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.

Shah:Bristol Myers Squibb: Consultancy; Jazz Pharmaceuticals: Consultancy; Eli Lilly: Consultancy; Kite Pharma: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; Adaptive Biotechnologies: Consultancy; Autolus, Beigene, Century Therapeutics, Deciphera, Jazz, Kite/Gilead, Pfizer, Precision Biosciences, Novartis, Takeda: Consultancy; Jazz Pharmaceuticals, Kite-Gilead, Servier: Research Funding; Pepromene Bio: Other: DSMB. Pantin:Omeros, Sanofi, BMS: Speakers Bureau; HCA Healthcare, Inc.: Current Employment; BMS, Omeros, Sanofi, Autolus, MaaT Pharma: Honoraria. Sandhu:Autolus: Consultancy. Jabbour:AbbVie, Adaptive Biotechnologies, Amgen, Astellas Pharma, BMS, Genentech, Incyte, Pfizer, Takeda: Consultancy; AbbVie, Adaptive Biotechnologies, Amgen, Ascentage Pharma Group, Pfizer, Takeda: Research Funding. Park:Takeda: Consultancy; Curocell: Current equity holder in publicly-traded company; Autolus, Fate Therapeutics, Genentech, InCyte, Servier, Sobi, Takeda (Institution): Research Funding; Adaptive Biotechnologies, Affyimmune, Allogene, Amgen, Artiva Biotherapeutics, Autolus, Bright Pharmaceutical Services, BMS, Caribou Biosciences, Curocell, Galapagos, Gilead Sciences, Intellia, In8Bio, Kite, Novartis, Pfizer, Servier, Sobi, Synthekine: Consultancy. Shaughnessy:BMS: Speakers Bureau; Sanofi: Speakers Bureau; Autolus, Sanofi: Consultancy. Abedi:BMS, Autolus: Consultancy; CytoDyn: Current holder of stock options in a privately-held company; AbbVie, BMS and Gilead Sciences: Speakers Bureau; Autolus, BMS and Gilead Sciences: Research Funding; Orca Bio: Research Funding. Bishop:Incyte: Honoraria; Achieve Clinics, Arcellx, Autolus, BMS, Chimeric Therapeutics, CRISPR Therapeutics, In8Bio, Iovance Biotherapeutics, Kite-Gilead, Optum Health, Novartis, Sana Biotechnology: Consultancy; Servier: Consultancy, Honoraria, Speakers Bureau; Sana Biotechnology: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Iovance Biotherapeutics: Consultancy; ADC Therapeutics: Honoraria, Speakers Bureau; GenMab: Honoraria, Speakers Bureau; Galapagos: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; In8bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Chimeric Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Meyer-Squibb: Consultancy, Honoraria, Speakers Bureau; Achieve Clinics, In8Bio: Current holder of stock options in a privately-held company; Arcellx, Autolus, Bristol-Myers Squibb, CRISPR Therapeutics, Lyell, Gilead Sciences and Novartis: Research Funding; AbbVie, ADC Therapeutics, Bristol-Myers Squibb, Gilead Sciences, Incyte, Novartis, Sanofi and Servier: Honoraria, Speakers Bureau. DeAngelo:Daiichi-Sankyo, Fibrogen: Other: DSMB; Mt Sinai MPN Consortium: Other: Mt Sinai MPN Consortium; AbbVie, Blueprint, GlycoMimetics, Novartis: Research Funding; Amgen, Autolus, Blueprint, Gilead, Incyte, Jazz, Novartis, Pfizer, Servier, Takeda: Consultancy; Dana-Farber Cancer Institute: Current Employment. Brugger:Autolus: Current Employment, Current equity holder in publicly-traded company. Brown:Autolus: Current Employment, Current equity holder in publicly-traded company. Patel:Autolus: Current Employment, Current equity holder in publicly-traded company. Roddie:Autolus, BMS, Gilead, Janssen: Consultancy; Autolus, BMS, Gilead: Honoraria, Speakers Bureau. Logan:Kite/Gilead: Research Funding; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Kadmon/Sanofi: Research Funding; Pharmacyclics: Research Funding; Kite: Consultancy; Pfizer: Consultancy; Talaris: Research Funding; Autolus: Research Funding; Sanofi: Consultancy; Amgen: Consultancy, Research Funding; Actinium: Consultancy; Astellas Pharma: Research Funding; Takeda: Consultancy.