Drugs, Health Technologies, Health Systems
Indication: Tafasitamab in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified, including diffuse large B-cell lymphoma arising from low grade lymphoma, who are not eligible for autologous stem cell transplant
Sponsor: Incyte Biosciences Canada Corporation
Final recommendation: Do not reimburse
Summary
What Is the Reimbursement Recommendation for Minjuvi?
Canada’s Drug Agency (CDA-AMC) recommends that Minjuvi not be reimbursed by public drug plans for adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for autologous stem cell transplant (ASCT), and have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2 or less.
Why Did CDA-AMC Not Recommend Reimbursement?
CDA-AMC previously reviewed Minjuvi plus lenalidomide in 2022 for the treatment of adult patients with r/r DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, who are not eligible for ASCT, and issued a recommendation of not to reimburse. This is a resubmission based on a post hoc defined subpopulation of the L-MIND study which excluded patients with primary refractory disease and those with unconfirmed DLBCL histology. The resubmission included additional longer follow-up and health-related quality of life (HRQoL) data to address the gaps identified in the previous recommendation.
The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that it is uncertain whether Minjuvi demonstrates acceptable clinical value versus appropriate comparators in adult patients with r/r DLBCL not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for ASCT, and have an ECOG PS score of 2 or less. Appropriate comparators refer to polatuzumab vedotin-bendamustine-rituximab (pola-BR), rituximab-gemcitabine-oxaliplatin (R-GemOx), glofitamab-gemcitabine-oxaliplatin (glofit-GemOx), epcoritamab, and glofitamab.
Evidence from a subpopulation of patients enrolled in the phase II, open-label, single-arm L-MIND trial showed that treatment with Minjuvi in combination with lenalidomide resulted in clinically meaningful objective responses (i.e., partial or complete tumour responses) in patients with r/r DLBCL who did not have primary refractory disease and were ineligible for ASCT. However, the magnitude of clinical benefit attributable to tafasitamab plus lenalidomide remains uncertain because the evidence was derived from a small, post hoc subgroup within a nonrandomized and noncomparative study design. HRQoL, which is important for patients, was not assessed in the L-MIND trial, and the available real-world evidence was descriptive and may not be generalizable to patients in Canada. The committee reviewed additional evidence from 2 sponsor-submitted indirect treatment comparisons (ITCs) comparing Minjuvi plus lenalidomide with R-GemOx. However, important methodological limitations of ITCs precluded pERC from drawing firm conclusions regarding the comparative efficacy and safety of Minjuvi plus lenalidomide versus R-GemOx. No comparative evidence versus other relevant treatment options was available.
The committee considered whether the drug would address significant unmet clinical or nonclinical needs. pERC acknowledged an unmet need for additional treatment options for patients with r/r DLBCL who are ineligible for ASCT, particularly treatments that prolong survival and remission, control symptoms, improve HRQoL, and have manageable side effects. However, the committee was unable to determine that Minjuvi plus lenalidomide addresses this unmet need with an acceptable level of certainty in clinical value because of the absence of comparative evidence versus other relevant treatment options and uncertainty regarding its efficacy, safety, HRQoL benefits, and tolerability in this patient population. The committee also acknowledged health inequities for patients with r/r DLBCL, including geographic and logistical barriers to accessing specialized therapies. However, pERC was unable to determine whether Minjuvi plus lenalidomide adequately addressed these unmet nonclinical needs and health inequities, as the treatment requires frequent infusions and access to infusion services, which may remain challenging for some patients.
Based on all of the preceding considerations, pERC recommended that Minjuvi plus lenalidomide not be reimbursed.
Disease background: DLBCL is a subtype of non-Hodgkin lymphoma (NHL), a cancer that forms in the lymphatic system. It is an aggressive form of B-cell lymphoma that can arise on its own or evolve from other types like follicular lymphoma. In Canada, DLBCL is the most common type of NHL, making up about 30% to 40% of cases, or about 5.6 people per 100,000 each year. r/r DLBCL refers to disease that either returns after initially responding to treatment (relapsed), which occurs in approximately 20% to 30% of patients after first-line therapy, or does not respond to treatment at all (refractory).
