Healthcare Resource Utilization and Cost of Cytokine Release Syndrome and Neurotoxicity in Patients with Relapsed and Refractory Multiple Myeloma Receiving the BCMA-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121) in the KarMMa Trial

Introduction: Relapsed and refractory multiple myeloma (RRMM) is associated with poor prognosis. Autologous chimeric antigen receptor (CAR) T cell therapies have emerged as a potential single-infusion treatment option for these patients, but are associated with 2 potentially serious adverse events (SAEs): cytokine release syndrome (CRS) and neurologic events (NEs). Evidence on healthcare resource utilization (HCRU) and costs associated with management of these SAEs is limited. Idecabtagene vicleucel (ide-cel, bb2121), is a CAR T cell therapy in development for patients with RRMM who are triple-class exposed to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies in the KarMMa trial. The objective of this study was to estimate the cost of CRS and NE management for patients with RRMM who received ide-cel in the KarMMa trial (NCT03361748).

Methods: HCRU occurring from onset to resolution of CRS and/or NE were identified from the KarMMa trial database. A micro-costing methodology was used to estimate costs. HCRU included length of stay (LOS) in hospital (number of standard inpatient [IP] days and intensive care unit [ICU] days), diagnostics (e.g. lab work and imaging), procedures (dialysis and intubation), and medications. Only HCRU consistent with trial management guidelines was included in the analysis. Unit costs were applied to each HCRU from the US health system (provider) perspective and were adjusted to 2020 USD. Cost per IP day (USD 2,542) was estimated from Healthcare Cost and Utilization Project (HCUP) Databases, and cost per ICU day (USD 7,556) was sourced from the literature (Dasta JF, et al. Crit Care Med 2005;3:1266-71). Medication cost data were obtained from REDBOOK^TM using wholesale acquisition costs and were uniformly applied across sites of care. Diagnostic, transfusion, and procedure costs were taken from the Centers for Medicare & Medicaid Services lab fee schedule, physician fee schedule, or outpatient prospective payment system. For patients administered outside of the USA, any HCRU inconsistent with US clinical practice was adapted to reflect the US cost perspective (e.g. metamizole, a prohibited medication in the USA, was substituted with the cost of acetaminophen). Unit costs were estimated by applying a payment-to-cost ratio to any Medicare reimbursement rates. Costs were adjusted to reflect cost to the site of care where the HCRU occurred by applying cost ratios from the literature (Meisenberg BR, et al. Bone Marrow Transplant 1998;21:927-32; Winfield L, Muhlestein D. Leavitt Partners; 2017). Costs were aggregated for the duration of events and presented by HCRU category, specifically diagnostic, drugs, procedure, and facility costs. Descriptive statistics were used to summarize the data.

Results: Of the 128 patients treated with ide-cel in the KarMMa trial, 107 (83.6%) had CRS with or without NE, 84 (65.6%) had CRS only, and 23 (18.0%) had both CRS and NE, and no patients had isolated NE. Most patients (96/107 [89.7%]) with CRS and/or NE had an AE grade ≤ 2 (maximum); none had both CRS and NE grade ≥ 3. CRS occurred before or on the same day as NE in 95.6% of the 23 patients with both SAEs. Among the 15 patients in whom CRS occurred first, NE developed a median of 2 days after CRS onset. HCRU and LOS for AE management, including IP and ICU days, are shown in the Table. Of the 107 patients with CRS with or without NE, 67 (62.6%) received tocilizumab, 26 (24.3%) received both tocilizumab and corticosteroids, 7 (6.5%) received vasopressors, and 19 (17.8%) were admitted to the ICU for AE management. Five patients (4.7%) required dialysis or intubation and all had grade ≥ 3 events. Median total LOS ranged from 6 to 30 days, with IP stay accounting for the majority. Median costs ranged between USD 18,497 and USD 23,285 for CRS grade ≤ 2, USD 33,183 for CRS grade ≤ 2 with NEs, and USD 60,588 and USD 121,535 for CRS grade ≥ 3 with or without NE (Figure). Costs were mainly driven by hospitalization; namely IP and ICU LOS which ranged between USD 15,252 and USD 106,346. Median costs overall for patients with CRS grade ≤ 2 versus grade ≥ 3 CRS with or without NEs were USD 21,693 versus USD 99,894.

Conclusions: For triple-class exposed patients with RRMM receiving ide-cel in the KarMMa trial CRS or NE observed were primarily grade ≤ 2. More severe CRS or NEs was associated with increased HCRU and management costs, particularly grade ≤ 2 versus grade ≥ 3.