Mosunetuzumab in relapsed or refractory follicular lymphoma: a budget impact analysis in real-world clinical practice

Introduction

Follicular lymphoma (FL) is a malignant B‑cell neoplasm that arises from germinal center cells — centrocytes and centroblasts. Morphologically, the disease is in most cases characterized by a follicular growth pattern, reflecting its origin and biological features [1, 2].

FL is traditionally classified as an indolent form of non‑Hodgkin lymphoma; however, its clinical course is heterogeneous. Some patients experience long periods of remission and relatively slow progression, while in others the disease acquires aggressive features and is associated with a poor prognosis: mortality within the first five years after diagnosis can reach 50% [3, 4].

A key feature of FL is its chronic, relapsing course. As the disease progresses, treatment efficacy declines and the range of available therapeutic options narrows. An analysis of real‑world clinical practice in Russia shows a marked decrease in the number of patients moving to each subsequent line of treatment [5]. While more than 90% of newly diagnosed patients receive first‑line therapy, only about 17% of the entire patient population reaches third and subsequent lines [6].

This cohort represents the greatest clinical and organizational challenge. In the 3rd and later lines, the complete response rate does not exceed 20%, and median progression‑free survival is about 10 months. Standard immunochemotherapy regimens have generally exhausted their potential by this stage, and cumulative toxicity limits further treatment options. Thus, patients with relapsed or refractory FL belong to a group with a high level of unmet medical need [1, 2, 7, 8].

In recent years, the therapeutic arsenal has expanded with the introduction of immunological approaches, including bispecific antibodies. One such drug is mosunetuzumab — a humanized full‑length bispecific monoclonal antibody of the IgG1 class that can simultaneously bind CD20 on the surface of B‑cells and CD3 on T‑lymphocytes. This mechanism results in directed activation of T‑cell cytotoxic responses and elimination of malignant B‑cells [9–11].

In Russia, mosunetuzumab is registered for use as monotherapy in adult patients with relapsed or refractory FL after at least two lines of systemic therapy. The dosing regimen involves stepwise dose escalation in the first cycles, followed by fixed doses; the cycle length is 21 days, and total treatment duration is limited to 8 cycles when complete response is achieved, or may be extended to 17 cycles if complete response is not achieved after cycle 8 [9–11].

The clinical efficacy of the drug was demonstrated in the multicenter phase II study GO29781 [12], which included patients with heavily pretreated disease, including cases of double refractoriness and early progression (POD24). Overall response and complete response rates reached 80% (95% confidence interval (CI) 70.3–87.8) and 60% (95% CI 49.1–70.1), respectively. Median progression‑free survival was 24 months, and a high rate of durable responses was maintained with long‑term follow‑up [12, 13]. Thus, fixed‑duration therapy with mosunetuzumab achieves meaningful clinical outcomes in pretreated patients with relapsed or refractory FL [14].

At the same time, given the resource constraints of the Russian healthcare system, assessing the financial consequences of implementing this technology into practice remains important. We have previously published the results of a budget impact analysis (BIA) of mosunetuzumab in patients with relapsed or refractory FL in the 3rd and subsequent lines of therapy [15]. Our approach to estimating current practice costs was based on real‑world clinical practice data from the work of Poddubnaya I.V. and Babicheva L.G., 2024 [16], which used online questionnaire data from 130 medical specialists from 30 regions of the Russian Federation conducted in 2023. On further monitoring of the Russian literature on this topic, we found a publication by Smolyaninova A.K. et al., 2025 [17], which presents the results of a retrospective cohort analysis of the telemedicine consultation database of the National Medical Research Center of Hematology for the period 2019 – July 2025, including 311 FL patients from 71 cities in 27 constituent entities of the Russian Federation. Given the cost estimation approach based on real‑world clinical practice and the variations in treatment approaches for patients with relapsed or refractory FL in the 3rd and subsequent lines between the identified publications, it is of interest to conduct an updated analysis and compare the results.

Objective of this study — to assess the budget impact on the Russian healthcare system of the use of mosunetuzumab in adult patients with relapsed or refractory FL who have previously received at least two lines of systemic therapy, taking into account updated real‑world clinical practice data.

