Cost-effectiveness of CAR-T cell therapy compared to bispecific T-cell engagers in Relapsed/Refractory multiple myeloma: A retrospective study using a markov model Free

Introduction: Multiple myeloma (MM) is considered an incurable malignancy, but with modern therapies, patients can achieve deep and durable remissions for extended periods. Immune therapies utilizing chimeric antigen receptor (CAR-T) T cells or bispecific T-cell engagers (BiTE) can induce durable remissions even in heavily pretreated patients. While experts favor giving CAR-T before BiTE, the high costs for a likely non-curative treatment limit its application in many healthcare systems, especially those outside of the U.S. With growing applications of CAR-Ts, it is of interest to understand their cost-effectiveness in alleviating MM morbidity and mortality. Here, we present a novel single-center cost-effectiveness analysis comparing idecabtagene vicleucel (ide-cel) to BiTE therapy at our center.

Methods:

We conducted a single-center retrospective study of patients with relapsed refractory multiple myeloma (RRMM), aged 18 to 85 years, treated with CAR-T or BiTE. The primary endpoint was the incremental cost-effectiveness ratio (ICER) between CAR-T and BiTE therapy. To simulate patients' outcomes post-treatment, we developed a Markov model using the TreeAge Pro software. This model incorporated various health states: healthy, disease, remission/response, progression, adverse events (including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and infections), and death. We used GraphPad Prism software to estimate survival probabilities. Lifetime costs, years of life gained, and ICER were calculated from the perspective of a U.S. payer, utilizing a willingness-to-pay threshold of $150,000 per quality-adjusted life year (QALY).

Results: We identified 61 patients with RRMM between January 2022 and September 2024, who had previously undergone an average of 5–9 lines of therapy, with an age range from 46 to 83 years, a mean of 68.5 years, with a predominance of males (76.6%). The cohort included 70% non-Hispanic whites and 26.6% African Americans. High-risk cytogenetics were observed in 40%, and 60% had R-ISS stage 2-3 disease. The median ECOG score was 1 (range 0–2).

31 patients received ide-cel, while 30 received BiTE (13 teclistamab-cqyv only, 7 talquetamab-tgvs only, 8 teclistamab-cqyv followed by talquetamab-tgvs, 2 elranatamab-bcmm). The median follow-up was 28 months for ide-cel and 18 months for BiTE. The median progression-free survival (PFS) was 14 months with ide-cel and 10 months with BiTE, showing no statistically significant difference (p=0.95; 95% CI: 0.73–2.68). Over a six-month period, the average inpatient and outpatient costs of ide-cel were $656,820 and $27,167, respectively, while for BiTE they were $49,196 and $145,567, respectively. The average length of hospitalization for ide-cel was 19.4 days (14–33 days) compared to 10 days (4–48 days) for BiTEs. Notably, three patients received BiTE ramp-up fully outpatient, which helped avoid inpatient costs.

We obtained QALY estimates for ide-cel and BiTE utilizing data from the KarMMa-3, MajesTEC-1, and MagnetisMM-3 studies and analyzing them with TreeAge Pro Software. The determined historic QALY was 1.75 for ide-cel and 1.26 for BiTE therapy. We calculated an ICER of $998,416 per QALY, meaning ide-cel can provide an additional 0.49 QALY at an incremental cost of $489,224 compared to BiTE. Considering the willingness-to-pay threshold of $150,000 per QALY, our analysis determined that transitioning from BiTE to CAR-T cell therapy for the treatment of RRMM is not cost-effective, particularly given the comparable PFS outcomes. Twenty-one months of treatment with BiTE is needed to equal the costs of ide-cel, and because the median PFS for this CAR-T was 14 months, patients in this arm will likely need treatment with BiTE later.

Conclusions:

Our innovative single-center analysis of the cost-effectiveness of CAR-T to BiTE reveals ide-cel as more expensive per year of PFS than BiTE therapy for the treatment of RRMM, with CAR-T manufacturing accounting for most of this cost. This difference in costs supports BiTE being more sustainable for many healthcare systems. Future directions that may promote an increased use of BiTE depend largely on whether most patients can receive this therapy entirely in the outpatient setting. This study lays the groundwork for larger studies where we will apply our comparative cost model to multicenter cohorts, including patients receiving other CAR-Ts such as Ciltacabtagene autoleucel.