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Current hematologic malignancy reports · 2025

Навигация экономического бремени множественной миеломы: понимание экономической эффективности терапии CAR-T и биконкретной антителной терапии.

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Keesari PR, Samuels D, Vegivinti CTR, Pulakurthi YS, Kudithi R, Dhar M, Janakiram M

Аннотация

Цель обзора Multiple mieloma - хроническая злокачественность, и с учетом изменяющихся вариантов лечения понимание экономического бремени и экономической эффективности лечения имеет решающее значение для врачей и исследователей. В этой связи мы рассматриваем недавнее утверждение биконкретных антител и CAR-T для миэломы и их финансовые последствия, включая прямые и косвенные издержки. Мы сравниваем это с нынешними режимами и представляем в настоящем обзоре сопоставление затрат. Мы пришли к выводу о том, что использование более эффективных методов лечения, таких, как CAR-T, в более ранних направлениях лечения может быть более эффективным с точки зрения затрат в зависимости от страны и используемой модели. Дальнейшие исследования имеют важнейшее значение для более глубокого понимания экономической эффективности биконкретных антител, включая сопоставления между головой и головой, и терапией CAR-T.
Оригинал публикации

Navigating the Economic Burden of Multiple Myeloma: Insights into Cost-effectiveness of CAR-T and Bispecific Antibody Therapies.

Purpose of reviewMultiple myeloma is a chronic malignancy and with evolving treatment options, understanding the economic burden and cost-effectiveness of therapies is crucial for clinicians and researchers.Recent findingsIn this, we review the recent approval of Bispecific antibodies and CAR-T for myeloma and their cost implications, including direct and indirect costs. We compare this to current regimens and provide cost comparisons in this review. We conclude that the use of more effective therapies such as CAR-T in earlier lines of therapies may be more cost-effective depending on the country and model used. Further studies are essential to better understand the cost-effectiveness of bispecific antibodies including head-to-head comparisons to CAR-T therapy.

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Introduction

Multiple myeloma is a hematologic malignancy with clonal proliferation of plasma cells in bone marrow leading to monoclonal immunoglobulin overproduction and end organ damage. The incidence of multiple myeloma and associated mortality is growing in the U.S with an average lifetime risk of acquiring the disease being around 1 in 100 and overall survival rate of 57% [ 1 ]. The average years of life lost to multiple myeloma ranges from 30 years in younger individuals to an overall average of 16.8 years [ 2 ]. Multiple myeloma is not only associated with high morbidity and mortality but also imposes a significant economic burden on patients. Prior studies analyzing the economic burden in multiple myeloma patients reported a total cost utilization ranging from 20 to 40 thousand US dollars per patient per month (PPPM) with around 50%—85% being related to multiple myeloma and even higher costs in those exposed to multiple classes of drugs [ 3 – 6 ]. The monthly costs incurred also showed rising trends over the years in these studies. Given significant restrictions and treatment related adverse effects of bone marrow transplantation, multiple newer treatments like immunotherapies have emerged for use in multiple myeloma patients, especially those that have been exposed to multiple (≥ 4) prior classes of drugs. Chimeric antigen receptor T cell (CAR-T) therapy involves genetically modifying patients' T cells to recognize tumor antigens. Bispecific antibodies are drugs that bind to two different antigen sites simultaneously, typically CD3 of T cells and tumor antigens (BCMA/FCRh5/GPRC5D) of the myeloma cells enhancing anti-tumor activity of host immune cells. Since its approval for use CAR-T (2021) and bispecific antibodies (2022) have significantly improved survival in triple class refractory and penta-class refractory multiple myeloma patients [ 7 , 8 ]. Given heightened healthcare costs, it is important to understand the economic burden and cost-effectiveness of newer therapeutic agents in multiple myeloma patients. In this review we have focused on the economic aspects of use of CAR-T therapy and bispecific antibodies in multiple myeloma patients.

Economic Burden of Multiple Myeloma

Direct Costs

Direct costs associated with multiple myeloma treatment are expenses related to drugs, hospitalizations, physician visits, lab work, imaging studies, and other supportive care.

