Эксплуатация и рентабельность электрошоковых терапий " Elranatamab Versus Technology " для лечения пациентов с тремя классами экспонатов, реплицированных и рефрактных множественных миелом, включая выбор лечения для других биологии и физики в Испании.

Key Summary Points

Introduction

Multiple myeloma (MM) is a haematological disease caused by the clonal proliferation of plasma cells in the bone marrow. This generates an increased production of monoclonal immunoglobulin (M-protein), which results in immunosuppression and significant organ damage, especially to blood, skeleton and kidneys [ 1 , 2 ]. MM has a significant impact on patients’ quality of life, with symptoms such as pain, fatigue, anaemia or, less commonly, renal dysfunction and hypercalcaemia [ 3 ].

MM is the second most common malignant neoplasia in Europe and Spain [ 4 , 5 ], with a 1-year prevalence of 5.9 cases per 100,000 people in the Spanish population [ 6 ], and its prevalence is expected to grow at a yearly rate of 2% [ 7 ].

Currently, MM remains an incurable disease, with a 5-year survival rate of between 47% and 60% [ 8 – 11 ]. In early treatment lines, disease prognosis has significantly improved with the incorporation of proteasome inhibitors (PIs), immunomodulatory drugs (IMIDs) and anti-CD38 monoclonal antibodies (mAbs) into therapeutic regimens. Although these treatment options have increased efficacy in these early treatment lines, patients with relapsed and refractory MM (RRMM) continue to have a poor prognosis [ 12 ]. Patients with triple-class exposed (TCE) MM, a subset of patients with RRMM, are those who have received at least three prior therapies, including one PI, one IMID and one anti-CD38 mAb. At present, patients with TCE-RRMM have typically received ≥ 3 prior lines of treatment, but with changing treatment algorithms the proportion of patients with TCE is expected to considerably increase in earlier lines of treatment [ 13 , 14 ]. In the real-world MAMMOTH study, median progression-free survival (PFS) was 2.8 months and median overall survival (OS) was 8.6 months for US patients with TCE MM receiving physician’s choice of treatment (PCT), with an overall response rate (ORR) of only 30%. In the real-world LocoMMotion study, the median PFS with PCT was 4.6 months, and the median OS was 12.4 months, with an ORR of only 29.8% [ 13 ].

The therapeutic management of patients with MM is generally based on the European Medical Oncology and Hematology Societies (EHA-ESMO) guidelines or other local recommendations [ 4 , 15 , 16 ]. Based on these guidelines, there is still a lack of clear standard of care for TCE-RRMM patients [ 13 , 14 ]. Within this setting, the primary therapies used are those based on PIs or IMIDs (as carfilzomib- or pomalidomide-containing regimens), usually combined with dexamethasone, or even with Anti-CD38 mAb therapies [ 13 , 14 ]. For patients with TCE-RRMM, effective options are limited, and targeting B-cell maturation antigen (BCMA) on myeloma cells offers a promising new approach. Elranatamab, a novel bispecific antibody targeting BCMA and CD3, was approved for the treatment of patients with TCE-RRMM based on the results from the MagnetisMM-3 study [ 17 , 18 ]. Long-term survival data from the study at 28.4 months of follow-up, reveal a median PFS of 17.2 months (95% confidence interval [CI] 9.8–not-estimable [NE]) and a median OS of 24.6 months (95% CI 13.4–NE). Among responders, the median duration of response was not yet reached, and the probability of maintaining response at 24 months was 66.9% (95% CI 54.4–76.7).

The relative efficacy of elranatamab was assessed in a matching-adjusted indirect comparison (MAIC) versus physician’s choice of treatment (PCT) in TCE-RRMM, based on LocoMMotion, the first prospective study of real-life standard of care in patients with TCE with RRMM. This study collected data from 248 patients mainly from Europe (90.7%), most of them with ECOG performance status of 0–1 and ≥ 3 prior lines of therapy. One important difference between MagnetisMM-3 and LocoMMotion was the proportion of patients with triple-class refractory (TCR) (97% in MagnetisMM-3 BCMA naïve cohort versus 74% in LocoMMotion). After adjusting by key variables, elranatamab was associated with significantly longer PFS (HR 0.32; 95% CI 0.30–0.47) and OS (HR 0.62; 95% CI 0.40–0.94).

