ALBERT

Description: Introduction: Chimeric antigen receptor T (CAR-T) cell therapies targeting CD19 antigen can yield durable remissions in relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Yet the use of CAR-T can be limited by potentially severe toxicities, principally cytokine release syndrome (CRS) and neurologic toxicities. Management of neurologic toxicities requires vigilant monitoring, supportive treatment and resource allocation. We found no studies reporting healthcare costs associated with treatment-related neurologic adverse events (NEAEs) in r/r DLBCL patients. The objective of this study was to develop an evidence-based list of r/r DLBCL treatment-related NEAEs and to estimate the healthcare costs associated with these NEAEs in a real-world setting. Methods: Grade 3 or higher NEAEs that occurred in ≥2% of patients were identified by reviewing U.S. drug prescribing information (PI), European Medicines Agency summaries of product characteristics, and published clinical trials for treatments of r/r DLBCL. Then, adult patients ≥18 years old with r/r DLBCL were identified from a U.S. administrative claims database containing de-identified claims for over 150 million people across over 11 years. Patients were included if they had: 1) evidence of treatment beyond first-line (2L+) during the identification period (07/01/14 - 12/31/18); and 2) ≥1 inpatient or ≥2 outpatient claims for DLBCL (ICD-9-CM codes: 200.7X; ICD-10-CM codes: C83.3X) during the study period (01/01/14 - 12/31/18) with ≥1 having occurred prior to or on the date when the 2L+ treatment was received. 2L+ treatments were selected based on National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines and clinical expert input. To maximize the identification of patients treated with CAR-T, treatments were categorized hierarchically into 4 groups: CAR-T therapy (axicabtagene ciloleucel, or tisagenlecleucel), high-intensity cytotoxic therapy (carboplatin, cisplatin, cyclophosphamide, or ifosfamide), low-intensity cytotoxic therapy (bendamustine, lenalidomide, or gemcitabine), and targeted monotherapy (rituximab, ibrutinib, or brentuximab vedotin). The index date was defined as the start date of the 2L+ treatment. Patients in the cytotoxic and targeted therapy groups were also required to have evidence of an earlier line of cytotoxic or targeted therapy. All patients were required to have ≥6-months continuous enrollment before the index date. The outcomes of interest were the rates of NEAEs and total healthcare costs for patients with and without NEAEs during the 30-day post index period. Costs were inflated to 2018 US dollars. Descriptive statistics were reported. Results: Twenty-three NEAEs were identified based on the review: 17 for CAR-T, 10 for conventional immunochemotherapy regimens, and 4 for both. In the claims database, a total of 349 adult patients with r/r DLBCL were identified, including 27 CAR-T therapy, 262 high-intensity cytotoxic therapy, 50 low-intensity cytotoxic therapy, and 10 targeted therapy users. Mean (median, SD) patient age was 72.3 (73; 10.3) years, with 47.9% being female and 83.4% having Medicare insurance. Patients were mainly from the South (44.1%) and the Midwest (31.5%). The mean (SD) Charlson comorbidity index was 4.4 (3.6) and mean (SD) number of chronic conditions was 7.3 (2.2). Forty-five (12.9%) patients had ≥1 NEAE at some point during the 30-day post-index period. Of these, 14 (31.1%) were CAR-T users. Eleven (40.7%) of the CAR-T users had encephalopathy. Mean total healthcare costs were $99,611 higher for patients with NEAEs [mean (SD): $153,435 (227,771)] than those without any NEAEs [$53,824 (96,170)]. Among patients with NEAEs, 72% of the healthcare costs were accrued in the inpatient setting. Among patients without NEAEs, 63% of the healthcare costs were for outpatient medical services. The trend of higher costs in patients with NEAEs was consistent across treatment groups. Conclusion: This is the first study of the economic burden of NEAEs associated with treating r/r DLBCL in a real-world setting with data that reflects the current range of treatment options. Patients with r/r DLBCL who have NEAEs incur substantially higher costs than those without such events. In this analysis, CAR-T is overrepresented for NEAEs, although the sample size is small. We intend to repeat the analysis when more claims data becomes available in the near future. Disclosures Broder: Partnership for Health Analytic Research (PHAR), LLC: Other: I am an employee of the Partnership for Health Analytic Research (PHAR), LLC, which was paid by Novartis to conduct the research described in this abstract.. Ma:Novartis Pharmaceuticals Corporation: Employment. Yan:Partnership for Health Analytic Research (PHAR), LLC: Other: T. Yan is an employee of Partnership for Health Analytic Research (PHAR), LLC, a health services research company paid to conduct this research.. Chang:Partnership for Health Analytic Research (PHAR), LLC: Other: E. Chang is an employee of Partnership for Health Analytic Research (PHAR), LLC, a health services research company paid to conduct this research.. Eldjerou:Novartis Pharmaceuticals Corporation: Employment. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Kuzan:Novartis Pharmaceuticals Corporation: Employment. Zhang:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

