and 12 months post-index period, (d) no prior CLL treatment in the 36-month pre-index period (i.e., to proxy 1L patients), and (e) continuous medical and prescription coverage from 13 to 18 months after the index date or until death if it occurs earlier (to capture costs after fixed-duration VenO treatment is completed). Healthcare cost measures included all-cause and CLL-related monthly total, prescription, and medical costs. Mean monthly cost measures were captured for both groups over two fixed time periods calculated from the index date: Month 0 to 12 (i.e. proxy for on-treatment period for VenO) and Month 13 to Month 18 (i.e. proxy for off-treatment period for VenO). Risk-adjusted monthly costs were estimated using generalized linear models controlling for differences in sociodemographic and clinical factors between the two groups. Difference-in-Difference method was used to assess reduction in costs across the two fixed time periods. Results: The final sample contained 193 patients (pts) in the VenO group (mean [SD] age 75.6 [5.5] years, 69.4% male, 90.2% White) and 1,577 pts in the BTKi group (mean [SD] age 77.6 [6.3] years, 55.8% male, 92.5% White). Between months 0 to 12, risk-adjusted all-cause monthly total costs were slightly lower for VenO pts ($13,887) than BTKi pts ($14,492) (Table 1). However, during months 13 to 18 the monthly all-cause total costs declined by 67% for VenO pts ($13,887 to $4,462) but only by 10% for BTKi pts ($14,492 to $13,051). Hence, the relative reduction in costs across the two periods was significantly larger for VenO (-$9,425) vs. BTKI (-$1,441) pts (i.e. Difference-in-Difference=-$7,984, p<0.001). Similar patterns were observed for CLL-related costs with the substantially larger reductions in CLL-related total monthly costs (-$9,880 VenO vs. -$1,753 BTKi, p<0.001) for the VenO group relative to BTKi group being primarily driven by the larger reduction in CLL-related monthly prescription costs (-$9,437 VenO vs. -$2,020 BTKi, p<0.001) (Table 1). Conclusions: This real-world study of elderly Medicare beneficiaries with CLL found a large reduction in monthly health care costs in the VenO group after the fixed-duration treatment period of 12 months. This drop was largely driven by the reduction in CLL-related prescription drug costs; however, similar declines were not observed in the BTKi group. Hence, the costs for pts on VenO after the fixed-duration treatment period were approximately $8000 per month lower than the BTKi group. Our study highlights the substantial economic benefits of VenO relative to treat-to-progression therapies like BTKis and carries implications for treatment decision-making CLL.

Understanding Patient and Physician Perceptions Regarding Treatment-Related Adverse Events in First-Line Chronic Lymphocytic Leukemia (CLL)

Background Chronic Lymphocytic Leukemia (CLL) patients have various treatment options which are all associated with different adverse events. A limited number of studies have explored how patients and physicians perceive these adverse events in the frontline treatment setting. Understanding the similarities and differences in perceptions between physicians and CLL patients is an important factor in supporting shared decision-making. Aims The objective of this multi-country study was to understand the differences in patients' and physicians' perception on treatment-related adverse events in CLL. Methods CLL patients and physicians managing CLL (oncologists, hematologist-oncologists, and hematologists) were invited to complete an online survey. Participants were recruited from the US, UK, Germany, France, and Australia. The survey included a best-worst scaling (BWS) exercise to assess how ‘bothersome’ 14 potential adverse events associated with 1L CLL treatments were perceived. In a series of 18 BWS choice tasks, participants chose which was most ‘bothersome’ and which was ‘least bothersome’ among subsets of 4 adverse events. A hierarchical Bayesian (HB) model was used to estimate BWS scores for each treatment-related adverse event: BWS scores sum to 100 for each participant and a higher score indicates that an adverse event is relatively more ‘bothersome’. Results The study included 192 patients and 259 physicians. The top four most bothersome adverse events were the same for both patients and physicians, however, these were ranked in a different order (Table 1). Physicians ranked the ‘risk of cardiac events/atrial fibrillation/flutter that may require medical treatment and/or hospitalization’ and ‘risk of bleeding (hemorrhage) that requires medical intervention and/or hospitalization’ as their 2 most bothersome adverse events while patients ranked ‘Risk of infection, such as pneumonia or blood infections (sepsis) requiring medical intervention and/or hospitalization’ and ‘Risk of tumor lysis syndrome (TLS) which requires hospitalization’ as their 2 most bothersome adverse events (Table 1). The 2 least bothersome adverse events for both physicians and patients were ‘Risk of mild-to-moderate muscle, joint or bone pain (mild-to-moderate pain not interfering with daily activities) that might go away with medication’ and ‘Risk of mild-to-moderate headache (not limiting daily activities or limiting only instrumental activities such as cooking, cleaning, transportation, laundry, etc.) that might go away with medication’ (Table 1). Among patients who had experienced an adverse event (N=111), 62 (56%) reported that it had impacted their quality of life. These patients rated the following adverse events as more bothersome compared to those who had not experienced adverse events impacting quality of life: ‘risk of infection, such as pneumonia or blood infections requiring medical intervention and/or hospitalization’ (BWS scores=13.88 vs. 11.79) and ‘a side effect resulting in stopping the medication’ (9.46 vs. 6.00). These patients also rated the following adverse events as least bothersome: ‘risk of severe headache that might lead to hospitalization’ (9.55 vs. 11.68), ‘risk of severe vomiting that might lead to hospitalization’ (8.97 vs. 10.70), and ‘risk of severe muscle joint or bone pain’ (7.32 vs. 10.59), compared to those not experiencing adverse events impacting quality of life. Conclusions Patients' and physicians' perceptions were generally aligned on what adverse events related to 1L CLL treatments are most and least bothersome. However, the rank-ordering of the most bothersome adverse events varied between patients and physicians: patients were more concerned about a risk of infection or tumor lysis syndrome whereas physicians thought that a risk of cardiac event and the risk of bleeding were the most bothersome adverse events. Patients expressed hardly any concern about a risk of mild-to-moderate headache that could be resolved with medication. Interestingly, patients who had experienced a prior adverse event had differing results to patients who had not. These results should further inform and facilitate conversations between physicians and patients and improve shared decision-making when selecting a 1L regimen to treat CLL.

Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-Line Treatment with Ibrutinib Versus Acalabrutinib

Introduction: Treatment guidelines recommend Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib (once-daily) and acalabrutinib (twice-daily) as preferred regimens for chronic lymphocytic leukemia (CLL); however, there are no studies comparing the effectiveness of ibrutinib and acalabrutinib as first-line (1L) therapy in CLL. This study investigated time to next treatment (TTNT) for patients with CLL initiated on 1L ibrutinib or acalabrutinib in real-world (RW) clinical practice in the US. Methods: Specialty pharmacy electronic medical records from academic integrated care networks (11/21/2018-4/30/2022) were used to identify adults with CLL who initiated ibrutinib or acalabrutinib in 1L (index date) on or after the date of acalabrutinib approval for CLL (11/21/2019). A washout period of ≥12 months without antineoplastic agent use pre-index was required to confirm use as 1L therapy. Patients were excluded if there was concomitant use of another antineoplastic agent during the first 28 days post-index. Characteristics evaluated in the 12-month baseline period were compared between ibrutinib and acalabrutinib cohorts using t-tests for continuous variables and chi-square tests for categorical variables. TTNT was defined as the time from the index date to the initiation a next or additional treatment. Patients without a next/additional treatment were censored at death or end of data (4/30/2022). Patients with a within-class BTKi switch at any time post-index were censored at time of switch, as this may have indicated a switch due to tolerability rather than progression. Patients who added an anti-CD20 antibody or venetoclax to the BTKi within 180 days post-index were censored at time of add-on, as these may not have indicated overt disease progression but rather late initiation of a second anti-cancer agent as a 1L combination treatment strategy. Beyond 180 days, anti-CD20 or venetoclax add-ons were considered as a next/additional treatment. TTNT was described using Kaplan Meier curves and compared between ibrutinib and acalabrutinib using a Cox proportional hazards model adjusted for the following baseline variables: age, gender, region, race, year of index date, Quan-Charlson Comorbidity Index (Quan-CCI), chronic pulmonary disease (CPD), peripheral vascular disease, hypertension, atrial fibrillation (AF), metastatic cancer, use of corticosteroids, and use of antiplatelets. Results: Among 710 and 373 patients in the ibrutinib and acalabrutinib cohorts, respectively, mean age was 71.5 and 72.4 years (P=0.159) and 38.5% and 38.3% were female (P=0.971; Table). Mean baseline Quan-CCI score was similar for ibrutinib and acalabrutinib (3.1 vs 3.0; P=0.597); a higher proportion of patients in the ibrutinib cohort had CPD (13.6% vs 8.8%; P=0.024), peripheral vascular disease (7.8% vs 4.1%; P=0.022), and hypertension (41.4% vs 32.2%; P=0.003) at baseline, while AF was similar (7.0% vs 9.9%, P=0.098). Baseline corticosteroid use was lower in the ibrutinib cohort (14.5% vs 20.1%; P=0.018), but antiplatelet use was higher (7.0% vs 3.5%; P=0.017). Mean (median [range]) follow-up was 17.1 (18.1 [1.0-29.3]) months for the ibrutinib cohort and 12.5 (11.9 [1.0-29.1]) months for the acalabrutinib cohort. Four/710 (0.6%) patients in the ibrutinib cohort and 16/373 (4.3%) in the acalabrutinib cohort added an anti-CD20 antibody to the BTKi within 180 days and were censored at that point. Ten/710 (1.4%) and 8/373 (2.1%) patients added venetoclax to ibrutinib or acalabrutinib within 180 days and were censored at that point. The proportion of patients in the ibrutinib cohort who initiated a next or additional treatment was 5.9% relative to 7.5% for acalabrutinib. After adjusting for baseline characteristics, patients treated with acalabrutinib were 89% more likely to start a next or additional treatment than those treated with ibrutinib (hazard ratio = 1.89 [95% confidence interval] = [1.12, 3.13]; P=0.016; Figure). Results were similar when censoring anti-CD20 add-ons at any time (hazard ratio = 1.82 [95% confidence interval] = [1.08, 3.03]; P=0.025). Conclusions: In this large US RW study, patients with CLL treated with 1L acalabrutinib were significantly more likely to start a next treatment or add/intensify therapy than those treated with 1L ibrutinib. RW treatment patterns also suggest a higher propensity to add an anti-CD20 antibody to acalabrutinib versus ibrutinib in 1L CLL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Shift in First-Line Therapies for United States Veterans Health Administration (VHA) Patients with Chronic Lymphocytic Leukemia (CLL) from 2014 to 2021

Introduction: The emergence of novel agents (NAs) in chronic lymphocytic leukemia (CLL) management marks a move away from a chemotherapy-based paradigm in less than a decade. This has resulted in better treatment tolerance and improved overall survival. The Veteran Health Administration (VHA) offers an attractive population for examining CLL treatments patterns because of two main reasons. It serves mainly older white male population, where incidence of CLL is higher, and is the only single payer national health program that provides equal access to medications. This aim of the study is to assess large population-based uptake of the NAs and to analyze the trends in chemotherapy-based regimen replacement by NA in front-line (1L) CLL. Methods: This is a retrospective study of structured EMR data for adult patients with ICD9 and ICD10 CLL codes within the VHA who initiated 1L treatment with one of 14 CLL treatment [eight NAs and six chemotherapy-based regimens] from 1/1/2014 to 12/31/2021. Data were extracted from the VHA electronic health record. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Descriptive statistics were used to summarize baseline characteristics and treatments by calendar year. Results: A cohort of 4,473 patients were identified who received at least one 1L CLL therapy of interest. The median age was 69 years and 98% were male. The proportion of patients who received an NA as 1L treatment for CLL increased from 2014 to 2021, with a corresponding decrease in chemotherapy-based regimens (Figure 1). In 2017, the proportion of NAs surpassed chemotherapy-based regimen use (52 vs 48%, respectively). This gap continued to widen throughout the study period, with the use of chemotherapy-based regimens plateauing for the last three fiscal years of the study period at ~20%. The use of ibrutinib (90%) accounted for the greatest proportion of 1L NA use over the study period, followed by venetoclax (5%), acalabrutinib (4%), and idelalisib (1%). Until 2018, ibrutinib made up nearly 100% of the NA use with a steady decline thereafter reaching 62% in 2021. The proportion of patients on 1L venetoclax increased annually from 2018 (2%) to 2021 (19%). Similarly, the proportion of patients on 1L acalabrutinib increased annually from 2019 (0%) to 2021 (19%). The proportion of patients on 1L idelalisib increased early in 2015 (4%) but declined throughout the remaining study period (0-1%) (Figure 2). Conclusions: This is one of the largest studies that provides important epidemiological data regarding emerging 1L treatment patterns among VHA patients with CLL. There has been a major shift in 1L treatments with NAs outpacing chemotherapy-based regimens from 2017-2021. Within NAs, there is an ongoing transition from first generation Bruton Tyrosine Kinase (BTK) inhibitor to fixed duration treatments and second generations BTK inhibitors with better side effect profiles. The trend shift will continue to evolve as multiple NAs combinations that offer deeper response and limited/guided treatment duration enter the treatment landscape. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Systematic Review and Network Meta-Analysis of Frontline Targeted Therapy in Chronic Lymphocytic Leukemia Shows Comparable Efficacy but Distinct Toxicity