Teclistamab, another BCMA‐CD3 bispecific antibody, was also recently approved for the treatment of patients with TCE-RRMM based on the MajesTEC-1 study [ 19 ]. In this case, another MAIC, assessing the relative efficacy of elranatamab versus teclistamab based on their pivotal trials, is available [ 20 ]. Key baseline characteristics were adjusted to be comparable between the two trials, since MagnetisMM-3 primarily enrolled patients with TCR disease while MajesTEC-1 only included patients who were TCE. In addition, MajesTEC-1 excluded patients with an ECOG PS of > 1. Once populations were balanced, elranatamab was associated with significantly longer PFS than teclistamab (HR 0.59; 95% CI 0.39–0.89). At 14.7-month median follow-up, median OS with elranatamab in MagnestisMM-3 was not reached, and at this point, elranatamab was associated with numerically longer OS than teclistamab, with a weighted OS HR of 0.66 (95% CI 0.42–1.03).

Based on the available information, the aim of this analysis was to inform healthcare national authorities with an evaluation of the efficiency of elranatamab compared with teclistamab and other available treatments used in Spanish clinical practice for patients with TCE-RRMM, taking the criteria of the Spanish National Health System (NHS) into consideration.

Materials and Methods

Model Description

A cost-effectiveness analysis was conducted through a partitioned survival model (PSM) with three health states: progression-free, post-progression and death.

The perspective of the Spanish NHS was taken, and a weekly cycle length was considered in the model. To capture clinical and economic effects derived from long-term patient evolution, a lifetime horizon was used (25 years) applying a discount rate of 3% for both future costs and outcomes [ 21 ].

The demographic characteristics of a hypothetical patient cohort were sourced from the MagnetisMM-3 Cohort A patient data since they were consistent with the Spanish population. Median age was 68.0 (range: 36–89) years, with 19.5% of the cohort older than 75 years. Of all patients, 63.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 2. Patients had received a median of five (range 2–22) prior lines of therapy, with 96.7% having triple-class refractory disease and 42.3% having penta-drug refractory disease. Additionally, general mortality was adapted as per the Spanish mortality data obtained from the National Institute of Statistics (INE).

Elranatamab was compared to a treatment basket representing the PCT based on the LocoMMotion study [ 13 ] and adapted to reflect the clinical setting in Spain at the time of the analysis (Electronic Supplementary Material [ESM] Table S1 ), and to teclistamab.

Input Parameters

Clinical Effectiveness and Safety

The proportion of patients in each health state at each time point was based on the efficacy of each treatment as measured by the PFS and OS curves, with the area between both curves being the post-progression survival (PPS). Since at the time of this analysis long-term survival data from MagnetisMM-3 were not available, data from the median follow-up of 14.7 months were used, as well as data from published matching-adjusted indirect comparisons (MAICs) of elranatamab versus PCT and teclistamab, respectively [ 20 , 22 ].

As clinical data did not cover the entire time horizon and extrapolations were needed, several parametric distributions (exponential, Weibull, Gompertz, lognormal, log-logistic, gamma and generalized gamma) were fitted to the clinical data obtained from MagnetisMM-3, assessing goodness-of-fit through the Akaike and Bayesian Information Criteria (AIC and BIC) and visual inspection of the resulting OS and PFS parametric fits for elranatamab (Fig. 1 ). Weibull distributions were used as the base case for both OS and PFS curves, and alternative distributions were explored in scenario analyses.

For each comparator (teclistamab and PCT), efficacy curves were obtained through the MAIC. If the proportional hazard (PH) hypothesis was acceptable, a hazard ratio (HR) was used to calculate relative efficacy values. Otherwise, efficacy curves were adjusted directly from the MAIC parameters. HRs were used for PCT and teclistamab OS (HR values 0.62 and 0.66, respectively) and for teclistamab PFS curves (HR value 0.59). The PH hypothesis was not acceptable for the PCT PFS curve and, therefore, it was adjusted directly from the MAIC parameters.

In addition to PFS and OS data, the duration of treatment (DoT) was also considered to take into consideration that a group of patients discontinued treatment before their progression due to other causes. This parameter affected solely cost results. Since only median DoT values were available for the different treatment options, DoT curves were built through exponential distribution adjusted to the median values reported in clinical trials (elranatamab 5.6 months; teclistamab 8.5 months; PCT 4.0 months) [ 13 , 18 , 23 ] (ESM Fig. S1 ). DoT curves were adjusted to PFS when necessary.

Treatment-related grade 3–4 adverse events (AEs) with a reported incidence of ≥ 5% in any of the comparators sourced from their respective clinical trials were included in the model [ 13 , 18 , 23 – 26 ]. Special interest AEs, namely ICANS (immune effector cell-associated neurotoxicity syndrome) and CRS (cytokine release syndrome), were also included regardless of grade and incidence for elranatamab and teclistamab (ESM Table S2 ). Treatment with tocilizumab was used for the management of both special interest AEs (ICANS and CRS) [ 18 , 19 ].