Description: Introduction For patients (pts) with relapsed or refractory follicular lymphoma (r/r FL) beyond front-line therapy, there is no well-defined standard of care (SOC) treatment, especially in the third-line or later (3L+) setting. Treatment decisions for symptomatic patients depend on comorbidities, extent of disease, lines of prior therapy and duration of response to initial anti-CD20 containing treatment. Treatment options for 3L+ may include similar options to the ones in earlier lines, with a preference for non-cross-resistant schemes. Recently, a plethora of new compounds are being studied in clinical trials. A systematic literature review (SLR) was conducted to identify relevant evidence on clinical outcomes in pts with r/r FL, including conventional treatments and emerging compounds, within the 3L+ setting. Methods We performed a SLR on March 17, 2020. Clinical trials and observational studies were searched through Embase, PubMed, and Cochrane Central Register of Controlled Clinical Trials from 1998 to 2020, followed by relevant conference proceedings and regulatory documents. Evidence assessing any intervention as 3L+ FL and published in English language was included. If a study included broader indolent non-Hodgkin's lymphoma (iNHL) pts, only FL data was reported; if a study included pts with fewer than 3L+, 3L+ data was included, with mixed line results excluded. Conventional treatments, defined as approved or clinical guideline recommended treatments, included anti-CD20 monoclonal antibody (mAb)-containing regimen, mAb alone, chemotherapy alone, phosphatidylinositol 3-kinase (PI3K) inhibitors (idelalisib, copanlisib, duvelisib), lenalidomide + rituximab (R2), radio-immunotherapy (RIT) with yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, autologous and allogeneic stem cell transplantation (auto- and allo-SCT). Emerging compounds included new treatments that are not approved but were tested in the context of clinical trials (bruton tyrosine kinase inhibitors, bortezomib, polatuzumab vedotin, daratumumab, inotuzumab, bi-specific T-cell engaging CD19 mAb, anti-CD19 chimeric antigen receptor T-cell [CAR-T] therapy). Results Of the 3747 publications identified, 74 studies assessing 26 treatment regimens, including conventional ones like rituximab (R)-containing immunochemotherapy to emerging compounds such as CAR-T therapies, were selected. Across the conventional regimens, 7 studies reported clinical trial data with relatively large 3L+ FL populations (Table 1). With R monotherapy, PI3K inhibitors and tazemetostat, the reported complete response (CR) rates and overall response rates (ORR) ranged from 1-20% and 34-77%, while median duration of response (mDOR) ranged between 7.9-16.3 months. Three clinical trials with PI3K inhibitors reported proportions of pts achieving a response of at least 6 months in duration ranging from 18-30%; median progression-free survival (mPFS) ranging from 8.3-11.2 months. For tazemetostat, mPFS was 11.0 months in EZH2 mutant vs 5.7 months in wild-type FL. With allo-SCT, 2-yr PFS rate was 88% and 57% for pts with CR and PR, respectively. Overall survival (OS) data varied: median overall survival (mOS) was 28-38 months for PI3K inhibitors while mOS was up to 85 months after allo-SCT, despite high non-relapse mortality (NRM) rates with most common causes of death being graft-versus-host disease (GvHD) and infections. Safety profiles were also different across treatments, with most common side effects being hepatotoxicity, diarrhea and infections (PI3K inhibitors) to GvHD (allo-SCT). Three trials presented patient-reported outcomes (PRO) data, all using the Functional Assessment of Cancer Therapy (FACT) questionnaire. Two studies with PI3K inhibitors demonstrated favorable or clinically significant improvement on pts quality of life (QoL), but 1 allo-SCT trial did not show a significant difference between baseline and 2 years post-transplant scores. Conclusion To our knowledge, this is the first SLR focusing on 3L+ treatments of FL. Heterogeneity in study design, patient population, safety profile and reported outcomes make it challenging to identify an optimal treatment regimen for FL in the 3L+ setting. More PRO data are needed considering the important role pt QoL plays in treatment selection. Disclosures Ma: Novartis:Current Employment.Kaur:Novartis:Current Employment.Zhao:Novartis:Current Employment.Zhang:Novartis:Current Employment.Ramos:Novartis:Current Employment.Kumar:Novartis:Current Employment.John:Novartis:Current Employment.Bubuteishvili Pacaud:Novartis:Current Employment.Forcina:Novartis:Current Employment.