Drug Cost

The cost of most drugs used in multiple myeloma is approximately 100,000 dollars per year and combination regimens with a Proteosome inhibitor, immunomodulatory agent, and an anti CD-38 targeted monoclonal antibody costs 300,000—600,000 US dollars per year [ 9 ]. This cost is expected to rise with disease progression and exposure to multiple classes of drugs. Yang et al. in a retrospective cohort study of 1,521 patients with multiple myeloma of which 66.8% were double class exposed (DCE) and 33.2% were Triple class exposed (TCE) identified that the overall mean total all-cause health care costs were $20,338 PPPM (85% MM-related) of which drug cost accounted to $11,435 PPPM. The drug cost in DCE vs TCE was $9,854 vs $16,117 PPPM and drug cost was the overall cost driver in both populations [ 3 ]. In an analysis by Hollmann et al. evaluating the cost burden of relapsed or refractory MM patients treated with triplet regimens over 1 year suggested that the average monthly cost per patient per triplet regimen ranged from $13,784 to $30,657. The study also reported that drug acquisition and treatment duration accounted for the cost of treatment [ 4 ]. A study based on 600 multiple myeloma patients receiving treatment in Singapore found that daratumumab based regimens were more expensive than bortezomib based regimens due to unit cost difference but after comparing treatment costs for post progression treatment regimens, patients incurred higher costs following first line bortezomib based regimen than daratumumab [ 10 ]. Use of the most effective regimen early in the disease course and use of maintenance therapy after first line treatment to delay progression although may incur higher drug costs but have been found to lower overall costs during the disease course [ 11 – 13 ]. Prior studies have also reported that transitioning treatment in multiple myeloma patients to home-based setting for drug infusions is cost-effective and helps patients spend more time with family [ 14 , 15 ]. In Table 1 we summarize the drug costs of different lines of therapy for patients with Multiple Myeloma. Table 1 Drug costs of different lines of therapy for Non-Transplant Eligible Multiple Myeloma Patients Line of Therapy Treatment regimen a Approximate Annual Drug Cost for the regimen (USD) b, c Chemotherapy regimens 1st Line VRd Bortezomib—$2,159 Lenalidomide—$239,369 Dexamethasone—$574 Total—$242,102 1st Line DRd Daratumumab—$165,227 Lenalidomide—$239,369 Dexamethasone—$574 Total—$405,170 1st Line KRd Carfilzomib—$173,090 Lenalidomide—$239,369 Dexamethasone—$574 Total—$413,033 1st Line VCd Bortezomib—$2,159 Cyclophosphamide—8,087 Dexamethasone—$574 Totak—$10,820 1st Line D-VRd Daratumumab—$165,227 Bortezomib—$1,871 Lenalidomide—$239,369 Dexamethasone—$575 Total—$407,042 1st Line D-KRd Daratumumab—$165,227 Carfilzomib—$173,090 Lenalidomide—$239,369 Dexamethasone—$575 Total—$578,261 2nd Line KCd Carfilzomib—$173,090 Cyclophosphamide—$8,087 Dexamethasone—$574 Total—$181,752 2nd Line DVd Daratumumab—$165,227 Bortezomib—$2,158 Dexamethasone—$574 Total—$167,960 2nd Line SVd Selinexor—$441,648.00 Bortezomib—$2,158 Dexamethasone—$574 Total—$444,381 CAR-T 2nd Line Cilta-Cel $507,687 3rd Line Ide-Cel $503,455 T-cell engagers 5th line Belantamab $371,658 5th line Elranatamab $486,506 5th line Teclistamab $234,963 5th line Talquetamab $372,380 a—VRd: Bortezomib, Lenalidomide, and Dexamethasone; DRd: Daratumumab, Lenalidomide, and Dexamethasone; KRd: Carfilzomib, Lenalidomide, and Dexamethasone; DVd: Daratumumab, Bortezomib, and Dexamethasone; SVd: Selinexor, Bortezomib, and Dexamethasone; VCd: Bortezomib, Cyclophosphamide, and Dexamethasone; D-VRd: Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone; D-KRd: Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone; Melphalan flufenamide: Melphalan flufenamide and Dexamethasone; Ide-cel: Idecabtagene vicleucel; Cilta-Cel: Ciltacabtagene autoleucel; Belantamab: Belantamab mafodotin; Selinexor: Selinexor and Dexamethasone; b—Costs calculated using CMS payment limits (Average Sale Price (ASP) plus 6% or wholesale acquisition cost plus 3% when ASP is not yet established) for parenteral drugs and AWP (average wholesale price) for oral medications; Usual recommended dosing without accounting for dose reductions and standard 70 kg, 1.73 m2 body surface area were used for the cost calculations c— https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files ; https://www.micromedexsolutions.com/micromedex2/librarian/CS/E7AABD/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/ED8554/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/redbook.FindRedBook?navitem=topRedBook&isToolPage=true ;

Table 1
Drug costs of different lines of therapy for Non-Transplant Eligible Multiple Myeloma Patients
a—VRd: Bortezomib, Lenalidomide, and Dexamethasone; DRd: Daratumumab, Lenalidomide, and Dexamethasone; KRd: Carfilzomib, Lenalidomide, and Dexamethasone; DVd: Daratumumab, Bortezomib, and Dexamethasone; SVd: Selinexor, Bortezomib, and Dexamethasone; VCd: Bortezomib, Cyclophosphamide, and Dexamethasone; D-VRd: Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone; D-KRd: Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone; Melphalan flufenamide: Melphalan flufenamide and Dexamethasone; Ide-cel: Idecabtagene vicleucel; Cilta-Cel: Ciltacabtagene autoleucel; Belantamab: Belantamab mafodotin; Selinexor: Selinexor and Dexamethasone; b—Costs calculated using CMS payment limits (Average Sale Price (ASP) plus 6% or wholesale acquisition cost plus 3% when ASP is not yet established) for parenteral drugs and AWP (average wholesale price) for oral medications; Usual recommended dosing without accounting for dose reductions and standard 70 kg, 1.73 m2 body surface area were used for the cost calculations c— https://www.cms.gov/medicare/payment/part-b-drugs/asp-pricing-files ; https://www.micromedexsolutions.com/micromedex2/librarian/CS/E7AABD/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/ED8554/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/redbook.FindRedBook?navitem=topRedBook&isToolPage=true ;