Indication and reimbursement request: Tafasitamab (Minjuvi) has been approved by Health Canada in combination with lenalidomide for the treatment of adult patients with r/r DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, who are not eligible for ASCT. The sponsor is seeking reimbursement for the treatment of adult patients with r/r DLBCL not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for ASCT, and have an ECOG PS score of 2 or less.
Drug under review: Tafasitamab is a CD19-targeting monoclonal antibody that induces B-cell lysis. It is available as a lyophilized powder for solution for administration by IV infusion. The dosage of tafasitamab recommended in the product monograph is 12 mg/kg, administered on days 1, 4, 8, 15, and 22 for cycle 1, once weekly for cycles 2 to 3 and once every 2 weeks for cycles 4 to 12. Tafasitamab is administered with oral lenalidomide 25 mg daily for 12 cycles (on days 1 to 21 of each cycle). The regimen consists of a total of twelve 4-week cycles. After 12 cycles, lenalidomide is stopped, and tafasitamab continues alone.
Treatment costs: At the submitted price of $1,167.86 per 200 mg vial, the per 28-day cost of tafasitamab is expected to be $29,197 per patient in the first cycle; $23,357 per patient in the second and third cycle of treatment; and $11,679 in subsequent cycles, based on the Health Canada–recommended dosage. Tafasitamab is indicated for use in combination with lenalidomide; the per 28-day cost of the regimen is expected to be $31,423 per patient for the first cycle; $25,583 for the second and third cycles of treatment; $13,905 for cycles 4 to 12 of treatment; and $11,679 for subsequent cycles. Treatment costs were calculated based on a weight of 76 kg.
Submission history: Tafasitamab was previously reviewed by CDA-AMC in combination with lenalidomide and received a recommendation not to reimburse for the treatment of adult patients with r/r DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, who are not eligible for ASCT from pERC on September 26, 2022. The original review of tafasitamab included 1 phase II, noncomparative single-arm, open-label study (L-MIND; N = 81). In its assessment of the clinical evidence, pERC concluded that the L-MIND study provided highly uncertain evidence regarding the magnitude of clinical benefit attributable to tafasitamab plus lenalidomide. The nonrandomized design, lack of a control arm, and small sample size limited the ability to determine treatment effects with confidence, and the potential benefit of tafasitamab plus lenalidomide relative to relevant comparators was unknown. HRQoL was also not assessed in L-MIND. Although the study demonstrated antitumour activity, the clinical meaningfulness of these findings was considered uncertain due to the absence of a comparator, formal statistical testing, lack of HRQoL data, and small sample size. While progression-free survival (PFS) and overall survival (OS) appeared longer than typically expected in patients with r/r DLBCL, pERC noted that it remained unclear whether these outcomes are attributable to treatment, given the favourable patient profile enrolled in the trial and the limited generalizability to clinical practice in Canada. ITCs suggested a possible benefit compared to other regimens; however, substantial methodological limitations prevented definitive conclusions regarding relative efficacy. Overall, pERC found that it remains uncertain whether tafasitamab plus lenalidomide meets key patient needs, including improvements in survival, symptoms, quality of life, and safety.
Basis of resubmission: The sponsor filed a resubmission based on evidence from a post hoc defined subpopulation of the L-MIND study which excluded patients with primary refractory disease, and those with unconfirmed DLBCL histology. The sponsor’s rationale for excluding patients with primary refractory disease was based on 3 main grounds: the L-MIND study was not designed to evaluate tafasitamab plus lenalidomide in this population, primary refractory DLBCL represents a more aggressive disease state associated with a significantly poorer prognosis, and clinical guidelines by the European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) recommend tafasitamab plus lenalidomide in second-line therapy and beyond, excluding patients with primary refractory disease. The revised reimbursement request is for tafasitamab in combination with lenalidomide for the treatment of adult patients with r/r DLBCL not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for ASCT, and have an ECOG PS score of 2 or less. The resubmission included additional data with longer follow-up (5 years) and data for HRQoL to address the committee’s prior concerns on generalizability of the data included in the original submission.
The patient group (Lymphoma Canada) noted the following regarding impacts of the disease, unmet needs, and important outcomes:
Patients experienced substantial physical (e.g., fatigue, pain, night sweats) and psychosocial burden (e.g., anxiety, sleep issues), along with delays in diagnosis or treatment and frequent health care visits that contribute to financial and daily life impacts.
Disease and treatment limited daily functioning (e.g., work, travel, household activities, social life), with many patients requiring multiple lines of therapy (more than one-half were receiving ≥ 2 lines).
Patients identified ongoing needs for effective and accessible treatments, particularly in later lines of therapy, citing challenges related to access, geography, and financial burden. They emphasized a strong need for additional well-tolerated options, especially for those not eligible for intensive therapies.
Patients prioritized longer survival and remission, symptom control, improved quality of life, fewer side effects, and having treatment choices aligned with their preferences and daily life.
The clinician groups (Ontario Health [Cancer Care Ontario] Hematology Cancer Drug Advisory Committee and the Ad Hoc Group of Ontario Medical Oncologists and Hematology-Oncologists along with Lymphoma Canada's Scientific Advisory Board) and the clinical experts consulted by CDA-AMC noted the following regarding unmet needs arising from the disease and place in therapy for the drug under review:
Current treatments often lack durable benefit, can be highly toxic, and place substantial access and logistical burdens on patients, especially those in rural or remote areas; inequities in access to advanced therapies and supportive care remain a concern.
There is a continued need for effective, well-tolerated, and accessible therapies for patients with limited options (for example, those ineligible for intensive treatment or with refractory disease), as well as treatments that improve quality of life and reduce overall treatment burden.
Tafasitamab plus lenalidomide is expected to be used as a chemotherapy-free, CD19-targeted option in the second or third line for patients with r/r DLBCL who are not eligible for ASCT, CAR T-cell therapy, bispecific antibodies, or other intensive regimens. It may be suitable for older patients or those with significant comorbidities but would typically be considered after preferred alternatives based on eligibility and treatment goals.
The participating public drug programs raised potential implementation issues related to considerations for relevant comparators, initiation, and prescribing of therapy; generalizability of trial populations to broader populations; care provision issues; system and economic issues; and potential need for a provisional funding algorithm.
With a vote of 16 to 0, pERC recommends that tafasitamab not be reimbursed in combination with lenalidomide for the treatment of adult patients with r/r DLBCL not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for ASCT, and have an ECOG PS score of 2 or less.
The pERC recommendation dated September 26, 2022, for tafasitamab in combination with lenalidomide for the treatment of adult patients with r/r DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, who are not eligible for ASCT continues to apply to patients who are not included in the population evaluated in this resubmission.