Materials and methods

Design: budget impact analysis (BIA) and univariate deterministic sensitivity analysis (SA) in accordance with the recommendations of the Federal State Budgetary Institution “Center for Expertise and Quality Control of Medical Care” (CEQCMC) of the Ministry of Health of Russia [18, 19].

Study hypothesis: Regardless of the current practice considered, the use of mosunetuzumab in patients with relapsed or refractory FL is an economically feasible option for 3rd and subsequent line therapy in adult patients within the Russian healthcare system.

Target population: 340 adult patients over 18 years of age with relapsed or refractory FL who have previously received at least two lines of systemic therapy.

Study perspective: Russian healthcare system.

Time horizon: 1 year.

Technology under study: mosunetuzumab (Lunsumio), concentrate for solution for infusion 1 mg or 30 mg (F. Hoffmann‑La Roche Ltd, Switzerland) [13].

Comparator technologies: Treatments used for patients receiving 3rd and subsequent lines of therapy in real‑world clinical practice [17]: R‑CHOP, G‑CHOP, G‑CVP, RB, GB, GB‑Lena, R‑BAC, R‑ICE, G‑ICE, R‑DHAP, G‑DHAP, R‑GEMOX, G‑GEMOX, R‑IGEV, R2, G‑Lena, Lena, RB‑Lena, R‑Ibr‑Lena, DHAP, ESHAP, GDP, GIDOX, bendamustine, FCM, CVP, BeGEV, Nivo‑BeGEV, G‑VIPOR, Beam+Lena, R‑FMC, Pola‑BR, brentuximab vedotin, ibrutinib, glofitamab, ChLVPP, PEPC, rituximab monotherapy (R), mNHL — BFM‑90, and autologous hematopoietic stem cell transplantation (auto‑HSCT).

Direct medical costs considered:

1. drug therapy costs;

2. costs of performing auto‑HSCT.

Budget impact analysis methodology. Since BIA is part of a comprehensive evaluation of medicinal products and aims to assess the financial consequences of their use [18], this study evaluated the economic consequences of including mosunetuzumab in the List of Vital and Essential Drugs (VED) within the framework of the State Guarantees Program (SGP).

Two alternative scenarios for the treatment of patients with relapsed or refractory FL were considered:

• Current medical practice (based on real‑world clinical practice data) — baseline, describes current expenditures on 3rd and subsequent line therapy;

• Simulated medical practice (taking into account the predicted change in the drug supply structure for patients) — alternative, describes the predicted change in expenditures of the Russian healthcare system when mosunetuzumab is included in the VED list.

The estimated size of the target population for the BIA in our study is 340 patients with relapsed or refractory FL; the method for determining the size was described previously [15].

To characterize the therapy structure of the target patient population in current practice, we used the results of a retrospective cohort analysis of the telemedicine consultation database of the National Medical Research Center of Hematology for the period 2019 – July 2025. The study included 311 FL patients from 71 cities in 27 constituent entities of the Russian Federation, of which 65% had relapsed or refractory disease [17].

Since this BIA considered aggregated data for the 3rd and subsequent lines of therapy, an in‑depth evaluation of all therapy options and patient distribution across lines 3‑8 was carried out jointly with experts in oncohematology.

Initially, all therapy options actually used in real‑world clinical practice were included in the analysis. This was due to the high variability of treatment approaches starting from the 3rd line and the lack of a unified strategy for managing patients after the second relapse. According to an expert survey, the key difficulties of treatment in this population are: low probability of achieving complete response (68% of respondents), high proportion of patients with poor prognosis (60% of respondents), limited efficacy of existing options (51% of respondents), and cumulative toxicity of prior therapy (50% of respondents) [16, 20].

Among the analyzed therapy options in real‑world clinical practice, the following were present:

• drug therapy regimens included in current clinical guidelines and having a registered indication;

• regimens used based on clinical trial data but without an official indication for use in this patient group (off‑label);

• CAR‑T therapy;

• auto‑HSCT;

• individual drugs from the PI3K inhibitor group not currently registered in the Russian Federation.

Given the data collection period (2019–2025), the use of certain PI3K inhibitor drugs reflected historical practice. In the current practice model, these options were excluded from calculations.

Regarding CAR‑T therapy, an assumption was made not to include this option in the current practice calculations due to limited information on the use of this type of medical care within the SGP.

Due to the high proportion of off‑label prescriptions, a methodological assumption was made: all drug regimens for which literature search revealed data confirming clinical efficacy and safety in relapsed or refractory FL were included in the analysis.

Patients who had already been prescribed mosunetuzumab monotherapy in real practice were not considered in the structure of the current scenario for the purposes of this analysis.

After excluding irrelevant regimens, the proportions of prescriptions were recalculated, determining for each regimen the average frequency of its use in the 3rd and subsequent lines of therapy for relapsed or refractory FL.

For the simulated practice with inclusion of mosunetuzumab in the VED list, a scenario was considered in which patients receiving off‑label regimens (n=217) are switched to therapy approved for use in the 3rd and subsequent lines of treatment for relapsed or refractory FL according to current clinical guidelines from 2024 [1]. The largest proportion of patients (25 patients) in the simulated scenario were switched to mosunetuzumab monotherapy as a drug with a registered indication in adult patients after ≥2 lines of systemic therapy and a modern mechanism of action. The remaining 192 patients were evenly distributed among the other selected regimens: R‑CHOP, G‑CHOP, G‑CVP, RB, GB, R‑ICE, R‑DHAP, R‑GEMOX, R2, rituximab monotherapy, and auto‑HSCT.

To assess the budget impact of including mosunetuzumab in the VED list, the difference in direct medical costs for providing medical care to the target population of patients with relapsed or refractory FL was determined.

BIA was calculated using the formula [18]:

BIA = S(1) − S(2), where
BIA is the budget impact result (rub.);
S(1) is the total cost for the cohort of patients with relapsed or refractory FL receiving treatment in real‑world clinical practice, rub.;
S(2) is the total cost for the cohort of patients with FL receiving treatment with the proposed drug, rub.

Cost analysis methodology. Costs for all comparator technologies were estimated over one year. Dosing regimens for drugs were determined based on the official instructions for medical use [21], according to the latest Russian guidelines [1, 22], and clinical trial data [23–74].

For each drug regimen, the required amount of drug per administration, frequency of use per cycle, and number of cycles per year were determined. When calculating the number of cycles per year (365 days, 52 weeks), if no specific number of cycles was indicated, the calculation was performed taking into account the duration of one cycle. The calculation of the required amount of drug per administration assumed that the body weight of an adult is 74.46 kg and body surface area is 1.84 m² [75].

For some of the considered regimens, maintenance therapy was provided for one year after the main course of therapy if indicated in the regimen description. The frequency of maintenance therapy was determined based on aggregated real‑world clinical practice data and clinical trial data (Table 1).

Table 1. General information about regimens for which maintenance therapy was provided

For all drugs included in the VED list, prices registered in the State Register of Maximum Retail Prices [76] as of November 2025 were analyzed, including value added tax (VAT) of 10%. Where several trade names existed under the same international nonproprietary name, the average cost per 1 mg of active ingredient, taking into account the dosage form, was determined.

For the drug glofitamab, which is not included in the VED list, the cost was determined as the average cost of 2.5 mg and 10 mg of concentrate for solution for infusion based on tender procurement results according to the unified information system in the field of procurement for 2025 (as of December 17, 2025), which was 44,986.72 rubles per 2.5 mg and 44,879.40 rubles per 10 mg. The price of mosunetuzumab (Lunsumio) was provided by the marketing authorization holder (excluding VAT) per package:

• concentrate for solution for infusion, 1 mg, 1 ml — 18,323.00 rubles;

• concentrate for solution for infusion, 30 mg, 30 ml — 549,700.00 rubles.

To determine the costs of auto‑HSCT, the standards of financial costs per unit of high‑tech medical care (HTMC) according to the SGP for 2025 were analyzed [77]; thus, taking into account the ICD‑10 code (C82) for FL and the type of HTMC (autologous bone marrow transplantation), the standard value was 2,930,645.00 rubles. No other types of costs were considered within the auto‑HSCT.

Sensitivity analysis methodology. At the final stage, a univariate deterministic SA was performed to assess the robustness of the obtained results to variations in input parameters. The methodology involved sequentially changing key variables (cost of drugs, target population size, proportions of therapy regimens) by ±10% of the baseline values. Results were considered robust if the direction of the conclusion regarding the BIA hypothesis (confirmation or refutation) was maintained across the entire range of specified deviations [18].

Results

Cost analysis. Direct comparison of costs for 3rd and subsequent line therapy per patient over 1 year showed high variability (Table 2).

Table 2. Results of cost analysis for 3rd and subsequent lines of therapy over 1 year

Note: BisAT – bispecific antibody; CT – chemotherapy.

Budget impact analysis. Detailed results of the cost analysis for current practice of providing medical care to patients with relapsed or refractory FL are presented in Table 3. Total costs for 1 year amounted to 798.2 million rubles. More than 75% of costs in current practice are spent on drugs that do not have an official indication for use in patients with relapsed or refractory FL in the 3rd and subsequent lines of therapy according to the instructions for medical use and the latest Russian clinical guidelines [1].

Modeling with redistribution of patients who received off‑label regimens in current practice (217 patients) to mosunetuzumab and the following treatment approaches: R‑CHOP, G‑CHOP, G‑CVP, RB, GB, R‑ICE, R‑DHAP, R‑GEMOX, R2, auto‑HSCT and R — showed that using effective and approved regimens, treatment costs would amount to 599.1 million rubles.

Table 3. Results of cost analysis for current and simulated practices for managing patients with relapsed or refractory follicular lymphoma (n=340 patients)

Table 4. Budget Impact Analysis Results

Thus, the BIA demonstrated that the use of mosunetuzumab in the 3rd and subsequent lines of therapy for patients with relapsed or refractory FL in the Russian healthcare system, regardless of the approach to estimating current clinical practice costs, would lead to savings in the Russian healthcare budget, in this case by 24.9% over 1 year (Table 4). This would allow an additional 32 new patients to receive mosunetuzumab therapy within 1 year.

Sensitivity analysis. SA to changes in the target population size demonstrated the robustness of the developed model. When the target population size was increased by 10% to 374 patients, cost savings would be 26.6%. When the target population size was decreased by 10% to 306 patients, cost savings would be 23.5%. Regarding changes in the proportion of mosunetuzumab use, it was shown that a loss of savings compared to current practice (cost increase of 0.1% or 530,492.85 rubles) occurs when 67 patients are switched to mosunetuzumab monotherapy.

SA also revealed that when the cost of all analyzed drugs was changed either upward or downward by 10% from the initial value, the model remained robust, demonstrating budget savings over 1 year ranging from 22.8% to 26.9%. The highest level of savings (26.9%) was observed when the cost of mosunetuzumab was reduced by 10%. With the patient distribution in the simulated scenario unchanged, savings compared to current practice are maintained even when the cost of mosunetuzumab is doubled.

Discussion

The work by Smolyaninova A.K., Plastinina L.V. et al., 2025 [17], used in this analysis, confirmed our previously developed approach to estimating current practice for managing patients with relapsed or refractory FL based on real‑world clinical practice data, demonstrating unsatisfactory results of standard treatment for patients with this nosology. With each subsequent line of therapy, physicians increasingly choose non‑programmed courses, therapy with bispecific antibodies, or CAR‑T therapy. The rate and duration of overall response, as well as overall survival, substantially decrease with each relapse of FL, indicating the need for broader adoption of modern treatment methods [17].

Comparison of the prescription structure in current clinical practice as presented in the previous publication [15] and the updated model demonstrates significant changes in the distribution of therapeutic approaches in FL patients in the 3rd and subsequent lines of therapy. While the earlier analysis reflected a more limited list of regimens with a predominance of certain expensive regimens, the updated version, based on an expanded real‑world clinical practice database (2019–2025), revealed significantly greater variability in prescriptions, including a wide range of immunochemotherapy combinations, bispecific antibodies, and CAR‑T approaches, as well as a notable proportion of off‑label regimens. At the same time, it is worth noting the comparability of the obtained figures regarding current practice costs — we previously obtained costs of 891.4 million rubles [15], while the updated calculation model gave costs of 798.2 million rubles. This is due to a more detailed analysis of the prescribed regimens, among which there are many aggressive chemotherapy approaches associated with low annual cost but also low clinical efficacy and significant toxicity.