Line of TherapyTreatment regimen aApproximate Annual Drug Cost for the regimen (USD) b, c
Chemotherapy regimens
1st LineVRdBortezomib—$2,159 Lenalidomide—$239,369 Dexamethasone—$574 Total—$242,102
1st LineDRdDaratumumab—$165,227 Lenalidomide—$239,369 Dexamethasone—$574 Total—$405,170
1st LineKRdCarfilzomib—$173,090 Lenalidomide—$239,369 Dexamethasone—$574 Total—$413,033
1st LineVCdBortezomib—$2,159 Cyclophosphamide—8,087 Dexamethasone—$574 Totak—$10,820
1st LineD-VRdDaratumumab—$165,227 Bortezomib—$1,871 Lenalidomide—$239,369 Dexamethasone—$575 Total—$407,042
1st LineD-KRdDaratumumab—$165,227 Carfilzomib—$173,090 Lenalidomide—$239,369 Dexamethasone—$575 Total—$578,261
2nd LineKCdCarfilzomib—$173,090 Cyclophosphamide—$8,087 Dexamethasone—$574 Total—$181,752
2nd LineDVdDaratumumab—$165,227 Bortezomib—$2,158 Dexamethasone—$574 Total—$167,960
2nd LineSVdSelinexor—$441,648.00 Bortezomib—$2,158 Dexamethasone—$574 Total—$444,381
CAR-T
2nd LineCilta-Cel$507,687
3rd LineIde-Cel$503,455
T-cell engagers
5th lineBelantamab$371,658
5th lineElranatamab$486,506
5th lineTeclistamab$234,963
5th lineTalquetamab$372,380

Healthcare Utilization

Yang et al. reported overall MM-related emergency department visits, outpatient physician office visits, other outpatient visits, visit for outpatient prescriptions, and hospitalizations PPPM were 0.05, 3.22, 4.19, 0.89, and 0.10 respectively with median length of hospital stay being 1.02 days PPPM [ 3 ]. The study also reported that the proportion of patients with at least 1 MM-related ED, outpatient, and inpatient visit during the study period were 22%, 55%, and 99% respectively and that healthcare resource utilization was higher in TCE than DCE population even though TCE population had shorter follow-up period. Gupta et al. queried a commercial insurance database between 2016 to 2021 to identify 1492 patients with multiple myeloma on therapy. They had reported that although mean monthly outpatient and inpatient visits (5.0–5.6 OP visits; 0.21–0.32 IP visits) remained stable across advancing Lines of therapy(LOT), the mean all cause monthly costs (not including medication cost) were 16%—35% lower in LOT 1 ($23.6 K) compared to LOT 4($31.8 K) [ 16 ]. This may suggest that choosing the most effective regimen for the first LOT may be a cost-effective strategy and reduce the overall treatment cost by lowering inpatient and outpatient visits.

Indirect Costs

There is limited data on the indirect costs incurred by multiple myeloma patients. Most studies focus on drug costs, inpatient, and outpatient costs when reporting cost burden in multiple myeloma patients. Indirect costs like loss of income, supportive care service costs, disability claims, absenteeism, presenteeism, caregiver absenteeism, loss from early retirement and premature death etc. are often ignored underestimating the economic burden on multiple myeloma patients and the society. While direct medical costs may be easier to obtain from billing and administrative databases, estimating indirect costs involves longitudinal assessment of work-related limitations and productivity losses using standardized questionnaires and tools along with patient reported outcomes. The heterogeneity in economic burden based on patient, disease, treatment, and socioeconomic factors further complicates assessment of indirect costs.

Drug administration time needs to be considered while assessing the economic burden of treatments in multiple myeloma. Traditional chemotherapy regimens often demand significant time commitment from patients, caregivers, and healthcare workers taking up to 65 min for each administration session which is around 24—36 h per year (Table 2 ). Newer therapies like T-cell engagers would consume around 5 min per session for their administration and around 3 h per year, resulting in a substantial reduction in healthcare resource utilization and potential cost savings (Table 2 ). Table 2 Administration Time Comparison Between Commonly used Regimens and T-cell Engagers in Multiple Myeloma Regimen Drug 1 (Administration time per session) Drug 2 (Administration time per session) Drug 3 (Administration time per session) Total Estimated Administration Time Per Session (Minutes) Total Estimated Annual Administration Time Per Patient (Hours) DKD Daratumumab Subcutaneous (3–5 min) Carfilzomib (30 min) Dexamethasone with premeds (30 min) 65 24 KPD Carfilzomib 30 min Pomalyst (0 Minutes) Dexamethasone with premeds (30 min) 60 36 Teclistamab* Teclistmab (5 min) N/A N/A 5 3 Elrantamab* Elrantamab (5 min) N/A N/A 5 3 * = No premedications required; assumes patients have completed step-up dosing; Administration times are estimates based on standard treatment protocols and may vary based on individual patient responses and clinical practice settings

Table 2
Administration Time Comparison Between Commonly used Regimens and T-cell Engagers in Multiple Myeloma
* = No premedications required; assumes patients have completed step-up dosing; Administration times are estimates based on standard treatment protocols and may vary based on individual patient responses and clinical practice settings

RegimenDrug 1 (Administration time per session)Drug 2 (Administration time per session)Drug 3 (Administration time per session)Total Estimated Administration Time Per Session (Minutes)Total Estimated Annual Administration Time Per Patient (Hours)
DKDDaratumumab Subcutaneous (3–5 min)Carfilzomib (30 min)Dexamethasone with premeds (30 min)6524
KPDCarfilzomib 30 minPomalyst (0 Minutes)Dexamethasone with premeds (30 min)6036
Teclistamab*Teclistmab (5 min)N/AN/A53
Elrantamab*Elrantamab (5 min)N/AN/A53

Robinson et al. in an analysis based on ‘a” multicenter randomized control study of 263 relapsed refractory multiple myeloma (RRMM) patients reported that only 10.8% of patients aged ≤ 65 years were working and 37% of those working reported absenteeism of ≥ 1 day over last 4 weeks. The study also noted that 48% of the patients not working attributed it to their RRMM [ 17 ]. Merola et al. analyzed around 300 newly diagnosed multiple myeloma patients on oral vs injectable chemotherapy regimens and reported that patients on oral regimens had fewer days of absenteeism (83 vs 110 days) and lower costs incurred from productivity loss ($14,429 vs $18,315) over 1 year period [ 18 ]. Another European based cross-sectional study of 115 newly diagnosed multiple myeloma (NDMM) patients undergoing ASCT suggested of 76.5% of the total cohort that were productive before ASCT, only 39.1% were able to maintain productive life post ASCT and average per patient productivity loss over 20-year horizon to be around 290,601 euros [ 19 ]. In an analysis on multiple myeloma patients from Portugal, Miguel et al. suggested that indirect costs account to 18% of total cost burden with early retirement being the major driver of this cost and caregiver’s work absence being the least affecting factor [ 20 ].