Introduction: Targeted therapies inhibiting Bruton Tyrosine Kinase (BTK) (ibrutinib, acalabrutinib, and zanubrutinib) and Bcl-2 (venetoclax) have improved survival when given first line (1L) to patients with chronic lymphocytic leukemia (CLL). However, no head-to-head trials of 1L targeted therapies exist to guide clinicians on selection of optimal therapy for their patients. We performed a systematic review and network meta-analysis (NMA) to understand the relative efficacy and toxicity of 1L CLL regimens, including newer regimens of ibrutinib/venetoclax (IV) and zanubrutinib not previously assessed in NMA. Methods: We performed a systematic literature search from 2009-2022 for randomized trials of treatment-naïve adults with CLL who were deemed unfit due to age or comorbidities. Endpoints were progression free survival (PFS) at 24 and 48 months, overall response rate (ORR), percentage of patients with grade 3 or higher adverse event (AE), discontinuation due to AE, and rates of AEs of clinical interest. We used a Bayesian hierarchical random-effects models for mixed multiple treatment comparisons to estimate the relative treatment effect of each intervention compared with a common comparator. Results: Our search yielded 12 clinical trials including 15 unique 1L regimens (Fig 1). PFS and ORR of common comparators were consistent across trials except 24-month PFS for chlorambucil/obinutuzumab (CO) which ranged from 31%-64% likely due to variable duration of chlorambucil and variable inclusion of patients with del(17p). Compared to CO, only acalabrutinib/obinutuzumab (AO) showed statistically significant improvement in 24-month PFS with hazard ratio (HR) 0.13 and 95% confidence interval (CI) 0.017-0.97 (Fig 1). In general, targeted therapies trended towards longer PFS compared to chemotherapy-based regimens, though there is insufficient power to demonstrate statistical significance. We found no statistically significant differences in 24-month PFS, 48-month PFS, or ORR between targeted therapies. Regarding toxicity, no statistically significant differences in proportion of patients experiencing grade 3 or higher AE were found across regimens, though single agent acalabrutinib and zanubrutinib trended toward less toxicity than CO with risk ratio (RR) 0.71, 95% CI 0.45-1.1 and RR 0.66, 95% CI 0.30-1.5, respectively. No statistically significant differences in discontinuation rates were found, though IV trended towards higher discontinuation rate than CO (RR 6.1, 95% CI 0.71-74). There were no statistically significant differences in rates of atrial fibrillation, infection, anemia, or neutropenia. However, grade 3 or higher thrombocytopenia was significantly lower with zanubrutinib than CO (RR 0.069, 95% CI 0.0048-0.92). Conclusions: Using NMA, we demonstrate that PFS is improved from the pre-targeted therapy standard of care by AO, but, amongst targeted therapies, no significant differences in efficacy were identified. Our results differ from previously published NMAs which have shown superior PFS with AO compared to other targeted therapies, likely due to inclusion of additional trials of common comparators (Foa et al, CLL5) as well as newer trials assessing IV and zanubrutinib (GLOW, SEQUOIA cohort 1) in this analysis. All four trials add heterogeneity to common comparator outcomes, resulting in widened confidence intervals and loss of statistical significance. This is the first assessment, to our knowledge, of relative rates of specific AEs, and we found that zanubrutinib showed lower rates of thrombocytopenia than pre-targeted therapy standard of care. Establishing the absence of significant difference in efficacy of frontline targeted therapies in CLL allows the clinician and patient to select therapy based on other factors, namely planned duration, toxicity profile, medication interactions, and cost. Figure 1. 24-month PFS Network and Forest Plot 1Chl = Chlorambucil; Acal = Acalabrutinib; Acal/Obin = Acalabrutinib/Obinutuzumab; BR = Bendamustine/Rituximab; Chl/Ofa = Chlorambucil/Ofatumumab; Chl/Ritux = Chlorambucil/Rituximab; Chl/Ritux + Mtn = Chlorambucil/Rituximab + maintenance Rituximab; Flu = Fludarabine; Ibr = Ibrutinib; Ibr/Obin = Ibrutinib/Obinutuzumab; Ibr/Ritux = Ibrutinib/Rituximab; Ibr/Ven = Ibrutinib/Venetoclax; Ven/Obin = Venetoclax/Obinutuzumab; Zan = Zanubrutinib Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

EE12 A Probabilistic Cost-Effectiveness Analysis of Venetoclax and Obinutuzumab As a First-Line, 12-Month, Fixed Duration Therapy in Chronic Lymphocytic Leukemia (CLL) in Canada

To assess the cost effectiveness of venetoclax + obinutuzumab (VENCLAXTA® + GAZYVA®), (Ven+O) for the frontline treatment of CLL (1L CLL) in Canada from a publicly funded healthcare system perspective.

