Lower Total Cost of Care with Mosunetuzumab Compared with Alternative Novel Treatment Options in Third-Line or Later Relapsed/Refractory Follicular Lymphoma: A United States Third-Party Payer Perspective

Background: The treatment paradigm in third-line or later (3L+) relapsed/refractory (R/R) follicular lymphoma (FL) has evolved since 2020, with several novel treatment options approved by the United States (US) Food and Drug Administration. These treatments include: an enhancer of zeste homolog 2 inhibitor (tazemetostat); chimeric antigen receptor-modified T-cell therapies (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]); bispecific antibodies (mosunetuzumab, epcoritamab); and a Bruton’s tyrosine kinase inhibitor combination (zanubrutinib-obinutuzumab [ZO]). Data remain limited on the economic impact of these novel treatment options. The aim of this study was to evaluate the total cost of care (TCC) associated with different novel treatment options in 3L+ R/R FL from a US payer perspective.

Methods: A micro-economic analysis was conducted. Direct costs associated with the TCC per patient (including: cost of drug, wastage, administration, routine care, adverse events [AEs], and cytokine release syndrome [CRS] management) were evaluated on an annual basis, and cumulatively for up to 3 years. Drug costs were evaluated based on the wholesale acquisition cost (AnalysisSource^® July 2024) with respect to the mean duration of treatment (DOT) reported (or extrapolated from median to mean DOT by fitting exponential distribution) from each regimen’s pivotal trial (i.e. E7438-G000-101 for tazemetostat [NCT01897571; Morschhauser et al. Lancet Oncol 2020]; ZUMA-5 for axi-cel [NCT03105336; Jacobson et al. Lancet Oncol 2022]; TRANSCEND FL for liso-cel [NCT04245839; Morschhauser et al. Nat Med 2024]; ELARA for tisa-cel [NCT03568461; Fowler et al. Nat Med 2022]; GO29781 for mosunetuzumab [NCT02500407; Budde et al. Lancet Oncol 2022]; EPCOR NHL-1 for epcoritamab [NCT03625037; Linton et al. Lancet Haematol 2024]; and ROSEWOOD for ZO [NCT03332017; Zinzani et al. J Clin Onc 2023]). Drug wastage was estimated from the difference between vial size and actual dosage. Treatment administration costs were based on the schedule from each regimen’s pivotal trial and estimated per the Centers for Medicare and Medicaid Services (CMS) physician fee schedule. Routine costs were based on clinical expert opinion and the CMS physician and laboratory fee schedule. The cost associated with the management of Grade ≥3 AEs was estimated from the AE rates reported in each regimen’s pivotal trial with respect to the unit cost derived from the Healthcare Cost and Utilization Project. Costs associated with any grade CRS were evaluated based on the CRS rates reported in each regimen’s pivotal trial and clinical expert input on CRS management. All costs were adjusted to 2024 US Dollars.

Results: In Year 1, the TCC per patient was $544,193 for axi-cel, $532,384 for liso-cel, $504,966 for tisa-cel, $378,421 for epcoritamab, $286,796 for ZO, $246,369 for tazemetostat, and $210,322 for mosunetuzumab. In Year 2, the TCC per patient was $111,962 for ZO, $20,480 for tazemetostat, and $1,106 each for axi-cel, liso-cel, tisa-cel, epcoritamab, and mosunetuzumab. In Year 3, the TCC per patient was $1,106 for each novel treatment regimen. The cumulative TCC per patient up to 3 years was $546,405 for axi-cel, $534,596 for liso-cel, $507,178 for tisa-cel, $399,864 for ZO, $380,633 for epcoritamab, $267,955 for tazemetostat, and $212,534 for mosunetuzumab. Drug cost was the main driver in the TCC for all novel treatment options: 99% ($264,104 of $267,955) for tazemetostat; 96% ($383,718 of $399,864) for ZO; 92% ($349,795 of $380,633) for epcoritamab; 91% ($487,477 of $534,596) for liso-cel; 90% ($456,941 of $507,178) for tisa-cel; 89% ($189,113 of $212,534) for mosunetuzumab; and 85% ($462,000 of $546,405) for axi-cel. In comparison to the lowest TCC with mosunetuzumab ($212,534), the TCC over a cumulative 3-year time horizon was +$333,872 for axi-cel, +$322,062 for liso-cel, +$294,644 for tisa-cel, +$187,330 for ZO, +$168,099 for epcoritamab, and +$55,421 for tazemetostat.

Conclusions: In this study we quantified the varying economic ramifications of different novel treatment options for patients with 3L+ R/R FL, in terms of TCC per patient. Mosunetuzumab, a fixed-duration treatment option which can be administered in an outpatient setting, had the lowest cumulative TCC per patient up to 3 years, compared with alternative novel treatment options.