Hence therapies which can 1. Minimize indirect costs to patients 2. Which will continue leading a productive life as desired by patients should also be taken account of in cost analysis.

Methodologies for Conducting Cost-Effectiveness Analyses in Healthcare

As discussed, the morbidity and mortality of multiple myeloma patients has substantially increased with newer therapies. The cost burden is also significantly raised with these novel therapies which can be related to direct costs, indirect costs, or treatment related adverse effects management costs. Cost-effectiveness analyses are essential for policy makers and clinicians to make informed decisions on the use of these novel therapies like CAR-T therapy and bispecific antibodies for multiple myeloma patients. Cost-effectiveness analysis looks to see if the treatment being analyzed offers health gains relative to its cost. In cost–benefit analysis both costs incurred, and benefits gained are measured in monetary terms for direct comparison. Most cost-effectiveness studies calculate the incremental cost-effectiveness ratio (ICER) which measures the cost per additional year of life gained with the treatment. This is then compared against the willingness to pay (WTP) threshold for the country to determine cost effectiveness of the treatment. Alternatively, studies may report incremental net benefit (INB) which incorporates the willingness to pay and thus a positive INB is considered cost-effective, which is the difference between calculated cost patients are willing to pay for the additional health gain and the actual additional costs with the treatment for the health gains. Multiple pharmacoeconomic models have been used for cost-effective analysis including the Markov model, decision trees, and Monte Carlo model. When estimating cost-effectiveness in patients with multiple myeloma, the Markov model helps researchers estimate the outcomes in terms of how different patients may transition to remission, progression, hospitalization, needing the next line of treatment etc. and hence calculate the associated costs. Decision tree model is a visual representation of outcome probabilities based on treatment options selected after considering the efficacy and adverse effects. As compared to Markov model, it may be simpler to interpret and understand but is typically a short-term analysis and does not include the comprehensive and dynamic effects of treatment on disease state. Monte Carlo method is a more robust computational model that incorporates parameters like response rates, adverse effects, and healthcare costs to run multiple random samples with distribution of these parameters and hence generate the likelihood of outcomes to further estimate the probability of the treatment being cost effective as compared to willingness to pay thresholds. Monte Carlo method incorporates and handles uncertainty by randomly selecting values from probability distribution of the input parameters. It can also predict long term outcomes over multiple time periods like the Markov model [ 21 – 24 ].

Review of Published Cost-Effectiveness Studies Evaluating CAR-T in Multiple Myeloma

Yamamoto et al. used the Markov and Monte Carlo analysis model on data from LocoMMotion, KarMMa, and CARTITUDE-1 trials to compare the cost-effectiveness of anti BCMA CAR-T [idecabtagene vicleucel(ide-cel) or ciltacabtagene autoleucel(cilta-cel)] for triple class exposed RRMM patients vs no CAR-T (multiagent chemotherapy) strategy over 5 and 10 year timeline in patients in Japan and USA. The analysis included various uncertainties regarding long-term PFS with CAR-T therapy. The study suggested that over a 10-year time horizon CAR-T therapy with cilta-cel may be cost-effective in the USA under a modest PFS of 30% but not ide-cel. The study also noted that BCMA CAR-T therapy was not found to be cost-effective even at the most optimistic PFS over a shorter, 3-year time horizon [ 25 ]. Another system-based study by Wu et al. using the Monte Carlo method analyzed the same trials as Yamamoto et al. but MAMMOTH trial instead of LocoMMotion, reported the probability of being cost-effective as 0% and 72% respectively for ide-cel and cilta-cel therapies based on the WTP thresholds established in China [ 26 ].

Kapinos et al. analyzed data from DREAMM 2, KarMMa, and CARTITUDE-1 trial using Monte Carlo Markov Chain microsimulation model and estimated that CAR-T therapy in triple refractory MM patients although was 6 times more expensive resulted in 6–8 times greater QALYs (Quality Adjusted Life Years) gained, with cilta-cel having better ICER than ide-cel [ 27 ]. The ICER ($123,618) reported by Kapinos et al. was lower than that reported ($253,000) by the Institute for Clinical and Economic Review [ 28 ]. The difference could have arisen because Kapinos et al. calculated adverse effects differently and adjusted separately for cytokine release syndrome (CRS) and neurotoxicity. The study did not include indirect costs. The ICER calculated by Kapinos et al. is in comparison to Belantamab as opposed to comparison with a market basket in the study by Institute for Clinical and Economic Review. In Fig. 1 we summarize the Quality-Adjusted Life Years (QALY) Gained for Various Treatments in Multiple Myeloma. Fig. 1 Cost and Quality-Adjusted Life Years (QALY) Gained for Various Treatments in Multiple Myeloma: Comparisons Across Studies. Cilta-cel: Ciltacabtagene autoleucel, Ide-cel: Idecabtagene vicleucel, Standard Chemotherapy: Standard chemotherapy regimens as defined in the respective studies, Belantamab: Belantamab mafodotin, QALY gained: Quality adjusted life years gained