Additionally, given the high incidence of hypogammaglobulinaemia and infections during treatment with anti-BCMA bispecific antibodies, and following recent clinical recommendations, infection prophylaxis was considered for both options, elranatamab and teclistamab. Acyclovir administration was assumed for all alternatives, and intravenous immunoglobulin G was considered for elranatamab and teclistamab.

Quality of Life

Health utility values were derived from patient reported outcome data gathered from the MagnetisMM-3 trial for progression-free and post-progression health states and were used to calculate quality-adjusted life-years (QALYs) [ 27 ]. As utility values were collected from the EuroQoL five dimensions questionnaire (EQ-5D-5L), they had been mapped onto EQ-5D-3L through the Hernández Alava [ 28 ] method to follow the latest clinical recommendations [ 29 ], thereby providing utility values of 0.71 and 0.63 for progression-free and the post-progression health states, respectively. These utilities were applied to all treatments included in the analysis.

Healthcare Resource Use and Costs

The model included the healthcare resource use derived from the disease management for patients on each treatment, differentiating frequencies for progression-free and post-progression health states. All patients were assumed to make use of included resources. Treatment-specific resource use was sourced from clinical trial protocols [ 18 , 23 ], as shown in Table 1 .

Subsequent Treatments

The model assumed that 63.9% of patients progressing to the post-progression state receive a subsequent treatment, which was considered only for cost purposes, following the MagnetisMM-3 trial data. Subsequent treatment composition is based on the reported subsequent treatments observed in the MagnetisMM-3 trial and is a treatment basket which consists primarily of carfilzomib- and bortezomib-containing regimens (data on file). The same subsequent treatment was applied to all patients, regardless of their primary treatment.

Unit Costs

As the analysis adopted the perspective of the Spanish NHS, only direct costs (€ 2024) were considered. These include drug acquisition and administration costs, AEs and disease management costs (routine tests, physician’s office visits, imaging and biopsy tests, hospitalization).

Drug acquisition costs were expressed as ex-factory list prices [ 31 ], considering, when applicable, mandatory deductions established in Royal Decree-Law 8/2010 (Boletín Oficial del Estado [ 32 ]). Given that, in clinical trials, doses were sometimes reduced in the presence of AEs, relative dose intensity (RDI) was considered for each treatment based on the values reported during their respective clinical trials (78.35%, 93.35% and 93.70% for elranatamab, PCT and teclistamab, respectively) [ 18 , 23 , 33 , 34 ]. Vial wastage was assumed for all treatments. Drug costs for primary treatments were calculated following the DoT curves based on reported median values. Following established trial protocols and reported results, dosing regimen switches were considered when applicable for elranatamab and teclistamab (at 6 and 11.3 months after start of treatment, respectively) [ 18 , 24 ].

A one-off cost of €21,084.50 was included in the model to represent terminal care prior to death. This value was obtained from relevant sources for the Spanish setting and adjusted to 2024 € [ 35 ].

Drug acquisition and administration, AE management and healthcare resource use costs were obtained from relevant publications and official sources (ESM Table S3 ).

Finally, all inputs and assumptions used were validated by a panel of two haematologists, both of whom are MM experts from University Hospitals in Spain, through a multi-step process consisting of a written questionnaire, an in-person advisory board and a follow-up meeting for results validation.

Our research is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Sensitivity Analyses

Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the variables and determine the robustness of the results.

One-way sensitivity analysis (OWSA) was performed, modifying relevant model variables individually by ± 20% compared to the base-case values.

Scenario analyses were conducted by examining changes in some assumptions or data sources as opposed to those considered in the base case and assessing their impact on the results. Scenarios with different discount rates for future costs and outcomes (0% and 5%), dosing assumptions (vial sharing instead of wastage), efficacy modelling (different extrapolations for elranatamab OS and PFS curves), administration regimens (RDI set at 100% for all treatments), healthcare resource use (duration of hospitalization for initial elranatamab and teclistamab doses set to 3 days in both cases, instead of 6 days for teclistamab) and drug costs (net prices with 40–70% discounts off list prices, and applying spending caps [ 36 ]) were explored.

In the probabilistic sensitivity analysis (PSA), 1000 simulations were run, simultaneously varying all parameters within the uncertainties obtained from reported standard errors (SE) or 95% CI assuming normal distribution, and assuming a 10% SE when these were not available. The Cholesky decomposition was used to estimate the variability of survival curve parameters.

