Healthcare Resource Utilization and Costs Associated with Managing CRS and ICANS in Patients with Relapsed/Refractory Adult B-Cell Acute Lymphoblastic Leukemia Receiving Obecabtagene autoleucel (obe-cel)

Background: Chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) have dramatically improved survival outcomes but are associated with high rates of adverse events (AEs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), contributing to increased healthcare costs associated with this treatment modality. Obe-cel is an autologous CD19-directed CAR T-cell therapy with a differentiated fast off-rate CD19 binding domain, a 4-1BB co-stimulatory domain and tumor burden-guided dosing, designed with the potential to improve persistence and reduce toxicity. Currently, there is a paucity of research documenting the costs related to managing CRS/ICANS among patients with R/R B-ALL treated with CAR T-cell therapy. This analysis evaluated healthcare resource utilization (HCRU) and estimated costs of managing CRS and/or ICANS events by grade in patients with R/R B-ALL who received obe-cel treatment in the FELIX study.

Methods: FELIX (NCT04404660) is an open-label, multi-center, global, single-arm Phase Ib/II study evaluating the safety and efficacy of obe-cel in adult patients with R/R B-ALL. A secondary analysis was conducted to evaluate HCRU as a result of CRS and ICANS, and estimate the overall costs for managing these AEs among patients with R/R B-ALL. HCRU for patients with treatment-emergent CRS and/or ICANS was monitored for 6 months post obe-cel administration. Results were stratified by, and specific to, AE type (non-overlapping CRS or ICANS, and overlapping CRS and ICANS) and grade. CRS AEs were graded per ASTCT/ASBMT 2019 CRS consensus grading and NCI-CTCAE v5.0; ICANS AEs were graded per ASTCT/ASBMT 2019 consensus criteria. Costs associated with managing CRS and/or ICANS were estimated using a micro-costing methodology: 1) AE-specific HCRU from the time of AE onset through resolution was identified for patients in the FELIX study; 2) the most recently available unit costs sourced from public databases or literature (US Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, and Merative™ Micromedex^® RED BOOK^®) were applied to each HCRU and adjusted to 2023 US dollars using the consumer price index. Key HCRU captured for each AE included hospitalizations (standard inpatient and intensive care unit [ICU]), length of stay, office visits, laboratory and imaging, procedures (e.g. dialysis, mechanical ventilation), and pharmacy (e.g. oncology supportive care, prophylactics). HCRU was reported as event-level utilizations unless otherwise stated. Data cut-off for this analysis was 13 September 2023.

Results: In FELIX, 127 patients received obe-cel, of whom 88 (69.3%) experienced a CRS and/or ICANS AE. Of these 88 patients, 47.7% were male, 70.5% were white, 59.1% were not Hispanic or Latino, and mean (standard deviation) age was 48.6 (16.7) years. Overall, a total of 102 CRS and/or ICANS AEs were reported: 72 (70.6%) were CRS only, 13 (12.7%) ICANS only, and 17 (16.7%) overlapping CRS and ICANS. Few patients (n=11) experienced Grade ≥3 CRS and/or ICANS AEs. There were three non-overlapping CRS AEs, three non-overlapping ICANS AEs, and six overlapping CRS and ICANS AEs with at least one AE (CRS or ICANS) of Grade ≥3. Mean AE duration was shorter for Grade <3 vs Grade ≥3 AEs (7.5 vs 19.8 days, respectively). Overlapping CRS and ICANS AEs had the highest mean total costs followed by ICANS only and CRS only events. The mean cost for treating a patient with Grade ≥3 vs Grade <3 CRS and/or ICANS was $44,298 vs $7,464 (~6-fold increase in cost for Grade ≥3 events). Medication usage (in particular tocilizumab) and hospitalization/ICU costs were key drivers of overall CRS and/or ICANS management costs (64.2% and 27.1%, respectively). Most events did not include an inpatient or ICU hospitalization.

Conclusions: Grade ≥3 CRS and/or ICANS AEs are associated with increased HCRU, but these events were rare in the FELIX study. Obe-cel is designed to improve efficacy and decrease toxicity through use of a novel targeting construct and tumor burden-guided split dosing, offering a potential solution to optimize utilization of resources and reduce costs associated with CAR T-cell therapy for patients with B-ALL.