Fig. 1 Cost and Quality-Adjusted Life Years (QALY) Gained for Various Treatments in Multiple Myeloma: Comparisons Across Studies. Cilta-cel: Ciltacabtagene autoleucel, Ide-cel: Id…
Fig. 1 Cost and Quality-Adjusted Life Years (QALY) Gained for Various Treatments in Multiple Myeloma: Comparisons Across Studies. Cilta-cel: Ciltacabtagene autoleucel, Ide-cel: Idecabtagene vicleucel, Standard Chemotherapy: Standard chemotherapy regimens as defined in the respective studies, Belantamab: Belantamab mafodotin, QALY gained: Quality adjusted life years gained

Challenges and Considerations of Cost Effectiveness of CAR-T Therapy

Overall, the cost-effectiveness of CAR-T therapy in RRMM patients varied based on the drug used (ide-cel vs cilta-cel), PFS data, geographical area, whether indirect costs are considered, comparator used, and methodologic factors like adjusting for adverse effects and sensitivity analysis used. Cost-effectiveness varied based on long term survival with CAR-T therapy. If patients are treatment free during remission this could substantially decrease treatment costs and hence improve cost-effectiveness. Data for cost-effectiveness for CAR-T was based on initial single arm studies, data from randomized control trials (RCTs) and long term follow-up is lacking. Yamamoto et al. suggested that CAR-T may be cost-effective if data from KarMMa-2 or CARTITUDE-2 trial was used as this may result in longer PFS and treatment free intervals given patients with fewer lines of prior treatment in this trial. Studies have suggested that cilta-cel is more cost-effective than ide-cel but it should also be noted that the KarMMa trial for ide-cel although mostly similar population to the CARTITUDE-1 trial for cilta-cel, had more patients with extramedullary disease and high-risk cytogenetics which may be markers of severe disease. Unlike for other hematologic malignancies, CAR-T therapy is not considered curative for MM and virtually all patients progress which affects the cost-effectiveness [ 29 ]. Further research in CAR-T therapies addressing antigen escape, trogocytosis, depletion of CAR-T cells, and immune suppression by tumor microenvironment which are implicated as challenges to CAR-T therapy in MM patients can improve outcomes with CAR-T therapy and hence its cost-effectiveness [ 8 , 30 – 33 ]. Future studies will be needed to see if the heightened costs of treatment with these novel therapies have an impact on minimizing productivity losses and other indirect costs. Most studies also do not account for indirect costs like transportation, delay for product delivery etc. which can be considered by future studies. In Table 2 we compare the administration time between commonly used regimens and T-cell Engagers in Multiple Myeloma. With the high costs of CAR-T and other newer therapies, sustainability of healthcare systems as in the ability of healthcare systems in delivering expensive treatments to a predominantly older population which at least in the US is majorly publicly insured is an important factor to consider. The increasing financial burden on public insurance programs could strain the ability to provide widespread access to these advanced therapies. Policy changes at federal and state levels are needed to negotiate with drug manufacturers and insurers are needed to bring down costs. Other approaches to include is optimal dosing – moving from once weekly to twice weekly or monthly with equal efficacy outcomes, time limited therapy and avoiding combination therapy unless there is a clearly proven benefit are necessary are some strategies to decrease cost. Further research on cost-effectiveness of different MM regimens will help healthcare providers to find the optimal treatment pathway minimizing costs for both payers and patients.

Cost-Effectiveness of Bispecific antibodies in Multiple Myeloma Patients

Bispecific antibodies have emerged as promising therapies for triple class refractory multiple myeloma patients based on early phase clinical trials [ 34 ]. Bispecific antibodies developed for multiple myeloma currently target B-cell maturation antigen (BCMA), G protein–coupled receptor, class C, group 5, member D (GPRC5D), Fc receptor-like 5 (FcRL5), or CD-38. A recent meta-analysis of prospective clinical trials on 1473 RRMM patients reported an overall pooled ORR of 61% with 28% and 33% of patients achieving complete response in the BCMA and non BCMA bispecific antibody treatment groups respectively. The study also reported any grade neutropenia (48% vs 18%), lymphopenia (38% vs 8%), CRS (64% vs 66%), infections (47% vs 49%), immune effector cell-associated neurotoxicity syndrome(ICANS)(11% vs 2%) as major adverse effects in BCMA and non BCMA groups respectively (35). Currently there are no cost effectiveness studies for bispecific antibodies in multiple myeloma patients likely due to lack of long-term clinical data. The improved efficacy shown in clinical trials may translate into cost-effectiveness, but this should be weighed against the high costs of the drug therapy along with costs involved in potential adverse effect management. Although bispecific antibody therapy is less toxic compared to CAR-T therapy including lower high grade CRS events, it is an ongoing therapy unlike CAR-T which is one time session. Multiple sessions may account for higher costs compared to CAR-T therapy. Bispecific antibody therapy would not incur additional costs from delay in initiation due to production which is an issue with CAR-T therapy. The drug costs may decrease in the future with expansion in the market, increase in bispecific antibody options, limited duration of therapy and use for patients early in the disease spectrum. Future studies investigating the cost-effectiveness of different bispecific antibodies and possible head-to-head comparison to CAR-T therapy will be needed to understand the best options further.

Conclusions

In conclusion, in this article we review the cost effectiveness of various treatments including CAR-T and Bispecific antibodies. Effective drugs in earlier LOT are more cost effective over the course of time than in later LOT due to longer PFS. CAR-T used in earlier LOT and combined with a longer PFS are likely to be cost effective depending on the country and the model used. Further research is needed for bispecific antibodies and their cost effectiveness in multiple myeloma.