Results

Base Case Analysis

Results for the base case are shown in Table 2 . The use of elranatamab for patients with TCE-RRMM resulted in a total incremental cost of €17,860 over a lifetime horizon when compared with PCT. In terms of health outcomes, the treatment with elranatamab generated 0.93 additional life-years (LYs) and 0.72 additional QALYs. This results in an incremental cost-effectiveness ratio (ICER) of €24,754/QALY, which is within the willingness-to-pay (WTP) threshold commonly considered in Spain (€30,000/QALY).

In contrast, the use of elranatamab for patients with TCE-RRMM yielded savings of €101,026 per patient over a lifetime horizon in comparison with teclistamab. Regarding health outcomes, elranatamab provided 0.82 additional LYs and 0.60 additional QALYs. Therefore, elranatamab would be a dominant (less costly, more effective) therapeutic alternative compared with teclistamab.

Sensitivity Analyses

The sensitivity analyses confirmed the results observed in the base case. Elranatamab yielded cost-effective results in most analyses against PCT, while maintaining its dominance under all the deterministic analyses performed against teclistamab.

The results of the OWSA showed that elranatamab was cost-effective in most cases compared to PCT. Elranatamab remained dominant over teclistamab across all model variables that were individually modified. Efficacy-related variables, such as relative dose intensity and duration of treatment values, are the variables with the most impact in cost-effectiveness results of elranatamab versus both comparators. The results of the OWSA are presented in tornado diagrams (ESM Figs S2 , S3 ).

Similarly, regarding scenario analyses, the results of alternative scenarios were consistent with the base case ones (Table 3 ). The scenarios with the most impact on the results versus both comparators are the assumptions of 100% for all RDIs (which would increase the ICER of elranatamab versus PCT above the threshold, while retaining dominance against teclistamab), the use of net prices (which significantly lowers the ICER of elranatamab vs. PCT) and the use of best-fitting distributions for elranatamab OS and PFS simultaneously (lognormal and generalized gamma), which improved cost-effectiveness against PCT and maintained dominance versus teclistamab.

The results of the PSA are shown in an incremental cost-effectiveness plane (Fig. 2 ). The plane represents the incremental effectiveness in terms of QALYs of elranatamab versus PCT or teclistamab in the abscissas, and its incremental costs in the ordinates. The WTP threshold of €30,000/QALY has been included in order to highlight the cost-effective results area in the graph (in green).

Elranatamab maintained its cost-effectiveness versus teclistamab in 97.6% of simulations (and its dominance in 96.1%). Also, compared to PCT, elranatamab was cost-effective in 26.0% of simulations.

Discussion

Effective treatment options for advanced MM, especially TCE-RRMM, remain scarce. Current treatment options for these patients are primarily based on PI- or IMID-containing regimens, which offer poor results in this setting and are usually associated with significant healthcare resource utilization and disease management costs [ 10 , 13 , 14 ]. Therefore, more effective therapies are needed in advanced treatment lines to increase survival rates and alleviate the current clinical and economic burden associated to TCE-RRMM. In recent years, several novel alternatives, such as bispecific antibodies and CAR T-cell therapies, have been proved to be effective for these heavily pretreated patients.

In our cost-effectiveness analysis, the use of elranatamab was a cost-effective strategy versus both PCT and teclistamab, generating additional QALYs in both comparisons and savings when compared against teclistamab. The cost-effectiveness of elranatamab was not assessed versus CAR T-cell therapies as there was no published MAIC of elranatamab versus CAR T-cell therapies at the time of the analysis.