Despite the relatively high cost of mosunetuzumab monotherapy, the updated BIA confirms that its introduction into clinical practice in Russia is accompanied by a reduction in overall healthcare costs, in this case by 24.9% over one year. This is due to several factors. First, the exclusion of expensive drugs without official indications from treatment regimens, and also due to a more effective structure of patient treatment — switching from aggressive chemotherapy approaches to more effective options such as mosunetuzumab monotherapy, auto‑HSCT, etc.

There are relatively few Russian studies evaluating various pharmacoeconomic aspects of therapy for patients with relapsed or refractory FL; at the same time, new works are emerging showing the importance of developing approaches to optimize therapeutic strategies for managing this group of patients [16, 17]. As we can see, current practice can place a significant economic burden on the Russian healthcare system.

In the international literature, there are significantly more studies on the pharmacoeconomic evaluation of therapy for relapsed or refractory FL, in particular using mosunetuzumab — about 6 works were published just in 2024‑2025. Several of them were already considered in our previous publication [15]; new works also confirm the economic feasibility of broader implementation of mosunetuzumab in clinical practice for patients with relapsed or refractory FL.

Thus, the BIA results, regardless of the approach to estimating current practice costs, confirm the economic feasibility of using mosunetuzumab as 3rd and subsequent line therapy in adult patients with relapsed or refractory FL in Russia. The introduction of this regimen will help optimize budget expenditures and reduce the total economic burden on the healthcare system. Under budget constraints, the use of mosunetuzumab appears to be a rational solution, combining the clinical efficacy of innovative therapy with the principles of pharmacoeconomic efficiency.

Limitations of our study include:

• a short modeling horizon (1 year), due to the difficulty of predicting changes in the prescription structure of various therapy options for relapsed or refractory FL;

• the use of real‑world clinical practice data to estimate costs in the current scenario. This allows a more realistic reflection of the cost level for the considered patient cohort for the healthcare system; however, it may raise methodological questions regarding the conduct of BIA given its classic purpose — assessing the economic consequences of including drugs in the VED list within the SGP;

• in the current practice, in accordance with the recommendations of the CEQCMC, the costs of mosunetuzumab, which is already quite actively used in this patient group, were not taken into account. Also, the costs of CAR‑T therapy were not considered, as it is a biomedical cell product and its use is currently not fully covered by the SGP, which complicates cost estimation for its use. However, there is currently information about a domestic CAR‑T cell biomedical cell product “Utzhefra” developed by the National Medical Research Center of Hematology of the Ministry of Health of Russia [77]. According to their price list as of December 17, 2025, the cost of the medical service for organizing the collection of T‑cells, their processing, and the production of anti‑CD19 CAR‑T cell product (service code A18.05.017.011) is 5,702,160.00 rubles.

Conclusions

1. Cost analysis of drug therapy for 3rd and subsequent lines over 1 year per patient demonstrated high variability.

2. Total costs over 1 year of modeling amounted to 798.2 million rubles. During the indicated modeling period for current practice, the main share of costs is attributable to glofitamab (46.7%), followed by the R‑Ibr‑Lena regimen (7.5%) and G‑CVP (4.9%). That is, more than 75% of costs in current practice are spent on drugs that do not have an official indication for use in patients with relapsed or refractory FL in the 3rd and subsequent lines of therapy according to the instructions for medical use and the latest Russian clinical guidelines.

3. The BIA demonstrated that the use of mosunetuzumab in the 3rd and subsequent lines of therapy for patients with relapsed or refractory FL under the Russian healthcare system would save 24.9% or 199,087,769.09 rubles over 1 year. This would allow 32 new patients to start mosunetuzumab therapy within 1 year, thus expanding access to innovative therapy for patients without increasing funding.

4. Sensitivity analysis of the BIA results demonstrated the robustness of the model to changes in all input parameters, even when the cost of mosunetuzumab was doubled.