Key References

Yamamoto C, Minakata D, Yokoyama D, et al. Cost-effectiveness of anti-bcma chimeric antigen receptor t cell therapy in relapsed/refractory multiple myeloma. Transplant Cell Ther. 2024;30(1):118.e1-118.e15. This study compared the effectiveness of anti BCMA CART to the LOCOMOTION trial. 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. This study compared the QALY of CART when compared to other third line therapies in myeloma Robinson D, Orlowski RZ, Stokes M, et al. Economic burden of relapsed or refractory multiple myeloma: Results from an international trial. Eur J Haematol. 2017;99(2):119–132. This study shows the indirect costs for patients with myeloma.

Publisher's Note

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Author Contributions

Concept and design: PRK, MJ.

Drafting of the manuscript: PRK, DS, CTRV, YSP, RK, MD, MJ.

Tables and Figures: PRK, DS, MJ.

Critical revision of the manuscript for important intellectual content: PRK, DS, CTRV, YSP, RK, MD, MJ.

Funding

Open access funding provided by SCELC, Statewide California Electronic Library Consortium

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Conflict of Interest

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Disclosure

None.

References

1. American Cancer Society. Key Statistics About Multiple Myeloma. American Cancer Society website. https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statis-tics.html . Published 2023. Accessed July 12, 2024.

2. Ludwig H Bolejack V Crowley J Survival and years of life lost in different age cohorts of patients with multiple myeloma J Clin Oncol 2010 28 9 1599 1605 10.1200/JCO.2009.25.2114 20177027 Ludwig H, Bolejack V, Crowley J, et al. Survival and years of life lost in different age cohorts of patients with multiple myeloma. J Clin Oncol. 2010;28(9):1599–605. 20177027 10.1200/JCO.2009.25.2114

3. Yang J Boytsov N Carlson JJ Barthold D Health care resource utilization and costs among patients with multiple myeloma with exposure to double-class or triple-class multiple myeloma treatments: A retrospective US claims database analysis J Manag Care Spec Pharm 2023 29 8 917 926 37523320 10.18553/jmcp.2023.29.8.917 PMC10397331 Yang J, Boytsov N, Carlson JJ, Barthold D. Health care resource utilization and costs among patients with multiple myeloma with exposure to double-class or triple-class multiple myeloma treatments: A retrospective US claims database analysis. J Manag Care Spec Pharm. 2023;29(8):917–26. 37523320 10.18553/jmcp.2023.29.8.917 PMC10397331

4. Hollmann S Moldaver D Goyert N Grima D Maiese EM A u. S. Cost analysis of triplet regimens for patients with previously treated multiple myeloma J Manag Care Spec Pharm 2019 25 4 449 459 30917078 10.18553/jmcp.2019.25.4.449 PMC10397865 Hollmann S, Moldaver D, Goyert N, Grima D, Maiese EM. A u. S. Cost analysis of triplet regimens for patients with previously treated multiple myeloma. J Manag Care Spec Pharm. 2019;25(4):449–59. 30917078 10.18553/jmcp.2019.25.4.449 PMC10397865

5. Madduri D Hagiwara M Parikh K 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 5 503 515 10.2217/fon-2020-1003 33522834 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(5):503–15. 33522834 10.2217/fon-2020-1003

6. Jagannath S Joseph N He J Healthcare costs incurred by patients with multiple myeloma following triple class exposure (Tce) in the us Oncol Ther 2021 9 2 659 669 10.1007/s40487-021-00175-z 34694578 PMC8593112 Jagannath S, Joseph N, He J, et al. Healthcare costs incurred by patients with multiple myeloma following triple class exposure (Tce) in the us. Oncol Ther. 2021;9(2):659–69. 34694578 10.1007/s40487-021-00175-z PMC8593112

7. Noori M Yazdanpanah N Rezaei N Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis Cancer Cell Int 2023 23 1 193 10.1186/s12935-023-03045-y 37670301 PMC10478206 Noori M, Yazdanpanah N, Rezaei N. Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis. Cancer Cell Int. 2023;23(1):193. 37670301 10.1186/s12935-023-03045-y PMC10478206

8. Sheykhhasan M Ahmadieh-Yazdi A Vicidomini R CAR T therapies in multiple myeloma: unleashing the future Cancer Gene Ther 2024 31 5 667 686 10.1038/s41417-024-00750-2 38438559 PMC11101341 Sheykhhasan M, Ahmadieh-Yazdi A, Vicidomini R, et al. CAR T therapies in multiple myeloma: unleashing the future. Cancer Gene Ther. 2024;31(5):667–86. 38438559 10.1038/s41417-024-00750-2 PMC11101341

9. Rajkumar SV Value and cost of myeloma therapy Am Soc Clin Oncol Educ Book 2018 38 662 666 10.1200/EDBK_200867 30231405 Rajkumar SV. Value and cost of myeloma therapy. Am Soc Clin Oncol Educ Book. 2018;38:662–6. 30231405 10.1200/EDBK_200867

10. Bayani DB Lin YC Ooi MG Tso ACY Wee HL Real-world utilization and healthcare costs for multiple myeloma: A retrospective analysis of patients in Singapore EJHaem 2023 4 4 1013 1018 10.1002/jha2.798 38024607 PMC10660121 Bayani DB, Lin YC, Ooi MG, Tso ACY, Wee HL. Real-world utilization and healthcare costs for multiple myeloma: A retrospective analysis of patients in Singapore. EJHaem. 2023;4(4):1013–8. 38024607 10.1002/jha2.798 PMC10660121