The base case results of our analysis reveal that elranatamab provides a clear gain in health outcomes versus both comparators, especially against PCT [ 13 ]. In the PSA, 99.4% and 97.8% of simulations versus PCT and teclistamab, respectively, show a positive incremental QALY value, which demonstrates the low uncertainty associated to health outcomes. The MagnetisMM-3 trial included a patient population with different characteristics that may be associated with a poorer prognosis than that of the populations in the MajesTEC-1 or LocoMMotion trials, such as the ECOG status or the proportion of patients with triple or penta-class refractory myeloma. Given the need to balance trial populations for comparing outcomes, the MAICs of elranatamab versus PCT and teclistamab, respectively, were used in our cost-effectiveness analysis [ 20 , 22 ]. Whilst the MAICs used in our analysis were conducted with data at a median follow-up of 14.7 months for elranatamab, long-term data from the MagnetisMM-3 and MajesTEC-1 trials are currently available [ 17 , 26 ]. Updated MAICs have been recently published with the latest clinical data available. In this updated analysis, compared with PCT, elranatamab (28.4-month follow-up) was associated with significantly longer PFS (HR 0.32, 95% CI 0.21–0.50, p ≤ 0.01) and OS (HR 0.50, 95% CI 0.33–0.78, p ≤ 0.01) [ 38 ], with respect to the data used in the present cost-effectiveness analysis (14.7-month follow-up: OS HR 0.62, 95% CI 0.40–0.94); these updated data would provide better cost-effectiveness results if incorporated into the analysis. In addition, a recent MAIC for teclistamab (22.8-month follow-up) versus PCT based on the LocoMMotion trial, is now also available [ 37 ]. After weighting for imbalances in baseline covariates, PFS (HR 0.48, 95% CI 0.35–0.64) and OS (HR 0.64, 95% CI 0.46–0.88) were significantly longer with teclistamab versus PCT [ 37 ].

Regarding the MAIC analysis of elranatamab versus teclistamab, data have been recently updated, with a median follow-up of 28.4 months for elranatamab and 30.4 months for teclistamab. In this case, elranatamab was associated with significantly longer PFS (HR 0.55, 95% CI 0.37–0.81, p < 0.05) and OS (base case HR 0.60, 95% CI 0.40–0.91, p < 0.05) than teclistamab [ 39 ], revealing a decrease of around 0.05 in the HR, for both PFS and OS, compared to the data considered in the present study.

With most uncertainty occurring in the cost variable, our cost-effectiveness analysis shows that, compared to PCT, treatment with elranatamab implies additional costs, resulting in an ICER below the WTP in the base case. Sensitivity and scenario analyses reveal some variability in costs, which can impact the overall direction of results versus PCT in a few scenarios, including the one testing potential discounts for the NHS and considering full doses instead of RDIs reported in clinical trials. Although the use of different RDIs for each comparator has a direct impact on costs, management of AEs that might have led to dose reductions are also accounted for in the model. On the other hand, it should be noted that the use of elranatamab would generate savings in comparison to teclistamab in the base case and in all sensitivity analyses performed. The differences in cost between elranatamab and teclistamab can be in part attributed to differences in dosing switch and in the DoT values between both alternatives.

In order to place our research in the context of economic evaluations in MM, we identified various systematic literature reviews (SLR) examining available cost-effectiveness evaluations in MM [ 40 – 43 ]. Most of the treatments included for comparison align with the definition of PCT in our analysis (as there is no standard of treatment and no individual comparisons were deemed relevant for our analysis), and none of them are novel therapies such as bispecific antibodies. Cost-effectiveness comparisons between these treatments often resulted in high ICER values, especially in more advanced treatment lines. However, variability between results was high due to the methodology used, assumptions and context, revealing the complexities of establishing clear and effective treatment pathways.

To our knowledge, our study is the first published cost-effectiveness analysis of elranatamab versus other treatments for TCE-RRMM in the European setting; also, no similar economic evaluations have been identified for other bispecific antibodies. However, the Canadian Agency for Drugs and Technologies in Health (CADTH) have recently published a cost-effectiveness analysis report comparing elranatamab against PCT and against cilta-cel, as a part of its elranatamab reimbursement recommendation report [ 44 ]. Elranatamab is compared against a PCT based on a Canadian Myeloma Research Group (CMRG) study and representing currently reimbursed and used therapies in the Canadian setting. PCT component therapies are mainly carfilzomib- or pomalidomide-containing regimens. Elranatamab resulted more effective than PCT, with slightly better incremental effectiveness results (QALYs) than our cost-effectiveness analysis, probably due to differences in the composition of both PCTs. In terms of costs, elranatamab was significantly more expensive than PCT; however, economic results cannot be directly compared to the ones we obtain, given the significant variability in costs between both settings and, more broadly, due to the large differences between the Canadian and the Spanish health systems.

Our study shows various limitations, some of them inherent to the nature of the long-term cost-effectiveness models, such as the need to extrapolate survival curves, or the simplification of the natural history of the disease into three health states. There are also limitations in relation to the assessment of the relative clinical effectiveness due to the lack of head-to-head comparisons. In this case, indirect comparisons were needed, with the inherent challenges of unanchored MAICs, where it is only possible to adjust for baseline characteristics that are mutually reported between trials. Nevertheless, analyses were conservatives and conducted according to National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) 18 guidance [ 45 ].

We also acknowledge limitations in the estimation of healthcare resource consumption and costs. Given the lack of real-world evidence describing healthcare resource utilization or AE management for elranatamab and comparators in the Spanish setting, these data had to be assessed based on experts’ clinical practice. General healthcare resource utilization rates are assumed to be equal for all comparators based on expert opinion, while clinical trial protocols have been used to inform treatment-specific resource use for both novel therapies. Although variations in these rates have shown minimal impact on overall results, possible differences in clinical practice could be expected. Furthermore, the estimated duration of treatment, or resource utilization for AE prophylaxis or management, have been sourced from clinical data and could also be subject to change in clinical practice. Thus, intravenous immunoglobulin (IGIV) administration, initially assumed only for a portion of patients being treated with bispecific antibodies, is likely to be administered to all patients under those therapies in clinical practice.

Moreover, there was uncertainty in the estimation of subsequent treatments and costs, which is a common limitation when assessing later treatment options with no clear recommendations. In this analysis, the same subsequent treatment cost was applied regardless of the primary treatment, which may not necessarily reflect the treatment patterns used in clinical practice for each primary treatment option, especially for the PCT arm, where subsequent treatment with idecabtagene vicleuce (ide-cel) is currently an option in Spain. In this context, further indirect evidence is needed in order to assess the impact in cost and health outcomes of this alternative.

Conclusion

This cost-effectiveness analysis demonstrates that elranatamab would be a cost-effective treatment in comparison to teclistamab and other therapeutic alternatives commonly used for the treatment of adult patients with TCE-MM in Spain, offering better effectiveness while generating potential cost savings.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 310 KB)

Author Contributions

All authors contributed to the development of the study. Virginia Lozano, Patrick Hlavacek, Julia Llinares, Sofía Toribio, David Carcedo and Jordi Asís-Montalt designed the analysis. David Carcedo and Jordi Asís-Montalt performed the model adaptation. Cristina Encinas and Joaquín Martínez-López constituted the panel of experts that validated model data. All authors contributed to validations of the results. The first draft of the manuscript was written by David Carcedo and Jordi Asís-Montalt. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This study was sponsored by Pfizer SLU, Madrid, Spain, which also funded the Rapid Service Fee. Medical writing and editorial support were provided by David Carcedo and Jordi Asís-Montalt of Hygeia and funded by Pfizer. David Carcedo and Jordi Asís-Montalt are employees of Hygeia, which received funding from Pfizer in connection with the development of this manuscript. Joaquín Martínez-López and Cristina Encinas were paid consultant to Pfizer in connection with the development of this manuscript.

Data Availability

All data used in this analysis are from public sources. For further model details please contact Virginia Lozano (virgina.lozano@pfizer.com).

Declarations

Conflict of Interest

Cristina Encinas has received honoraria derived from lectures and participation in advisory boards from Amgen, BMS, GSK, Johnson and Johnson, Menarini Stemline, Sanofi and Pfizer. Virginia Lozano, Patrick Hlavacek, Julia Llinares and Sofía Toribio are employees of Pfizer and may hold Pfizer stock. David Carcedo and Jordi Asís-Montalt are employees of Hygeia Consulting. Joaquín Martínez-López has received honoraria derived from research projects from Amgen, Incity, Janssen and Pfizer, and from lectures and participation in advisory boards from Amgen, BMS, Gilead, Incity, Janssen, Novartis, Pfizer and Roche.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Footnotes

Prior Presentation : Partial preliminary results of our research have been presented in the form of abstract and poster at the most recent annual congress of the Spanish Society of Hospital Pharmacists (SEFH) (17–19 October 2024, Coruña, Spain).

References

1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–60.

2. Dimopoulos MA, Richardson PG, Moreau P, Anderson KC. Current treatment landscape for relapsed and/or refractory multiple myeloma. Nat Rev Clin Oncol. 2015;12:42–54.

3. Brigle K, Rogers B. Pathobiology and diagnosis of multiple myeloma. Semin Oncol Nurs. 2017;33:225–36.

4. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32:309–22.

5. Sociedad Española de Oncología Médica. Las cifras del cáncer en España—2024. 2024. https://seom.org/images/publicaciones/informes-seom-de-evaluacion-de-farmacos/LAS_CIFRAS_2024.pdf . Accessed 30 Oct 2024.

6. GLOBOCAN. Cancer today. 2020. https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=724&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=0&include_nmsc_other=1 . Accessed 10 July 2023.

7. Kanas G, Clark O, Keeven K, Nersesyan K, Sansbury L, Hogea C. Estimate of multiple myeloma patients by line of therapy in the USA: population-level projections 2020–2025. Future Oncol. 2021;17:921–30.