P661: POPULATION-WIDE PATTERNS OF CARE IN CHRONIC LYMPHOCYTIC LEUKEMIA IN AUSTRALIA: AN ANALYSIS OF THE PHARMACEUTICAL BENEFITS SCHEME DATASET

Background: The treatment landscape in patients with chronic lymphocytic leukemia (CLL) is changing with the approvals of Bruton’s tyrosine kinase inhibitors (BTKis) in Australia. Aims: We sought to understand the practice impact of the introduction of publicly funded novel agents for the treatment of CLL. The objective of this study was to describe the evolving treatment patterns of Australian patients with CLL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for CLL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset. This dataset includes the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for the treatment of CLL. First-line (1L) therapy was defined as the first treatments prescribed for CLL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess changes in treatment patterns. Results: Overall, 803 patients with CLL were identified. The majority of patients were male (65%) and age > 60 years (77%), with most being aged 70-79 years (33% of total). Many patients were receiving comedications at baseline, including antihypertensives (47%), antipsychotics or antidepressants (17%), and/or anticoagulants (13%). In the overall population (2011-2021), the majority of patients had received 1L treatment with fludarabine-cyclophosphamide-rituximab (FCR, 49%), chlorambucil ± CD20 (27%), or CD20 monotherapy (17%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included CD20 monotherapy (56%), BTKi (41%) or FCR (33%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 use of FCR in 1L decreased from 78% to 10%; and use of BTKis in R/R increased from 0% to 62%. Summary/Conclusion: CLL treatment patterns have significantly changed in Australia since the introduction of the BTKis (e.g., ibrutinib, acalabrutinib). The use of FCR in 1L CLL has decreased and use of BTKis in R/R patients has increased.

Population-wide patterns of care in chronic lymphocytic leukemia in Australia: An analysis of the pharmaceutical benefits scheme dataset.

e19518 Background: The treatment landscape in patients with chronic lymphocytic leukemia (CLL) is changing with the approvals of Bruton’s tyrosine kinase inhibitors (BTKis) in Australia. We sought to understand the practice impact of the introduction of publicly funded novel agents for the treatment of CLL. The objective of this study was to describe the evolving treatment patterns of Australian patients with CLL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for CLL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset. This dataset includes the dispensing records for 10% of the Australian population and captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for the treatment of CLL. First-line (1L) therapy was defined as the first treatments prescribed for CLL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess changes in treatment patterns. Results: Overall, 803 patients with CLL were identified. The majority of patients were male (65%) and age > 60 years (77%), with most being aged 70-79 years (33% of total). Many patients were receiving comedications at baseline, including antihypertensives (47%), antipsychotics or antidepressants (17%), and/or anticoagulants (13%). In the overall population (2011-2021), the majority of patients had received 1L treatment with fludarabine-cyclophosphamide-rituximab (FCR, 49%), chlorambucil ± CD20 (27%), or CD20 monotherapy (17%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included CD20 monotherapy (56%), BTKi (41%) or FCR (33%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 use of FCR in 1L decreased from 78% to 10%; and use of BTKis in R/R increased from 0% to 62%. Conclusions: CLL treatment patterns have significantly changed in Australia since the introduction of the BTKis (e.g., ibrutinib, acalabrutinib). The use of FCR in 1L CLL has decreased and use of BTKis in R/R patients has increased.

Real-world clinical outcomes in patients receiving either ibrutinib or chemo-immunotherapy (CIT) as first-line (1L) treatment for chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL): A retrospective analysis.

e19057 Background: Ibrutinib is an oral, once daily Bruton’s tyrosine kinase inhibitor and is the only targeted treatment that has demonstrated progression-free survival and overall survival in multiple phase 3 trials across age, fitness, and high-risk markers for CLL/SLL. This study examined the trends in genomic testing and compared outcomes of first line (1L) CLL patients treated with ibrutinib or CIT in clinical practice. Methods: The nationwide Flatiron Electronic Health Record-derived de-identified database (03/04/2016-08/31/2021) was used to select patients with CLL/SLL who had ≥2 clinic visits and started 1L therapy with ibrutinib or CIT. Patient baseline characteristics prior to 1L initiation were compared between the two treatment groups. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between treatment groups. Kaplan-Meier (KM) analysis was used to evaluate time to next treatment (TTNT) from 1L initiation. Two subgroup analyses were performed among patients with high-risk cytogenetic markers (deletion 17p, 11q or unmutated IGHV) and those without IGHV testing. Results: Overall, the rate of testing for high-risk markers remain suboptimal, while cytogenetic testing for del17p or del11q improved from 52.3% to 74.3%, coinciding with approval of ibrutinib for del17p in 2014, IGHV testing remains infrequent and low at 37.7%. 1882 patients (61.4%) received 1L ibrutinib monotherapy (mean age 71, median follow-up 26 months), and 1182 (38.6%) received a CIT regimen (mean age 68, median follow-up 33 months). More patients treated with ibrutinib had a known high-risk cytogenetic marker (44% vs. 34%), especially in those with deletion 17p (15% vs. 4%), than those treated with CIT. Ibrutinib-treated patients significantly decreased risk of initiating a subsequent treatment by 51% (Table), the high-risk group by 60%, and those with unknown IGHV status by 49%. Conclusions: Consistent with clinical trial evidence, treatment with ibrutinib among 1L CLL patients resulted in a statistically significantly lower risk of initiating subsequent treatment than those treated with CIT, both overall and in the subgroups of patients with high-risk cytogenetic markers and patients without IGHV testing. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical outcomes, especially in the novel agent era. Recent IGHV testing in community practice to assess genetic risk in CLL remains suboptimal.[Table: see text]

Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US)