11 Ashcroft J Judge D Dhanasiri S Taylor-Stokes G Middleton C Chart review across EU5 in MM post-ASCT patients Int J Hematol Oncol 2018 7 1 IJH05 10.2217/ijh-2018-0004 30302236 PMC6176952 Ashcroft J, Judge D, Dhanasiri S, Taylor-Stokes G, Middleton C. Chart review across EU5 in MM post-ASCT patients. Int J Hematol Oncol. 2018;7(1):IJH05. 30302236 10.2217/ijh-2018-0004 PMC6176952

12. Gonzalez-McQuire S Yong K Leleu H Healthcare resource utilization among patients with relapsed multiple myeloma in the UK, France, and Italy J Med Econ 2018 21 5 450 467 10.1080/13696998.2017.1421546 29278014 Gonzalez-McQuire S, Yong K, Leleu H, et al. Healthcare resource utilization among patients with relapsed multiple myeloma in the UK, France, and Italy. J Med Econ. 2018;21(5):450–67. 29278014 10.1080/13696998.2017.1421546

13. Choon-Quinones M Zelei T Barnett M Beyond medicines’ barriers: exploring the true cost of multiple myeloma J Med Econ 2022 25 1 1167 1175 10.1080/13696998.2022.2133823 36397678 Choon-Quinones M, Zelei T, Barnett M, et al. Beyond medicines’ barriers: exploring the true cost of multiple myeloma. J Med Econ. 2022;25(1):1167–75. 36397678 10.1080/13696998.2022.2133823

14. Touati M Lamarsalle L Moreau S Cost savings of home bortezomib injection in patients with multiple myeloma treated by a combination care in Outpatient Hospital and Hospital care at Home Support Care Cancer 2016 24 12 5007 5014 27525991 10.1007/s00520-016-3363-3 PMC5082582 Touati M, Lamarsalle L, Moreau S, et al. Cost savings of home bortezomib injection in patients with multiple myeloma treated by a combination care in Outpatient Hospital and Hospital care at Home. Support Care Cancer. 2016;24(12):5007–14. 27525991 10.1007/s00520-016-3363-3 PMC5082582

15 Gupta N Tai MH Kaila S Real-world healthcare resource utilization and costs among patients with multiple myeloma in the United States JCO 2022 40 16_suppl e18811 e18811 10.1200/JCO.2022.40.16_suppl.e18811 Gupta N, Tai MH, Kaila S, et al. Real-world healthcare resource utilization and costs among patients with multiple myeloma in the United States. JCO. 2022;40(16_suppl):e18811–e18811.

16. Robinson D Orlowski RZ Stokes M Economic burden of relapsed or refractory multiple myeloma: Results from an international trial Eur J Haematol 2017 99 2 119 132 10.1111/ejh.12876 28306169 Robinson D, Orlowski RZ, Stokes M, et al. Economic burden of relapsed or refractory multiple myeloma: Results from an international trial. Eur J Haematol. 2017;99(2):119–32. 28306169 10.1111/ejh.12876

17. Merola D Yong C Noga SJ Shermock KM Costs associated with productivity loss among u. S. Patients newly diagnosed with multiple myeloma receiving oral versus injectable chemotherapy J Manag Care Spec Pharm 2018 24 10 1019 1026 30247101 10.18553/jmcp.2018.24.10.1019 PMC10397991 Merola D, Yong C, Noga SJ, Shermock KM. Costs associated with productivity loss among u. S. Patients newly diagnosed with multiple myeloma receiving oral versus injectable chemotherapy. J Manag Care Spec Pharm. 2018;24(10):1019–26. 30247101 10.18553/jmcp.2018.24.10.1019 PMC10397991

18. Jackson G Galinsky J Alderson DEC Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy Eur J Haematol 2019 103 4 393 401 10.1111/ejh.13298 31325331 PMC6899492 Jackson G, Galinsky J, Alderson DEC, et al. Productivity losses in patients with newly diagnosed multiple myeloma following stem cell transplantation and the impact of maintenance therapy. Eur J Haematol. 2019;103(4):393–401. 31325331 10.1111/ejh.13298 PMC6899492

19. Miguel S Pedrosa H Carrilho M Ee287 indirect costs of multiple myeloma in portugal Value in Health 2022 25 12 S110 10.1016/j.jval.2022.09.534 Miguel S, Pedrosa H, Carrilho M, et al. Ee287 indirect costs of multiple myeloma in portugal. Value in Health. 2022;25(12):S110.

20. Carta A Conversano C On the use of markov models in pharmacoeconomics: pros and cons and implications for policy makers Front Public Health 2020 8 569500 10.3389/fpubh.2020.569500 33194969 PMC7661756 Carta A, Conversano C. On the use of markov models in pharmacoeconomics: pros and cons and implications for policy makers. Front Public Health. 2020;8:569500. 33194969 10.3389/fpubh.2020.569500 PMC7661756

21. del Campo C Bai J Keller LR Comparing Markov and non-Markov alternatives for cost-effectiveness analysis: Insights from a cervical cancer case Oper Res Health Care 2019 21 32 43 10.1016/j.orhc.2019.04.001 del Campo C, Bai J, Keller LR. Comparing Markov and non-Markov alternatives for cost-effectiveness analysis: Insights from a cervical cancer case. Oper Res Health Care. 2019;21:32–43.