8. SEOM (Spanish Society of Medical Oncology). Las cifras del cáncer en España—2023. 2023. https://seom.org/images/Las_cifras_del_Cancer_en_Espana_2023.pdf . Accessed 12 June 2024.

9. Kapinos KA, Hu E, Trivedi J, Geethakumari PR, Kansagra A. Cost-effectiveness analysis of CAR T-cell therapies vs antibody drug conjugates for patients with advanced multiple myeloma. Cancer Control. 2023;30:107327482211429.

10. Madduri D, Hagiwara M, Parikh K, et al. Real-world treatment patterns, healthcare use and costs in triple-class exposed relapsed and refractory multiple myeloma patients in the USA. Future Oncol. 2021;17:503–15.

11. National Cancer Institute. Cancer stat facts: myeloma. SEER. 2024. https://seer.cancer.gov/statfacts/html/mulmy.html . Accessed 30 Oct 2024.

12. Karampampa K, Zhang W, Venkatachalam M, Cotte F-E, Dhanda D. Cost-effectiveness of idecabtagene vicleucel compared with conventional care in triple-class exposed relapsed/refractory multiple myeloma patients in Canada and France. J Med Econ. 2023;26:243–53.

13. Mateos M-V, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia. 2022;36:1371–6.

14. Llinares J, Toribio S, García LF, et al. Treatment patterns of patients with multiple myeloma in Spain. How are triple-class exposed patients being managed? Conference communication. 10th World congress on controversies in multiple myeloma (COMy), 23-26 May 2024, Paris.

15. Grupo Español de Mieloma, Pethema. Guía de Mieloma Múltiple. 2021. https://www.fundacionpethema.es/sites/default/files/2024-04/Guia-Mieloma-Multiple-21-04-2021.pdf . Accessed 31 July 2024.

16. Aguilar Franco C, Bárez García A, Blum Domínguez A, et al. Hematoguía mieloma. 2024. https://www.sclhh.org/docs/pdf/consenso/guia%20mieloma%202024_version%20digital.pdf . Accessed 20 Nov 2024.

17. Tomasson MH, Iida S, Niesvizky R, et al. Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: update from the MagnetisMM-3 study. Hemasphere. 2024. 10.1002/hem3.136.

18. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29:2259–67.

19. van de Donk NWCJ, Garfall AL, Benboubker L, et al. Evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) to inform the management of patients (pts) treated with teclistamab in MajesTEC-1. J Clin Oncol. 2023;41:8033.

20. Mol I, Hu Y, LeBlanc TW, et al. A matching-adjusted indirect comparison of the efficacy of elranatamab versus teclistamab in patients with triple-class exposed/refractory multiple myeloma. Leuk Lymphoma. 2024;65:660–8.

21. Ministerio de Sanidad, Comité Asesor para la Financiación de la Prestación Farmacéutica del Sistema Nacional de Salud. Guía de evaluación económica de medicamentos. 2024. https://www.sanidad.gob.es/areas/farmacia/comitesAdscritos/prestacionFarmaceutica/docs/20240227_CAPF_Guia_EE_definitiva.pdf . Accessed 24 July 2024.

22. Mol I, Hu Y, LeBlanc TW, et al. A matching-adjusted indirect comparison of the efficacy of elranatamab versus physician’s choice of treatment in patients with triple-class exposed/refractory multiple myeloma. Curr Med Res Opin. 2024;40:199–207.

23. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495–505.

24. Usmani SZ, Karlin L, Benboubker L, et al. Durability of responses with biweekly dosing of teclistamab in patients with relapsed/refractory multiple myeloma achieving a clinical response in the MajesTEC-1 study. Conference communication. American Society of Clinical Oncology annual meeting, 2–6 June 2023, Chicago.

25. Sidana S, Moreau P, Garfall AL, et al. Long-term follow-up from MajesTEC-1 of teclistamab,a BCMA×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. Conference communication. European Hematology Association Congress, 8–11 June 2023, Frankfurt.

26. Tomasson M, Iida S, Niesvizky R, et al. Long-term efficacy and safety of elranatamab monotherapy in the phase 2 magnetismm-3 trial in relapsed or refractory multiple myeloma (RRMM). Blood. 2023;142:3385–3385.

27. Mohty M, Bahlis NJ, Nooka AK, DiBonaventura M, Ren J, Conte U. Impact of elranatamab on quality of life: patient-reported outcomes from MagnetisMM-3. Br J Haematol. 2024;204:1801–10.