Background: There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration. Here, we assessed the evolution of molecular testing patterns, treatment patterns, and clinical outcomes over time in patients receiving 1L CLL treatment in a real-world US database.Methods: This was a retrospective cohort study using the Flatiron Health database, a longitudinal database comprising de-identified, patient-level, structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. Patients aged 18 years and older who were diagnosed with CLL and initiated 1L treatment between December 2015 and December 2020 were selected. Participants who took part in a clinical trial in any line of therapy, or who had any other primary cancer diagnosis, were excluded. Baseline characteristics, including testing patterns, at initiation of 1L treatment were assessed using descriptive statistics. Treatment patterns and outcomes, such as time to next treatment or death (TTNTD), were analyzed. Kaplan-Meier analysis was used to estimate TTNTD.Results: Among 3654 patients with treatment-naive CLL who were selected from the de-identified database, the mean age at 1L treatment initiation was 70 years (range, 29-85); 64.3% of patients were male; 72.1% were White, 8.2% Black, 3.9% Hispanic/Latino, 1.0% Asian, and 14.9% were of other ethnicity/race. Approximately one-third (34.7%) of patients had Rai stage 0-I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage.Testing patterns: The majority of identified patients (3202/3654; 87.6%) had undergone cytogenetic testing, fluorescence in situ hybridization, or IGHV mutation testing. Compared with 2015-2016, testing rates were higher in 2019-2020 for chromosome 17p deletion (del(17p); 36.1% vs 45.7%, respectively; p<0.001) and for IGHV mutation status (84.7% vs 89.2%, respectively; p=0.003). Overall, 11.0% of patients had del(17p). Of those tested for IGHV (1472/3654; 40.3%), 58.3% had unmutated IGHV.Treatment patterns: The 10 most commonly used 1L CLL treatments, which overall represented 91.8% of all 1L treatments, and their evolution over time, are reported in Table 1. Of the patients receiving these top 10 1L treatment regimens overall, 45.7% received regimens including novel targeted oral agents, 33.4% received chemo-immunotherapy (CIT), and 19.7% received anti-CD20 monotherapy. Evaluation of each 2-year period shows that treatment patterns for the top 10 1L treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015-2016) to 63.8% (2019-2020) (p<0.001), while use of CIT and chemotherapy decreased over time (Table 2). Approximately 30.0% (1088/3654) of 1L-treated patients went on to receive second-line treatments.Outcomes: Median TTNTD was 34.4 months for all patients receiving 1L CLL treatment, and 36.5 months for patients who received the 10 most common 1L treatments across the 6-year study period (n=3360). Median TTNTD was 47.0 months for patients who received novel targeted oral agents and 41.5 months for patients who received CIT (unadjusted p=0.16). When evaluating outcomes in patients with high-risk cytogenetics, median TTNTD was 29.1 months for patients with del(17p) and 37.2 months for those with unmutated IGHV, but was longer in those patients who received treatment with novel targeted oral agents (median TTNTD of 43.9 and 46.7 months, respectively; Table 3).Conclusions: This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups. Following on from this, a comparative study of TTNTD for novel oral agents versus CIT, and analyses of outcomes of different sequencing of therapies, will be conducted. [Display omitted] DisclosuresMato: Nurix: Research Funding; Johnson and Johnson: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; MSKCC: Current Employment; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ravelo: Genentech, Inc.: Current Employment; Roche Holdings: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. To: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Schuldt: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Biondo: Genentech, Inc.: Current Employment; Roche: Current holder of individual stocks in a privately-held company.

Healthcare Resource Utilization and Costs Associated with Obinutuzumab Plus Bendamustine Versus Rituximab Plus Bendamustine for First-Line Treatment of Follicular Lymphoma

Background: Obinutuzumab (G) is an anti-CD20 monoclonal antibody approved in the US for the first-line (1L) treatment of follicular lymphoma (FL), relapsed or refractory FL, and 1L chronic lymphocytic leukemia. G plus chemotherapy (G-chemo) demonstrated superior progression-free survival versus (vs) rituximab (R) plus chemotherapy (R-chemo) in patients with previously untreated FL in the Phase III, randomized GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017). R-bendamustine (R-benda) and G-bendamustine (G-benda) are among the most commonly used chemoimmunotherapy (CIT) regimens for FL (Ta et al. J Clin Oncol 2021), and information on comparative healthcare resource use (HRU) and real-world costs associated with G-chemo vs R-chemo in previously untreated FL patients is limited. The aim of this study was to compare HRU and costs for G-benda and R-benda for the 1L treatment of FL using US claims databases.Methods: This was a retrospective cohort study using administrative claims data from the IQVIA PharMetrics® Plus and IBM® MarketScan Commercial and Medicare Supplemental databases. We identified patients aged ≥18 years, who had ≥1 inpatient claim or ≥2 outpatient claims with a diagnosis of FL from February 1, 2015 to September 30, 2020, and received 1L R-benda or G-benda between February 1, 2016 and March 31, 2020. The first claim for FL treatment was the index date. All patients had ≥12 months of pre- and ≥6 months of post-index continuous enrollment in medical and pharmacy benefits. Patients with other primary cancers, FL treatment, diffuse large B-cell lymphoma (DLBCL), or stem cell transplant during the pre-index period, or clinical trial participation or end-stage renal disease during the study period were excluded. Patients initiating 1L G-benda were propensity score matched 1:2 with patients initiating 1L R-benda based on age, sex, Charlson Comorbidity Index (CCI), region, and insurance type. All-cause and FL-related (i.e. claim with a FL diagnosis in any position) HRU and costs (2020 USD) per patient per month (PPPM) during the follow-up period were reported. Patients were followed until the earliest of initiation of second-line therapy, end of continuous follow-up, or end of data availability.Results: Overall, 270 patients were included; of these, 90 (33.3%) patients receiving G-benda were matched to 180 (66.7%) patients receiving R-benda for 1L treatment of FL. 45.2% were male, and the mean (standard deviation [SD]) age and CCI at index date were 59.1 (9.9) years and 1.7 (1.1), respectively. Median follow-up was 7.4 months. After matching, baseline characteristics were well-balanced between R-benda and G-benda patients (standardized mean difference [SMD] <0.1). Both all-cause and FL-related HRU were similar between R-benda and G-benda treated patients across all service categories (Figure 1). Total all-cause mean [SD] PPPM costs were also similar in G-benda vs R-benda patients ($21,378 [$15,242] vs $21,352 [$14,145]; p=0.77) (Figure 2). The majority of the total costs were FL-related and comparable across both patient groups: $17,353 ($11,370) for G-benda vs $17,724 ($13,530) for R-benda (p=0.71). Specifically, FL-treatment related costs PPPM were $17,070 ($14,064) for G-benda; this is comparable to $16,138 ($11,828) PPPM for R-benda (p=0.39).Conclusions: Our study found similar total costs of care and HRU among patients receiving 1L G-benda versus those receiving R-benda, providing real-world economic evidence that complements clinical trial data supporting the use of G-chemo for 1L treatment of FL. [Display omitted] DisclosuresTo: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Ta: Genentech, Inc.: Current Employment. Seetasith: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Wang: The SPHERE Institute: Ended employment in the past 24 months; Aurinia Pharmaceuticals Inc.: Current equity holder in publicly-traded company; Novavax, Inc.: Current equity holder in publicly-traded company; Oragenics, Inc.: Current equity holder in publicly-traded company; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment; TG Therapeutics, Inc.: Current equity holder in publicly-traded company. Lai: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; AbbVie: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; Bristol-Myers Squibb: Current equity holder in publicly-traded company. Shapouri: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company.

Uptake of Novel Agents (NAs) As First-Line Treatments for Black and White Patients with Chronic Lymphocytic Leukemia (CLL) in the Veterans Health Administration (VHA): A Retrospective Cohort Study

IntroductionSince the introduction of NAs in 2013, the treatment paradigm for CLL has changed significantly with the increased uptake of NAs for first line (1L) and refractory CLL. NA have introduced a personalized approach to CLL treatment that considers patient baseline characteristics, individual risk factors and preferences. 1 Despite improvement in survival outcomes with CLL, Black patients with CLL have demonstrated inferior overall survival as compared to White patients. 2 Studies have shown a difference in disease biology between Black and White patients. 3 Differences in disease biology and access to medical care and treatment have contributed to racial disparities. The purpose of this study was to assess the uptake of NAs in the VHA where access to care is equal for both Black and White patients.Methods:A retrospective study was conducted which observed adult patients with an ICD code for CLL managed in the VHA from 2014 to 2017. Electronic and manual data was extracted to review start and stop dates for 1L CLL therapies. Data up to twenty years prior to the CLL treatment initiation date was reviewed to define the baseline variables. Descriptive statistics were used to summarize the data, and chi-square and Student's t-tests were used to compare NA use, baseline characteristics, healthcare resource use, and complications. A two-step nominal logistic regression model was used to determine the effect of race on receipt of NAs. Baseline patient characteristics were compared with bivariable statistical tests and variables with a p-value less than 0.10 were subsequently entered into the multivariable nominal logistic regression model. P-values less than 0.05 were considered statistically significantResults:The study included 565 patients; 86% were White and 14% were Black. Black patients were younger than White patients with a median age of age 66 and 69 respectively, p< 0.0001 (Table 1). Overall, Black patients were less likely to receive NAs than White patients (14% vs. 26%, p=0.0165) (Table 1). However this difference narrowed over the study period. (Figure 2) Traditional chemotherapy/chemoimmunotherapy (CT/CIT), was more common in Black patients. White and Black patients experienced similar treatment outcomes and health care utilization (Table 2). When all baseline variables listed in Table 1 were compared for Black and White ptients, the following variables had p-values less than 0.10 and were subsequently entered into a multivariant model: patient age (p<0.0001), male sex (p=0.0901), peptic ulcer disease (p=0.0981), deep vein thrombosis (p=0.0976), intestinal disorders (p=0.0252), priority group 7-8 (p=0.0561), use of antihypertensives (p=0.0302), and fiscal year. In the multivariant model, with NA use as the dependent variable, Black race as the independent variable, and divergent baseline characteristics as the covariates, the only variables that were independently predictive of NA use were Black race (p=0.0243, OR=0.47, 95%CI=0.24-0.94) and fiscal year (p=0.0019).Conclusions:In this retrospective cohort study, there was a statistically significant difference in the use of NAs between Black and White patients with CLL in the VHA for the study period. However, when NA use was examined by year, the disparity was largest in the early study years with reduced differences in NA utilization over time. Potential limitations of this study include the smaller number of patients, biologic factors that were not captured, and potential confounding factors such as physician experience with NA use. With the introduction of more NAs, the VHA should pay close attention to ensure all patients receive equal access to new therapies. We hope to implement interventions to ensure that patients of all races have equal access to NAs as soon as they are introduced.

Safety, Efficacy and MRD Negativity of a Combination of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331)

Safety, Efficacy and MRD Negativity of a Combination of Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia - Results from a Phase 1b Study (GP28331)

Clinical and economic burden among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) receiving first-line (1L) chemoimmunotherapy (CIT) by risk status: A chart-linked claims analysis.

e19505 Background: In patients with CLL/SLL, high risk genetic abnormalities are associated with inferior responses to CIT, and the economic burden of this remains uncertain. This study aimed to compare real world clinical and economic outcomes in high risk and perceived non-high risk patients initiating 1L CIT. Methods: This retrospective cohort study identified patients with CLL/SLL from the HealthCore Integrated Research Database representing a national managed care population with over 58 million members. Medical records were obtained for eligible patients who initiated 1L CIT between 1/1/2007 and 7/31/2019 and underwent prognostic testing to classify them as high risk (HR: del17p, TP53 mutation, del11q or unmutated IGHV) or as non-high risk by FISH only (NHR: non-del17p and non-del11q). The first CIT claim date was the index date. Patients were required to have ≥12 months of pre-index and ≥30 days of post-index eligibility. Study outcomes included testing rate, time to next treatment (NT) or death, time to treatment failure (TF; defined as time to change of therapy, non-chemotherapy intervention, hospice care or death), and total plan paid costs (medical + pharmacy) per patient per month (PPPM) in the 1L period. Cox proportional hazard models and generalized linear models were used to calculate adjusted hazard ratio or rate ratio. Results: Among the 1,808 patients with CLL/SLL, 612 were FISH or IGHV tested and the rate of testing increased from 2007 to 2019 (30% to 44%), especially after adding ibrutinib for 1L CLL with del17p in NCCN guidelines v4.2014. Risk status was available for 253 patients (HR: 119; NHR: 134), with 80% of patients initiating 1L BR/FCR-based therapy in both cohorts. Median follow up was 26.4 vs. 25.8 months (HR vs NHR). HR patients had 65% higher risk of NT/death (median time: 2.4 vs 3.7 years), and 65% higher risk of TF (median time: 3.0 vs 4.9 years) compared to NHR patients (Table). The total costs PPPM were also significantly higher for HR patients in the 1L period ($12,194 vs $9,055, p=0.027; Rate Ratio=1.33, p&lt;0.001). Conclusions: Initiating 1L CIT among HR patients with CLL/SLL was associated with increased risks of NT/death, TF, and higher costs compared to NHR patients identified by FISH only. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical and economic outcomes, especially in the novel agent era. Recent testing practices to assess genetic risk in CLL remains suboptimal.[Table: see text]

Oncologist and Patient Preferences for Novel Agents in First-Line Treatment for Chronic Lymphocytic Leukemia: Commonalities and Disconnects.

PurposeTreatment for chronic lymphocytic leukemia (CLL) has changed dramatically with the approval of novel agents. Information regarding how patients and oncologists make trade-offs across attributes of novel therapies is limited. The purpose of this study was to understand how variations in attributes impact treatment choice among patients and oncologists.Patients and MethodsIn this study, 371 participants (patients [n=220] and oncologists [n=151]) completed an online discrete choice experiment (DCE) to quantify preferences for first-line (1L) CLL treatment with novel agents; participants chose between hypothetical treatment profiles consisting of eight attributes with varying levels taken from published literature. Hierarchical Bayesian models were used to estimate attribute level preference weights. The weights were used to compute relative importance, a measure of how influential an attribute is to treatment choice.ResultsIncreasing 2-year progression-free survival (PFS) from 75% to 95% had the greatest impact on preferences in 1L CLL treatment, accounting for 40% and 30% of the variation in preferences among patients and oncologists, respectively. Risk differences in atrial fibrillation (AF), infection, and discontinuation due to adverse events (AEs) were also important to patients and oncologists. Among both groups, risk differences in tumor lysis syndrome (TLS) and bleeding were least influential in treatment choice. Oncologists required 2–4 times higher increases in 2-year PFS than patients to accept increased risks of AF, discontinuation due to AEs, bleeding, TLS, and arthralgia/myalgia.ConclusionPatient–oncologist communication may be improved by a more focused discussion on the risks of AEs, relative to treatment outcomes, with patient goals in mind.

Cost-Effectiveness of a 12-Month Fixed Duration of Venetoclax in Combination with Obinutuzumab Versus Chemoimmunotherapy and Other Novel Combinations in First-Line Chronic Lymphocytic Leukemia in Canada

OBJECTIVES: To estimate the cost-effectiveness of venetoclax + obinutuzumab (GAZYVA®, G), (VEN+G) in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL) from a Canadian health care system cost perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival (PFS) and overall survival (OS) over a 10-year time horizon. Cost-effectiveness was estimated comparing 12-month fixed duration of VEN+G versus (vs) G + Chlorambucil (GClb) based on the CLL14 clinical trial (NCT02242942). Other comparators included Bendamustine + rituximab (BR), Chlorambucil + rituximab (Clb+R), Ibrutinib (Ibr), Acalabrutinib (Acala) and Acalabrutinib + GAZYVA (Acala+G). VEN+G was also compared to the combination of fludarabine, cyclophosphamide and rituximab (FCR) in the overall 1L CLL population which included unfit and fit patients. Relative efficacy of VEN+G vs other comparators was estimated using a network meta-analysis. Health state utilities and adverse event disutilities were derived from a systematic literature review and other published sources. Costs included CLL treatment, routine care and monitoring, adverse events, disease progression costs, subsequent treatment costs, and end of life care. Uncertainty was assessed using an underlying probabilistic model (probabilistic analysis of uncertainty generated from 5,000 iterations), through deterministic sensitivity analyses (i.e., one-way sensitivity analyses (OWSA)), and through a series of alternative scenario analyses. RESULTS: For the overall unfit 1L CLL patient population, the probabilistic total discounted costs incurred over a 10-year time horizon were as follows: $217,727 for VEN+G vs $312,287 for GClb, $399,219 for BR, $380,713 for Clb+R, $736,017 for Ibr, $868,797 for Acala and $916,139 for Acala+G. The probabilistic total discounted quality adjusted life years (QALYs) were 4.964 for VEN+G vs 4.750, 4.550, 4.422, 4.709, 5.269, and 5.359, respectively for the comparators. For the overall 1L CLL patient population, the probabilistic total discounted costs were $219,651 for VEN+G vs $312,570 for GClb, $342,195 for FCR, $397,262 for BR, $380,551 for Clb+R, $757,129 for Ibr, $868,388 for Acala, and $916,798 for Acala+G. The probabilistic total discounted QALYs were 5.888 for VEN+G vs 5.519, 5.067, 5.198, 5.073, 5.597, 6.259 and 6.380, respectively for the comparators. VEN+G was found to be less costly and more efficacious (i.e., dominant) compared to GClb, BR, Clb+R, Ibr and FCR. As a result, incremental cost utility ratios (ICERs) were not calculated for these comparators. Acala and Acala+G resulted in ICERs ranging from $1.4-$2.1 million per QALY gained relative to VEN+G, which is not cost-effective. Based on the probabilistic model and 5,000 simulations, VEN+G was found to be at least 97% cost-effective across all decision maker willingness-to-pay thresholds. The results from the deterministic model were found to be similar to the probabilistic model. Using the deterministic model, and in comparison to the most commonly prescribed treatment for 1L CLL in Canada (i.e., Ibr), the OWSA comparing VEN+G to Ibr found that the most influential variables in the model were the PFS and OS hazard ratios for Ibr and the utility values for PFS and post-progression survival. CONCLUSION: VEN+G is an effective novel fixed duration treatment option which leads to deep and durable responses for the treatment of patients with unfit 1L CLL and provides excellent value-for-money compared with existing chemoimmunotherapy and treat to progression novel combinations. Disclosures Chatterjee: Pharmerit: Current Employment. Van de Wetering:Pharmerit: Current Employment. Goeree:AbbVie Inc.: Consultancy. Desbois:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzi:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:AbbVie: Current equity holder in publicly-traded company. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company.

Patient and physician decision-making on the use of novel agents in chronic lymphocytic leukemia (CLL): What drives preferences?

148 Background: CLL treatment has changed dramatically with the approval of novel agents, but data to guide treatment decisions are still lacking. How patients (PTs) and oncologists (ONCs) prioritize treatment attributes is unknown. Methods: ONCs and PTs completed an online survey to quantify preferences for first-line (1L) CLL treatment with novel agents via a discrete choice experiment; ONCs and PTs chose between hypothetical treatment profiles with varying attribute levels taken from product labels, registrational trials, and real-world studies. Hierarchical Bayes models were used to estimate attribute level preference weights, which were used to compute relative importance (RI), a measure of how influential an attribute is in treatment choice out of a total of 100%. Results: For ONCs (N=151), 72% were in community practice. PTs (N=220) had a median age of 56 years; 32% were in active surveillance, 36% were in/had completed 1L treatment, and 32% were relapsed/refractory. Increasing 2-year progression-free survival (PFS) from 75% to 95% had the greatest impact on preferences, with a mean RI of 40% for PTs and 30% for ONCs (Table). When assessing trade-offs between 2-year PFS and other attributes, ONCs required the largest increase in PFS (11%) to compensate for an increased risk of atrial fibrillation (AF) from 5% to 20%. PTs required the largest increase in PFS (6%) to compensate for an increased risk of infection from 7% to 20%. ONCs (vs PTs) required 2–4-times higher increases in PFS to accept an increased risk of AF, discontinuation due to adverse events (AEs), bleeding, tumor lysis syndrome (TLS), and arthralgia/myalgia. Conclusions: ONCs and PTs valued PFS most when selecting a novel CLL agent. While both groups accepted potential risks in exchange for increased PFS, ONCs were less likely to accept a higher risk of AEs. ONCs and PTs may perceive the risks and benefits of novel agents differently. ONC–PT communication may be improved by a more focused discussion on the risks of AEs, relative to treatment outcomes, with patient goals in mind. [Table: see text]

Cost-Effectiveness of a 12-Month Fixed Duration of Venetoclax in Combination with Obinutuzumab in First-Line Chronic Lymphocytic Leukemia in the United States

INTRODUCTION: Historically chemoimmunotherapy has been the standard of care in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL). More recently several effective oral targeted agents, such as ibrutinib-based regimens, have provided effective chemotherapy-free treatment options in CLL. However, these therapies require continuous treatment until disease progression. Recently FDA approved (May 2019), venetoclax plus obinutuzumab (VenG) is a highly effective chemotherapy-free therapy that is used over a 12-month fixed treatment duration (Fischer et al, N Eng J Med 2019). The objective of this study is to estimate the cost-effectiveness of VenG in the treatment of 1L CLL from a US-payer perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival and overall survival over a lifetime horizon (20 years). Cost-effectiveness was estimated by comparing a 12-month fixed duration of VenG versus (vs.) chlorambucil-obinutuzumab (ClbG) based on the CLL14 clinical trial (NCT02242942). Other comparators included treat-to-progression therapies, such as ibrutinib (IBR), IBR + rituximab (IR), and IBR + G (IG), and a 6-month course of bendamustine + rituximab (BR). Using a network meta-analysis, the relative efficacy of VenG and ClbG vs. other selected comparators was estimated. Health state utilities and adverse event (AE) disutilities were derived from a systematic literature review and published health-technology assessment reports. To generate total quality-adjusted life years (QALYs), these health state utilities and AE disutilities were applied to the relative efficacy data. US-specific costs included those for CLL treatment, routine care and monitoring, AEs, disease progression (including subsequent treatment), and end-of-life care. Cost-effectiveness results are presented in terms of incremental cost per QALY. A new treatment that is both lower in total cost and more efficacious (in QALYs) vs. identified comparator treatments is described as being "dominant". Uncertainty in the model was tested through deterministic, probabilistic, and scenario analyses. RESULTS: The benefits in the cost-effectiveness model (CEM) were measured in terms of total discounted QALYs which were 6.47 for VenG, 6.12 for ClbG, 6.11 for IBR, 6.08 for IR, 6.41 for IG, and 5.98 for BR. The total discounted costs incurred by VenG and ClbG were $322,613 and $847,571, respectively. IBR-based treat-to-progression regimens incurred total discounted costs of $1,485,368 for IBR, $1,447,010 for IR, and $1,988,706 for IG. BR incurred total discounted costs of $808,756. Compared to these regimens, VenG is less costly (incremental cost ranges between: -$1,666,093 to -$486,143). The incremental discounted QALYs of VenG was: 0.36 vs. GC, 0.49 vs. BR, 0.37 vs. IBR, 0.06 vs. IG, and 0.39 vs. IR. Thus, VenG with a 12-month fixed duration, has lower total costs and is more efficacious ("dominant") over all comparators in the CEM. The probabilistic sensitivity analysis results were in line with the deterministic results. Sensitivity analysis indicated the post-progression survival utility was the most influential parameter on the model outcomes. As the CLL14 trial data matures, these cost-effectiveness estimates may change and additional scenarios for post-progression survival for VenG will be explored. Updated results will be presented. CONCLUSIONS: VenG is projected to be cost-effective vs. ClbG within accepted US cost-effectiveness thresholds. Compared with BR and IBR-based treat-to-progression regimens (IBR, IR, and IG), a 12-month fixed-duration treatment option with VenG seems cost saving and more efficacious based on the CEM. Taken together, VenG appears to be a cost-effective standard therapy for 1L CLL patients. Disclosures Davids: AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding. Ravelo:Genentech: Employment, Equity Ownership. Shapouri:Roche: Equity Ownership; Genentech, Inc.: Employment. Manzoor:AbbVie: Employment, Other: and may hold stock or stock options. Sail:AbbVie: Employment, Other: and may hold stock or stock options. Van de Wetering:AbbVie: Consultancy. Hallek:Roche, Gilead Sciences, Inc., Mundipharma, Janssen, Celgene, Pharmacyclics, AbbVie: Honoraria, Research Funding, Speakers Bureau.

Sequential Treatment with Bendamustine, Obinutuzumab (GA101) and Ibrutinib in Chronic Lymphocytic Leukemia (CLL): Final Results of the CLL2-BIG Trial of the German CLL Study Group (GCLLSG)

Sequential Treatment with Bendamustine, Obinutuzumab (GA101) and Ibrutinib in Chronic Lymphocytic Leukemia (CLL): Final Results of the CLL2-BIG Trial of the German CLL Study Group (GCLLSG)