22. Guggenbickler AM Barr HK Hoch JS Dewa CS Rapid review of real-world cost-effectiveness analyses of cancer interventions in canada Curr Oncol 2022 29 10 7285 7304 10.3390/curroncol29100574 36290851 PMC9600856 Guggenbickler AM, Barr HK, Hoch JS, Dewa CS. Rapid review of real-world cost-effectiveness analyses of cancer interventions in canada. Curr Oncol. 2022;29(10):7285–304. 36290851 10.3390/curroncol29100574 PMC9600856

23. Barr HK Guggenbickler AM Hoch JS Dewa CS Real-world cost-effectiveness analysis: how much uncertainty is in the results? Curr Oncol 2023 30 4 4078 4093 10.3390/curroncol30040310 37185423 PMC10136635 Barr HK, Guggenbickler AM, Hoch JS, Dewa CS. Real-world cost-effectiveness analysis: how much uncertainty is in the results? Curr Oncol. 2023;30(4):4078–93. 37185423 10.3390/curroncol30040310 PMC10136635

24. Yamamoto C Minakata D Yokoyama D Cost-effectiveness of anti-bcma chimeric antigen receptor t cell therapy in relapsed/refractory multiple myeloma Transplant Cell Ther 2024 30 1 118.e1 118.e15 10.1016/j.jtct.2023.10.001 37802181 Yamamoto C, Minakata D, Yokoyama D, et al. Cost-effectiveness of anti-bcma chimeric antigen receptor t cell therapy in relapsed/refractory multiple myeloma. Transplant Cell Ther. 2024;30(1):118.e1-118.e15. 37802181 10.1016/j.jtct.2023.10.001

25. Wu W Ding S Mingming Z Cost effectiveness analysis of CAR-T cell therapy for patients with relapsed/refractory multiple myeloma in China J Med Econ 2023 26 1 701 709 10.1080/13696998.2023.2207742 37145966 Wu W, Ding S, Mingming Z, et al. Cost effectiveness analysis of CAR-T cell therapy for patients with relapsed/refractory multiple myeloma in China. J Med Econ. 2023;26(1):701–9. 37145966 10.1080/13696998.2023.2207742

26. 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 10732748221142944 10.1177/10732748221142945 PMC9869188 36651055 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;30:10732748221142944. 10.1177/10732748221142945 PMC9869188 36651055

27. Beinfeld M Lee S McQueen B Fluetsch N Pearson SD Ollendorf DA Anti B-cell maturation antigen CAR T-cell and antibody drug conjugate therapy for heavily pretreated relapsed and refractory multiple myeloma J Manag Care Spec Pharm 2021 27 9 1315 1320 34464215 10.18553/jmcp.2021.27.9.1315 PMC10391002 Beinfeld M, Lee S, McQueen B, Fluetsch N, Pearson SD, Ollendorf DA. Anti B-cell maturation antigen CAR T-cell and antibody drug conjugate therapy for heavily pretreated relapsed and refractory multiple myeloma. J Manag Care Spec Pharm. 2021;27(9):1315–20. 34464215 10.18553/jmcp.2021.27.9.1315 PMC10391002

28. Teoh PJ Chng WJ CAR T-cell therapy in multiple myeloma: more room for improvement Blood Cancer J 2021 11 4 84 10.1038/s41408-021-00469-5 33927192 PMC8085238 Teoh PJ, Chng WJ. CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 2021;11(4):84. 33927192 10.1038/s41408-021-00469-5 PMC8085238

29. Lee H Ahn S Maity R Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma Nat Med 2023 29 9 2295 2306 10.1038/s41591-023-02491-5 37653344 PMC10504087 Lee H, Ahn S, Maity R, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023;29(9):2295–306. 37653344 10.1038/s41591-023-02491-5 PMC10504087

30. Liu Y An L Huang R Strategies to enhance CAR-T persistence Biomark Res 2022 10 1 86 10.1186/s40364-022-00434-9 36419115 PMC9685914 Liu Y, An L, Huang R, et al. Strategies to enhance CAR-T persistence. Biomark Res. 2022;10(1):86. 36419115 10.1186/s40364-022-00434-9 PMC9685914

31. KankeuFonkoua LA Sirpilla O Sakemura R Siegler EL Kenderian SS CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities Mol Ther Oncolytics 2022 25 69 77 10.1016/j.omto.2022.03.009 35434273 PMC8980704 KankeuFonkoua LA, Sirpilla O, Sakemura R, Siegler EL, Kenderian SS. CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities. Mol Ther Oncolytics. 2022;25:69–77. 35434273 10.1016/j.omto.2022.03.009 PMC8980704

32. Camviel N Wolf B Croce G Gfeller D Zoete V Arber C Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization J Immunother Cancer 2022 10 11 e005091 10.1136/jitc-2022-005091 36323436 PMC9639149 Camviel N, Wolf B, Croce G, Gfeller D, Zoete V, Arber C. Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. J Immunother Cancer. 2022;10(11):e005091. 36323436 10.1136/jitc-2022-005091 PMC9639149

33. Ravi G Costa LJ Bispecific T-cell engagers for treatment of multiple myeloma Am J Hematol 2023 98 Suppl 2 S13 S21 35702871 10.1002/ajh.26628 Ravi G, Costa LJ. Bispecific T-cell engagers for treatment of multiple myeloma. Am J Hematol. 2023;98(Suppl 2):S13–21. 35702871 10.1002/ajh.26628

34. Wang X Zhao A Zhu J Niu T Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials Front Immunol 2024 15 1348955 10.3389/fimmu.2024.1348955 38482019 PMC10933024 Wang X, Zhao A, Zhu J, Niu T. Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials. Front Immunol. 2024;15:1348955. 38482019 10.3389/fimmu.2024.1348955 PMC10933024

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты