Abstract
Introduction: The advent of chimeric antigen receptor (CAR) T-cell therapy has represented one of the most innovative therapeutic advances in oncology in recent years. Impressive clinical responses to CAR T-cell therapy observed in patients in clinical trials have led to the Food and Drug Administration (FDA) approval of five CAR T-cell therapies in the US since 2017 to treat large B-cell, mantle cell, and follicular lymphomas, as well as acute lymphoblastic leukemia (ALL) and multiple myeloma. The first two CAR T-cell therapies approved by the FDA, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), have now been on the US market for the treatment of patients with large B-cell lymphoma (LBCL) since 2017 and 2018, respectively, allowing for assessment of their use in real-world clinical practice. Given the complex logistics of the manufacturing, distribution, administration and unique toxicity of CAR T-cell therapies, initial use was limited to larger centers with prior experience with CAR T-cell therapy clinical trials. With greater use and availability of multiple CAR T-cell therapies, real-world evaluation of the clinical profiles, treatment patterns, and outcomes of LBCL patients treated with CAR T-cell therapies may inform clinical, regulatory, and drug development decision making, ultimately helping to improve patient outcomes. This real-world claims-based study aimed to describe characteristics and treatment outcomes of patients with diffuse LBCL (DLBCL) treated with the CAR T-cell therapies axi-cel or tisa-cel in the non-trial setting.
Methods: Patients with at least 1 claim for axi-cel or tisa-cel made prior to 03/31/21 and a diagnosis code of DLBCL were identified from the Symphony Integrated Dataverse (IDV), a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 63% of prescriptions with full lifecycle data, 62% of medical claims, and 25% of hospital claims volume in the US. Patients were excluded from analysis if axi-cel or tisa-cel was the first therapy identified for the patient since diagnosis of DLBCL within the claims database, if treatment was received as a part of a clinical trial, if there were no supporting claims around CAR T-cell therapy in the claims database, if next line of therapy was received within 30 days of a sole claim for axi-cel or tisa-cel, or if data supported a diagnosis of ALL. Patient characteristics and treatment patterns were summarized using descriptive statistics.
Results: Among a total of 88 eligible patients with DLBCL identified in this study, 52% (n=46) received axi-cel and 48% (n=42) received tisa-cel.
At the time of treatment with axi-cel or tisa-cel therapy, median patient age was 63 years (range, 20-78 years) and commercial insurance was the primary payer for 83% of patients (n=73). The majority (n=59, 67%) of patients were male. Patients with DLBCL treated with axi-cel or tisa-cel were distributed across each of the 4 US census regions, with 27% from the Northeast, 11% from the South, 32% from the Midwest, and 30% from the West. .
Axi-cel or tisa-cel was received a median of 14 months following patients' initial diagnosis of DLBCL and for the majority (n=54, 61%) of patients, axi-cel or tisa-cel-related claims were associated with administration of CAR T-cell therapy in the outpatient setting (Table). Prior to axi-cel or tisa-cel, 57% of patients (n=50) received 2 or more lines of systemic therapy. Within a median follow-up period of 7.8 months, 17% of patients (n=15) received systemic therapy following axi-cel or tisa-cel treatment.
Conclusions: In the first few years of US market availability, the CAR T-cell therapies axi-cel and tisa-cel have been used to treat patients with LBCL outside of the clinical trial setting. While the majority of patients in this real-world claims-based study received axi-cel or tisa-cel in an outpatient setting, hospital claims are underrepresented in the database utilized. Despite short follow-up (less than 8 months from initiation of these CAR T-cell therapies), approximately one in 6 patients appear to have relapsed disease, based on the need for subsequent systemic therapy. Further research is warranted to understand real-world clinical outcomes among patients treated with CAR T-cell therapy outside the trial setting.
Zimmerman Savill: Roche/Genentech: Ended employment in the past 24 months; Cardinal Health: Current Employment. Klink: Cardinal Health: Current Employment, Current holder of stock options in a privately-held company. Liassou: Cardinal Health: Current Employment. Chopra: Cardinal Health: Current Employment. Laney: Cardinal Health: Current Employment. Gajra: Cardinal Health: Current Employment, Current equity holder in publicly-traded company.