28. Hernández Alava M, Pudney S, Wailoo A. Estimating the relationship between EQ-5D-5L and EQ-5D-3L: results from a UK population study. Pharmacoeconomics. 2023;41:199–207.

29. National Institute for Health and Care Excellence (NICE). NICE health technology evaluations: the manual. 2022. https://www.nice.org.uk/process/pmg36 . Accessed 10 July 2023.

30. Gisbert R, Brosa M. Healthcare cost database eSalud. Barcelona. 2018. http://www.oblikue.com/bddcostes/ . Accessed 29 Jan 2024.

31. Consejo General de Colegios Oficiales de Farmacéuticos. BOTPLUS. 2024. https://botplusweb.farmaceuticos.com/ . Access 31 Jan 2024.

32. Real Decreto-ley 8/2010, de 20 de mayo, por el que se adoptan medidas extraordinarias para la reducción del déficit público. Boletín Oficial del Estado. 2010. https://www.boe.es/buscar/doc.php?id=BOE-A-2010-8228 . Accessed 5 June 2023.

33. San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.

34. Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–34.

35. Nuño-Solinís R, Herrera Molina E, Librada Flores S, Orueta Mendía JF, Cabrera-León A. Actividad asistencial y costes en los últimos 3 meses de vida de pacientes fallecidos con cáncer en Euskadi. Gac Sanit. 2017;31:524–30.

36. Ministerio de Sanidad. BIFIMED: Nomenclátor. BIFIMED. 2024. https://www.sanidad.gob.es/profesionales/medicamentos.do . Accessed 30 Oct 2024.

37. Moreau P, Mateos M-V, Gonzalez Garcia ME, et al. Comparative effectiveness of teclistamab versus real-world physician’s choice of therapy in LocoMMotion and MoMMent in triple-class exposed relapsed/refractory multiple myeloma. Adv Ther. 2024;41:696–715.

38. Mol I, Hu Y, LeBlanc T, et al. Updated results of a matching-adjusted indirect comparison of elranatamab versus physician’s choice of treatment in patients with triple-class exposed/refractory multiple myeloma. Conference communication. American Society of Hematology Annual Meeting, 7–10 December 2024, San Diego.

39. Mol I, Hu Y, LeBlanc T, et al. Updated results of a matching-adjusted indirect comparison of elranatamab versus teclistamab in patients with triple-class exposed/refractory multiple myeloma. Conference communication. American Society of Hematology Annual Meeting, 7–10 December 2024, San Diego.

40. Chen W, Yang Y, Chen Y, Du F, Zhan H. Cost-effectiveness of bortezomib for multiple myeloma: a systematic review. ClinicoEcon Outcomes Res. 2016. 10.2147/CEOR.S104195.

41. Fu S, Wu C-F, Wang M, Lairson DR. Cost effectiveness of transplant, conventional chemotherapy, and novel agents in multiple myeloma: a systematic review. Pharmacoeconomics. 2019;37:1421–49.

42. Asrar MM, Lad DP, Prinja S, Bansal D. A systematic review of economic evaluations of treatment regimens in multiple myeloma. Expert Rev Pharmacoecon Outcomes Res. 2021;21:799–809.

43. Seefat MR, Cucchi DGJ, Dirven S, Groen K, Zweegman S, Blommestein HM. A systematic review of cost-effectiveness analyses of novel agents in the treatment of multiple myeloma. Cancers (Basel). 2021;13:5606.

44. Canadian Agency for Drugs and Technologies in Health. Elranatamab (Elrexfio): CADTH Reimbursement Recommendation. 2024]. Elranatamab (Elrexfio): CADTH reimbursement recommendation: indication: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. Accessed 21 Oct 2024.

45. Phillippo D, Ades T, Dias S, Palmer S, Abrams K, Welton N. NICE DSU technical support document 18: methods for population-adjusted indirect comparisons in submissions to NICE. 2016. https://research-information.bris.ac.uk/files/94868463/Population_adjustment_TSD_FINAL.com . Accessed 4 Nov 2024.

46. European Medicines Agency. EMA confirms recommendation for non-renewal of authorisation of multiple myeloma medicine Blenrep. 2023. https://www.ema.europa.eu/en/news/ema-confirms-recommendation-non-renewal-authorisation-multiple-myeloma-medicine-blenrep . Accessed 1 Aug 2024.

Associated Data

Supplementary Materials

Supplementary file1 (PDF 310 KB)

Data Availability Statement

All data used in this analysis are from public sources. For further model details please contact Virginia Lozano (virgina.lozano@pfizer.com).