Drugs, Health Technologies, Health Systems
Indication: As monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy
Sponsor: Hoffmann-La Roche Limited
Recommendation: Reimburse with conditions
Summary
What Is the Reimbursement Recommendation for Lunsumio SC?
Canada’s Drug Agency (CDA-AMC) recommends that Lunsumio subcutaneous (SC) be reimbursed by public drug plans “as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy,” if certain conditions are met.
Why Did CDA-AMC Recommend Reimbursement?
The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that it is uncertain whether Lunsumio SC demonstrates acceptable clinical value in “adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy.” Given that Lunsumio SC is expected to be an alternative option for third-line and beyond therapy, acceptable clinical value refers to at least comparable value relative to other third-line and beyond therapies relevant in the context in Canada. Direct evidence from 1 clinical trial (GO29781) showed that treatment with Lunsumio SC resulted in response rate benefits considered clinically meaningful and durable by the CDA-AMC consulted experts and suggested potential survival benefits. Evidence from an indirect treatment comparison (ITC) suggested that overall survival (OS) and response outcomes with Lunsumio SC may be broadly comparable to other third-line and beyond therapies, although results were uncertain and mixed across comparisons. Uncertainty remains due to the single-arm study design, limited comparative evidence, and imprecision in indirect estimates. pERC concluded that, although the evidence suggests mosunetuzumab SC monotherapy has uncertain clinical value, given the rarity and severity of the condition the drug may address a significant unmet clinical need to a degree that justifies a positive recommendation despite the uncertainty in the clinical value.
pERC discussed the direct and indirect evidence and the clinical experts’ input and noted that the overall evidence suggested that Lunsumio SC may address a significant unmet clinical need, offering a chemotherapy-free, fixed-duration treatment with manageable safety profile that can be given in an outpatient setting, and is readily available, particularly for patients with limited access to existing therapies.
pERC noted significant unmet nonclinical needs and health inequities among patients with relapsed or refractory follicular lymphoma (r/r FL). pERC also noted that Lunsumio SC may improve access to care, as it can be provided off the shelf and administered outside specialized centres, potentially reducing travel, clinic visits, and reliance on tertiary care services, particularly for patients in rural or underserved settings. The committee considered the IV and SC formulations of Lunsumio to have comparable efficacy and safety and therefore preferred the SC formulation, while allowing flexibility based on patient preference and for individuals who may require IV administration due to substantial injection site reactions.
Based on all of the preceding considerations, pERC recommended that Lunsumio SC be reimbursed.
Which Patients Are Eligible for Coverage?
Lunsumio SC should only be covered for adults with histologically confirmed r/r FL (grades 1 to 3a) who have received at least 2 prior lines of systemic therapy, including an anti-CD20 therapy and an alkylating agent, and who have good performance status. Lunsumio SC should not be covered for patients with nonfollicular indolent lymphoma or a disease with central nervous system involvement.
What Are the Conditions for Reimbursement?
Lunsumio SC should be prescribed by clinicians experienced in managing hematologic malignancies and bispecific antibody-related complications, and given in settings with access to tocilizumab and appropriate supportive care. Reimbursement should be for a fixed duration of 8 or 17 cycles as per the drug’s product monograph and should be discontinued upon the occurrence of complete response, unacceptable toxicity, or disease progression. Re-treatment may be considered for patients whose disease relapses after a treatment-free interval of at least 6 months following completion of the initial treatment course.
The total cost of Lunsumio should not exceed the total cost of treatment with the least costly relevant chemotherapy comparator for the same indication.
Important budget impact considerations and organizational implications must be addressed for health systems to be able to adopt Lunsumio.
Disease background: FL is a systemic malignancy of lymphoid tissue characterized by germinal-centre B cell differentiation, typically presenting as a slow-progressing indolent non-Hodgkin lymphoma associated with common relapse and long survival measured in years. In Canada, it is estimated that more than 22,000 people were diagnosed with FL from 1992 to 2010, corresponding to an age-standardized incidence rate of 38 cases per million persons per year.
Indication and reimbursement request: Mosunetuzumab for SC injection (Lunsumio SC) has received a Notice of Compliance with Conditions (NOC/c) from Health Canada as a monotherapy for “adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy.” The sponsor is seeking reimbursement for this patient population.
Drug under review: Mosunetuzumab SC is a bispecific antibody inducing T cell-mediated B cell lysis. It is available as a 5 mg dose in a 2 mL vial containing 0.5 mL of solution (10 mg/mL), or as a 45 mg dose in a 2 mL vial containing 1 mL of solution (45 mg/mL), administered by SC injection. Mosunetuzumab SC should be administered for a fixed duration of 8 or 17 cycles based on tumour response, unless the patient experiences unacceptable toxicity or disease progression. The recommended dosage follows a step-up dosing regimen, consisting of 5 mg on cycle 1 day 1, 45 mg on cycle 1 day 8, and 45 mg on cycle 1 day 15, followed by 45 mg on day 1 of cycle 2 through cycle 8 if a complete response is achieved, or up to cycle 17 if disease stability or a partial response is observed.
Treatment costs: At the submitted price of $1,518.70/5 mg solution, the cost of mosunetuzumab SC is expected to be $38,474 per patient for the first 28-day cycle and $18,224 per patient for subsequent 28-day cycles, based on the Health Canada–recommended dosage.
The patient group (Lymphoma Canada) noted the following regarding impacts of the disease, unmet needs, and important outcomes:
FL is associated with physical symptoms such as fatigue, lymph node swelling, abdominal discomfort, night sweats, and body pain, along with psychological and practical impacts including stress and anxiety, fear of progression, sleep difficulties, frequent health care visits, and reduced daily functioning.
Important treatment outcomes for patients include prolonged survival, durable disease and symptom control, longer remission, improved quality of life, fewer side effects, and predictable benefits.
The clinician groups (Leukemia and Lymphoma Society Nurses Network, Ontario Health [Cancer Care Ontario] Hematology Cancer Drug Advisory Committee, and Lymphoma Canada) and the clinical experts consulted by CDA-AMC noted the unmet needs arising from the disease as follows:
There is an ongoing need for effective, well-tolerated, chemotherapy-free, and time-limited outpatient treatment options for r/r FL, particularly in later lines of therapy and for patients with limited tolerance for intensive treatments or barriers to access.
Mosunetuzumab SC is anticipated to be used primarily as a later-line outpatient treatment option for adults with r/r FL, including patients who are ineligible for, unable to access, or prefer to avoid CAR T-cell therapy, and as a potential option following disease relapse after CAR T-cell treatment.
The participating public drug programs raised potential implementation issues related to relevant comparators, considerations for initiation and prescribing of therapy, generalizability of trial populations to broader populations, potential need for a provisional funding algorithm, care provision issues, and system and economic issues.
With a vote of 12 in favour to 4 against, pERC recommends that mosunetuzumab SC be reimbursed “as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy” only if the conditions listed in Table 1 are met.
Table 1: Reimbursement Conditions and Reasons
Reimbursement condition | Reason | Implementation guidance |
|---|---|---|
Initiation | ||
1. Mosunetuzumab SC should be reimbursed in adults with r/r FL (grades 1 to 3a) who meet all the following criteria: 1.1. histologically confirmed FL (grades 1 to 3a) 1.2. r/r to 2 or more previous lines of treatment, including an anti-CD20 therapy and an alkylating agent 1.3. have a good performance status. | Evidence from the GO29781 study demonstrated (and clinical experts consulted by CDA-AMC indicated) that treatment with mosunetuzumab SC may provide a clinical benefit in patients with the characteristics listed in this condition. The GO29781 study enrolled patients who had an ECOG PS score of 0 or 1. | Condition 1.2:
Condition 1.3: Based on the clinical experts’ input, selected patients with an ECOG PS score of 2 could be considered for treatment with mosunetuzumab SC at the discretion of the treating physician. |
2. Patients are ineligible for treatment with mosunetuzumab if they have any of the following criteria: 2.1. nonfollicular indolent lymphoma 2.2. CNS involvement. | Patients with nonfollicular indolent lymphoma or CNS involvement were not included in the GO29781 study. The clinical experts noted that conditions such as marginal zone lymphoma and chronic lymphocytic leukemia have biological behaviour that differs from FL, and that FL rarely involves the CNS. As a result, these patient populations were excluded from the study, and the evidence is therefore not generalizable to these groups. | pERC considered mosunetuzumab appropriate for patients who are ineligible for, unable to access, or decline CAR T-cell therapy, but not as a preferred alternative for eligible patients with adequate access to CAR T-cell therapy. |
Renewal | ||
3. Reimbursement of re-treatment with mosunetuzumab SC could be considered if a patient experiences r/r FL after a treatment-free interval of at least 6 months following the initial 8 or 17 cycles of treatment. | Re-treatment after a complete response and discontinuation at 8 cycles was allowed in the GO29781 study. pERC confirmed that a minimum disease-free interval (remission) of at least 6 months is required. The clinical experts emphasized that CD20 expression should be reassessed at disease relapse, as a biopsy is standard practice and CD20 down regulation may occur under selective pressure from CD20 targeted therapies. Re-treatment after completing 17 cycles may also be considered, depending on clinical context and prior tolerability. | The clinical experts noted that response should be assessed using imaging (CT or PET) after 8 cycles and again at the end of therapy, consistent with trial practice and routine standards in Canada. Interim imaging before the end of cycle 8 is recommended to determine whether treatment should stop at 8 cycles for patients who achieve a complete response or continue to 17 cycles for patients who achieve a partial response. The clinical experts indicated that these assessments align with the clinical practice in Canada and are feasible to implement. |
Discontinuation | ||
4. Reimbursement of mosunetuzumab SC should be discontinued upon occurrence of any of the following: 4.1. complete response 4.2. unacceptable toxicity 4.3. disease progression. | In the GO29781 study, mosunetuzumab SC treatment was discontinued if a patient experienced disease progression or intolerable AEs. | Per the drug’s product monograph, for patients who achieve a complete response, no further treatment beyond 8 cycles is required, and for patients who achieve a partial response or have disease stability in response to treatment with mosunetuzumab SC after 8 cycles, an additional 9 cycles of treatment (17 cycles total) could be administered, unless a patient experiences unacceptable toxicity or disease progression. |
Prescribing | ||
5. Mosunetuzumab SC should only be prescribed by clinicians experienced in managing hematologic malignancies and the complications of bispecific antibody therapy (e.g., CRS and ICANS) and administered in a setting with access to tocilizumab and appropriate supportive care. | This is meant to ensure that mosunetuzumab SC is prescribed for appropriate patients and that adverse effects are managed in an optimized and timely manner. | pERC considered that the IV and SC formulations of mosunetuzumab have comparable efficacy and safety. The committee discussed clinical experts' input indicating that SC administration is generally preferred by patients and health care systems due to reduced health system resource use (e.g., chair time, compounding time) and a more favourable safety profile. Accordingly, pERC determined that the mosunetuzumab SC be prioritized over the IV formulation, with flexibility for patients’ preference and the occasional patient who may experience significant injection site reactions, for whom IV administration may be more suitable. |
6. Mosunetuzumab SC should be administered as monotherapy. | In the GO29781 study, mosunetuzumab SC was administered as a monotherapy. | — |
Pricing | ||
7. The total cost of mosunetuzumab SC should be negotiated so that it does not exceed the total cost of treatment with the least costly relevant chemotherapy comparator for the same indication. | Based on the committee’s assessment of the evidence, mosunetuzumab SC is expected to have similar clinical benefits and harms compared with relevant comparators. Therefore, the total cost of mosunetuzumab SC should be no more than the least costly relevant chemotherapy regimen. | — |
Feasibility of adoption | ||
8. The economic feasibility of adoption of mosunetuzumab SC must be addressed. | At the submitted price, the magnitude of uncertainty in the budget impact must be addressed to ensure the feasibility of adoption, given the difference between the sponsor’s estimate and the estimate from CDA-AMC. | — |
AE = adverse event; CDA-AMC = Canada’s Drug Agency; CNS = central nervous system; CRS = cytokine release syndrome; ECOG PS = Eastern Cooperative Oncology Group Performance Status; FL = follicular lymphoma; ICANS = immune effector cell associated neurotoxicity syndrome; pERC = pan-Canadian Oncology Drug Review Expert Review Committee; r/r = relapsed or refractory; SC = subcutaneous.
Based on the totality of the clinical evidence, pERC noted that it is uncertain whether mosunetuzumab SC monotherapy demonstrates acceptable clinical value in “adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy.” Given that mosunetuzumab SC is expected to be an alternative option for third-line and beyond therapy, acceptable clinical value refers to at least comparable value relative to other third-line and beyond therapies relevant in the context in Canada. pERC concluded that, although the evidence suggests mosunetuzumab SC monotherapy has uncertain clinical value, given the rarity and severity of the condition the drug may address a significant unmet clinical need to a degree that justifies a positive recommendation despite the uncertainty in the clinical value
One phase I (1b)/II, single-arm, open-label study (GO29781, N = 94) provided evidence regarding the efficacy and safety of mosunetuzumab SC monotherapy in “adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy.” In a median observation time of 20.7 months, the complete response rate (CRR) was 58.5% (95% confidence interval [CI], 47.9% to 68.6%), and the overall response rate (ORR) (partial or complete response) was 74.5% (95% CI, 64.4% to 82.9%). The clinical experts consulted by CDA-AMC considered the response rates observed in the GO29781 study to be clinically meaningful in the context of expected outcomes for adult patients with r/r FL (grades 1 to 3a) undergoing third-line and beyond therapy. Mosunetuzumab SC was associated with potential benefits in survival outcomes. At the clinical data cut-off of February 2024, median OS was not reached, and the Kaplan-Meier survival probability at 18 months was 89.6% (95% CI, 82.5% to 96.6%). At the clinical data cut-off of July 2024, the median progression-free survival (PFS) was 23.7 months (95% CI, 14.6 months to not estimable). Cytokine release syndrome was among the notable harms and aligned with the known safety profile of mosunetuzumab. Overall, the safety findings from the GO29781 study were consistent with the established risks of the bispecific antibody drug class, with no unexpected signals identified.
Evidence from the sponsor-submitted ITC evaluating the effects of mosunetuzumab monotherapy versus relevant comparators, indicated some uncertainty in the OS and ORR results across comparisons, with estimates suggesting that outcomes may be comparable between treatments. Results for PFS, CRR, and treatment discontinuation due to adverse events (AEs) showed mixed results across comparisons, with some analyses favouring comparator therapies (e.g., axicabtagene ciloleucel, tisagenlecleucel, or obinutuzumab plus bendamustine for PFS; axicabtagene ciloleucel for CRR), others favouring mosunetuzumab (e.g., compared to rituximab plus lenalidomide and obinutuzumab plus bendamustine for CRR, and compared to obinutuzumab plus bendamustine for treatment discontinuation due to AEs), and several comparisons remaining uncertain. Overall, the ITC evidence was very uncertain due to imprecision, limited sample size, and limitations in the assumptions underlying the model.
pERC acknowledged that patients identified a need for more effective, well-tolerated, and accessible treatment options in later lines of therapy, particularly those that reduce cumulative toxicity, treatment burden, and barriers related to travel and availability. The committee also noted clinicians emphasized the need for novel, noncross-resistant therapies that can provide durable responses, are chemotherapy-free, and can be delivered conveniently in outpatient or community settings in an SC formulation, given the limitations and restricted accessibility of CAR T-cell therapy. pERC considered the uncertainties in the evidence due to the limitations in the studies, including the single-arm design of the GO29781 trial. The committee also considered the clinical experts’ observation that the CRR and ORR were clinically meaningful for the population of patients, especially those with limited access to or unable to receive certain therapies. Therefore, pERC determined that mosunetuzumab SC represents an alternative immunotherapy option for “adult patients with relapsed or refractory follicular lymphoma (Grades 1 –3a) who have received at least two prior lines of systemic therapy” that may address some of these unmet needs by offering a fixed-duration, outpatient treatment with a manageable safety profile.
Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.
pERC acknowledged that there is a significant unmet clinical need for patients with r/r FL (grades 1 to 3a), particularly in the third-line setting and beyond. This reflects the incurable and relapsing nature of the disease, diminishing effectiveness and durability of available treatments with successive lines, cumulative toxicities, and limited access to certain therapies (e.g., CAR T-cell therapy) due to eligibility, logistical, and geographic constraints. Patients and clinicians emphasized the need for effective, well-tolerated, chemotherapy-free, and accessible outpatient treatment options that can provide durable disease control and reduce treatment burden.
Further information on the committee’s discussion around unmet clinical need is provided in the Summary of Deliberation section.
pERC noted that there are significant unmet nonclinical needs and health inequities for patients with r/r FL. These include barriers to accessing specialized treatments (e.g., CAR T-cell therapy), particularly for patients who are older, experiencing frailty, or living in rural or remote areas, as well as the logistical burden of frequent clinic visits, travel to tertiary centres, and prolonged treatment administration. The committee observed that socioeconomic factors and geographic distance disproportionately limit access for marginalized populations who face barriers to care or are at increased risk for r/r FL.
pERC considered that the fixed-duration, outpatient administration, an SC formulation, and off the shelf availability of mosunetuzumab SC may help address unmet nonclinical needs and inequities by reducing treatment burden and improving access, particularly for patients in rural or remote areas.
Further information on the committee’s discussion around unmet nonclinical need is provided in the Distinct Social and Ethical Considerations domain in the Summary of Deliberation section.
Due to the uncertainty in clinical value, pERC could not recommend whether to reimburse mosunetuzumab SC or not based on clinical value alone. Therefore, they also considered whether mosunetuzumab SC addresses a significant unmet clinical need. pERC concluded that mosunetuzumab SC addresses a significant unmet clinical need with an acceptable level of certainty. Based on the preceding considerations, pERC recommended that mosunetuzumab SC be reimbursed. As part of the deliberation on whether to recommend reimbursement or not, the committee also considered unmet nonclinical need and health inequity. Information on this discussion is provided in the Distinct Social and Ethical Considerations domain in the Summary of Deliberation section.
Because pERC recommended that mosunetuzumab SC be reimbursed, the committee also deliberated on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations, or to ensure clinical value is realized. The resulting reimbursement conditions, with accompanying reasons and implementation guidance, are stated in Table 1.
pERC considered all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, refer to Expert Committee Deliberation at Canada’s Drug Agency.
The committee considered the following key discussion points, organized by the 5 domains of value.
Appropriate comparators: pERC noted that axicabtagene ciloleucel and tisagenlecleucel are the most relevant treatment options, as CAR T-cell therapy is the standard of care in the third-line setting and beyond. Other treatments considered relevant comparators were rituximab, rituximab plus bendamustine, rituximab plus lenalidomide, obinutuzumab plus bendamustine, idelalisib, a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and a combination of rituximab, cyclophosphamide, vincristine, and prednisone.
Efficacy from a single-arm study: Evidence from the GO29781 study, showed that after a median observation time of 20.7 months, the CRR was 58.5% (95% CI, 47.9% to 68.6%), and the ORR was 74.5% (95% CI, 64.4% to 82.9%). At the clinical data cut-off of February 2024, median OS was not reached, and the Kaplan-Meier survival probability at 18 months was 89.6% (95% CI, 82.5% to 96.6%). At the clinical data cut-off of July 2024, the median PFS was 23.7 months (95% CI, 14.6 months to not estimable). At cycle 8, 35% of patients in the SC cohort had an improvement of at least 3 points from baseline in the Functional Assessment of Cancer Therapy–Lymphoma subscale score. The notable harm (cytokine release syndrome) was consistent with the known safety profile of mosunetuzumab. pERC concluded that the treatment effects of mosunetuzumab are very uncertain because it was not compared with any other treatment in the GO29781 study. Immune effector cell associated neurotoxicity syndrome was reported by 3 patients (3.2%), and the risk of immune effector cell associated neurotoxicity syndrome remains uncertain due to the small sample size. Eight of 94 patients (8.5%) experienced fatal (grade 5) AEs. pERC noted that the study (SC cohort) was conducted during the COVID-19 pandemic, and the leading causes of death were COVID-19 (3 of 8) and disease progression (3 of 8), with general health deterioration and hemophagocytic lymphohistiocytosis each accounting for 1 of the 8 deaths.
Clinical importance of treatment effects: Patients identified longer survival, durable disease and symptom control, longer remission, improved quality of life, and fewer side effects as the most important treatment outcomes. Patients also emphasized the importance of having treatment choice, predictable benefits, and therapies that balance effectiveness with tolerability to minimize treatment burden and preserve daily functioning. Based on expert input, the response rates were clinically meaningful in the context of expected outcomes for adult patients with r/r FL (grades 1 to 3a) undergoing third-line or later therapy. The health-related quality of life results in the GO29781 study were inconclusive because of its single-arm design and missingness of data. pERC considered that despite the uncertainty in the evidence from the GO29781 study, mosunetuzumab SC represents an alternative immunotherapy option for patients with r/r FL (grades 1 to 3a), particularly in the third-line setting and beyond.
Certainty of the evidence: In the absence of a comparator group in the GO29781 study, a Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment rated the certainty of evidence from the study as very low and a conclusion regarding the efficacy of mosunetuzumab SC relative to other treatments could not be drawn.
Efficacy versus relevant third-line and beyond therapies: Three matching-adjusted indirect comparisons and 4 propensity score analyses showed uncertainty in the OS and ORR results across comparisons, with estimates suggesting that outcomes may be comparable between treatments. Results for PFS, CRR, and treatment discontinuation due to AEs were inconclusive due to limitations such as small sample sizes and analytical assumptions. Across all comparisons, it remains unclear whether the assumptions underlying these analyses were met and whether treatment effect modifiers and prognostic variables were adequately adjusted for. Considering the limitations noted in the ITCs, including serious imprecision, small sample sizes, decreases in the number of patients at risk over follow-up, and violations of model assumptions for some comparisons, pERC considered the findings insufficient to draw firm conclusions on the relative efficacy or safety of mosunetuzumab compared with the comparators. pERC agreed with clinical experts that mosunetuzumab may be offered to patients who are ineligible for CAR T-cell therapy or face barriers to access. However, pERC agreed with clinical experts that in eligible patients with reasonable access, CAR T-cell therapy would be preferred over mosunetuzumab in the third-line setting and beyond.
Clinical value: Based on the preceding considerations, pERC determined that mosunetuzumab SC would provide an alternative treatment option in “adult patients with relapsed or refractory follicular lymphoma (Grades 1 – 3a) who have received at least two prior lines of systemic therapy,” especially in those for whom current treatments are inaccessible or unsuitable.
Input on unmet clinical need: Patients identified a need for more effective, durable, and well-tolerated treatment options in later lines of therapy, along with improved access and reduced treatment burden. They highlighted challenges related to side effects, frequent hospital visits, and travel, which affect quality of life. Clinical experts and clinician groups similarly emphasized the need for therapies that provide longer remission, limit cumulative toxicity, and offer options for patients who are ineligible for or unable to access CAR T-cell therapy. These unmet needs contribute to declining response rates, shorter remissions, reduced quality of life, and inequitable access to care, particularly for those living in rural or remote areas.
Severity of the disease: pERC acknowledged that FL is an incurable, indolent malignancy that typically requires ongoing treatment, with many patients receiving multiple lines of therapy that become progressively less effective and less durable over time. Clinical experts consulted by CDA-AMC noted that FL accounts for approximately 20% to 30% of non-Hodgkin lymphoma, which is the fifth most common cancer in Canada.
Availability of treatment options: Available treatments for r/r FL in the third-line and later setting include chemoimmunotherapy regimens (e.g., rituximab-based combinations), rituximab plus lenalidomide, obinutuzumab plus bendamustine, and CAR T-cell therapies (axicabtagene ciloleucel and tisagenlecleucel). Clinical experts and clinician group input indicated that the effectiveness of these options declines with successive lines of therapy, with shorter remission durations and increasing toxicity. Patients, clinicians, and clinical experts identified important gaps, including limited durability of response, cumulative treatment burden, access barriers (particularly for CAR T-cell therapy and for those living in rural or remote areas), and the lack of well-tolerated, chemotherapy-free, fixed-duration, SC formulation, outpatient options that preserve quality of life.
Input on unmet nonclinical need: Patient and clinician groups identified important unmet nonclinical needs and health inequities for patients with r/r FL. These include barriers to accessing specialized therapies (e.g., CAR T-cell therapy), particularly for patients who are older, experiencing frailty, or living in rural or remote areas, as well as the burden associated with frequent clinic visits, travel to tertiary centres, and prolonged treatment administration. Socioeconomic and geographic factors were noted to further limit access for marginalized populations who face barriers to care or are at increased risk for r/r FL. pERC acknowledged that mosunetuzumab SC may help address some of these needs by offering a fixed-duration, SC formulation, outpatient treatment; however, uncertainty regarding its comparative benefit remains due to the lack of head-to-head evidence.
Equity considerations: pERC noted that geographic location, particularly residence in rural or remote areas, along with socioeconomic status, may limit access to specialized therapies and contribute to inequities in care. pERC concluded that treatments that can be delivered in outpatient or community settings may help reduce travel burden and improve access, although persistent system-level barriers may continue to affect equitable access across patient populations.
Significant unmet nonclinical need or health inequity: pERC observed that barriers to access for some specialized therapies (e.g., CAR T-cell therapy), as well as the logistical burden of frequent clinic visits, travel to tertiary centres, and prolonged treatment administration due to socioeconomic factors and geographic distance disproportionately affect marginalized populations who face barriers to care or are at increased risk for r/r FL. pERC acknowledged that the fixed-duration, SC formulation, outpatient administration and off the shelf availability of mosunetuzumab SC may help address certain unmet nonclinical needs and inequities.
Health impacts of mosunetuzumab SC versus relevant comparators: The relative impact of mosunetuzumab SC on patient health is very uncertain due to uncertainty in the findings from the ITCs. Based on evidence reviewed for this submission, there is no robust evidence to suggest that mosunetuzumab SC provides greater health benefit than rituximab plus lenalidomide, obinutuzumab plus bendamustine, rituximab plus bendamustine, axicabtagene ciloleucel, or tisagenlecleucel.
Cost of mosunetuzumab SC versus relevant comparators: Based on the submitted price of mosunetuzumab SC, it is expected to increase health care system costs if reimbursed by public drug plans when compared to rituximab plus lenalidomide, obinutuzumab plus bendamustine, and rituximab plus bendamustine. Drug acquisition costs were the primary driver of incremental costs between mosunetuzumab SC and these comparators. Relative to axicabtagene ciloleucel and tisagenlecleucel, the committee discussed that the impacts to health system costs are very uncertain due to the one-time cost of CAR T-cell treatment and will depend on length of treatment of mosunetuzumab SC.
Key findings of the economic evaluation: The indirect evidence for mosunetuzumab SC versus comparators is very uncertain and there is insufficient evidence to determine whether mosunetuzumab SC provides greater health benefit compared to relevant comparators. Due to the lack of robust clinical evidence, no CDA-AMC base case was performed, and therefore no incremental cost-effectiveness ratio was estimated by CDA-AMC.
Certainty of the evidence: Several limitations regarding the ITC used to inform the comparison for mosunetuzumab SC versus all comparators were identified by the CDA-AMC review team such as heterogeneity, unmeasured confounding, population differences, and small sample size, in addition to residual uncertainty inherent in the indirect comparisons. For all comparisons, it is unclear whether assumptions underlying the ITCs were met and whether treatment effect modifiers and prognostic variables were appropriately adjusted for.
Other considerations: Tafasitamab in combination with rituximab plus lenalidomide is currently being reviewed by CDA-AMC for the treatment of patients with r/r FL (grades 1 to 3a). Clinical experts consulted by CDA-AMC noted that it may be currently accessible to patients through compassionate use programs.
Anticipated budget impact: CDA-AMC estimated that in year 3 of reimbursement, 585 patients would be eligible for mosunetuzumab SC; of these, 351 patients are expected to receive mosunetuzumab SC. The estimated incremental budget impact of reimbursing mosunetuzumab SC is predicted to result in savings of approximately $6 million over the first 3 years of reimbursement compared to the amount currently spent on comparators, with an estimated expenditure of $109 million on mosunetuzumab SC for this period. The actual budget impact of reimbursing mosunetuzumab SC will depend on which treatments are displaced by mosunetuzumab SC, the market uptake of mosunetuzumab SC, and the confidential list prices of comparators. Additionally, the magnitude of uncertainty in the budget impact must be addressed to ensure the feasibility of adoption given the difference between the sponsor’s estimate and the estimate from CDA-AMC. If CAR T is not displaced by mosunetuzumab SC, there would no longer be cost savings associated with reimbursing mosunetuzumab SC. The budget impact of reimbursing mosunetuzumab SC in patients who are ineligible for CAR T therapy is unknown.
Organizational implications: pERC acknowledged that the SC administration of mosunetuzumab would be generally preferred compared to IV administration by patients and health care systems due to reduced health system resource use (e.g., chair time, compounding time).
To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project webpage):
the CDA-AMC review of the clinical and pharmacoeconomic evidence submitted by the sponsor, as well as relevant ethical issues related to mosunetuzumab SC (refer to the Main Report and Supplemental Material document)
the sponsor’s comments on the draft report and the responses by CDA-AMC
patients' perspectives gathered by 1 patient group, Lymphoma Canada (refer to the Patient and Clinician Group Input document)
input from 3 clinician groups, Leukemia and Lymphoma Society Nurses Network, Ontario Health (Cancer Care Ontario) Hematology Cancer Drug Advisory Committee, and Lymphoma Canada (refer to the Patient and Clinician Group Input document)
input from public drug programs that participate in the reimbursement review process (refer to the Supplemental Material document)
input from 2 clinical experts with expertise in the management of FL consulted by CDA-AMC.
All feedback received in response to the draft recommendation is available on the CDA-AMC website.
Dr. Catherine Moltzan (Chair), Dr. Kelvin Chan (Vice-Chair), Paul Agbulu, Dr. Phillip Blanchette, Dr. Matthew Cheung, Dr. Michael Crump, Annette Cyr, Dr. Jennifer Fishman, Dr. Jason Hart, Terry Hawrysh, Dr. Yoo-Joung Ko, Dr. Aly-Khan Lalani, Amy Peasgood, Dr. Anca Prica, Dr. Michael Raphael, Dr. Adam Raymakers, Dr. Patricia Tang, Dr. Pierre Villeneuve, and Danica Wasney.
Meeting date: May 13, 2026
Regrets: One expert committee member did not attend.
Conflicts of interest: None
ISSN: 2563-6596
Canada’s Drug Agency (CDA-AMC) is a pan-Canadian health organization. Created and funded by Canada’s federal, provincial, and territorial governments, we’re responsible for driving better coordination, alignment, and public value within Canada’s drug and health technology landscape. We provide Canada’s health system leaders with independent evidence and advice so they can make informed drug, health technology, and health system decisions, and we collaborate with national and international partners to enhance our collective impact.
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