In this resubmission, the evidence from the phase II, open-label, single-arm L-MIND study was restricted to a subpopulation of ██ of the original 81 patients with r/r DLBCL who were ineligible for ASCT. This subgroup excluded patients with primary refractory disease ██████, those without centrally confirmed DLBCL █████, and ███ ███████ who did not receive treatment ██████
Although █████ (95% confidence interval [CI], █████ ██ █████) of patients from the L-MIND study subpopulation showed an objective response of complete or partial response, there was still a high degree of uncertainty regarding the magnitude of clinical benefit directly attributable to tafasitamab plus lenalidomide due to the nonrandomized, noncomparative, open-label study design and the small sample size. Further, due to the absence of a comparator arm, the potential clinical benefit of tafasitamab plus lenalidomide compared to other relevant treatment comparators is unknown. HRQoL was also not assessed in the L-MIND study and the small real-world study evaluating HRQoL in patients with DLBCL in Italy was descriptive and may not be generalizable to the patients in Canada. The sponsor submitted 2 ITCs that compared patients in the L-MIND study to patients treated with R-GemOx. However, given the methodological limitations of the analyses (i.e., heterogeneity, matching based on a limited number of variables, and small sample sizes), pERC could not determine the comparative efficacy of tafasitamab plus lenalidomide relative to R-GemOx. There was no comparative data on harms; thus, no conclusions could be drawn regarding the relative safety of tafasitamab plus lenalidomide compared to R-GemOx. Indirect comparisons with other relevant treatment comparators were not conducted, due to infeasibility given the small subgroup.
Patients expressed a need for treatments that prolong survival and remission, control disease symptoms, improve HRQoL, and have fewer side effects compared to current therapies. While acknowledging the need for additional effective treatment options for this patient population, pERC concluded that it is uncertain whether tafasitamab plus lenalidomide meets these important therapeutic needs given the limitations associated with the evidence reviewed.
pERC noted that the subgroup analyses submitted in this resubmission did not address any of the key limitations identified in the previous review, most notably the uncertainty regarding the clinical benefit of tafasitamab plus lenalidomide arising from the noncomparative study design and small sample size. Restricting the evidence to a smaller subgroup without a clear justification or clinical rationale, especially within a post hoc analytical framework further amplifies these limitations and introduces additional methodological concerns and uncertainties in the evidence.
Based on the totality of the clinical evidence, pERC concluded that the clinical value of tafasitamab in combination with lenalidomide in this subgroup of patients remains uncertain. Further information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.
pERC acknowledged that patients identified a need for treatments that prolong survival and remission, control disease symptoms, improve HRQoL, and have fewer side effects than existing therapies. The committee agreed with the clinical experts, clinician, and patient groups in recognizing the need for additional options for this patient population. However, pERC noted that no data were available on the comparative efficacy of tafasitamab plus lenalidomide versus other existing therapies. The primary end point in the L-MIND study was objective response rate (ORR) appeared clinically meaningful. Input from clinical experts confirmed other key end points, PFS and OS, to be more relevant in this setting. In addition, the absence of comparative evidence for ORR and key end points including PFS, OS, HRQoL, and harms limits conclusions regarding the clinical efficacy and safety of tafasitamab plus lenalidomide. pERC further noted that although tafasitamab plus lenalidomide provides a chemotherapy-free treatment alternative for patients with r/r DLBCL, it still poses toxicity risks including myelosuppression and venous thromboembolic events. For patients who are ineligible for ASCT, CAR T-cell therapy, or other intensive regimens due to experiencing frailty or comorbidities, tolerability of any potential treatment option remains an important consideration, and the regimen may not represent an appropriate option for all such patients. Overall, given the uncertainty in clinical value and limited comparative data with other treatment options, pERC could not conclude that tafasitamab plus lenalidomide provides an effective treatment option that meets a unique unmet clinical need in this patient population that is not currently met by other available treatments.
Further information on the committee’s discussion around unmet clinical need is provided in the Summary of Deliberation section.
pERC recognized that there are significant unmet nonclinical needs and health inequities for patients with r/r DLBCL. These include barriers to accessing specialized treatments (e.g., CAR T-cell and bispecific therapies), particularly for patients who are older, experiencing frailty, or living in rural or remote areas, as well as logistical challenges (e.g., travel requirements, caregiver support, and access to infusion centres), which can contribute to inequitable access to treatment and poorer outcomes.
pERC noted the infusion schedule for tafasitamab of 13 infusions during cycles 1 to 3, then biweekly, may be burdensome for patients and may not adequately mitigate existing accessibility inequities or logistical complexities. pERC also noted, based on clinical expert input, that other regimens are available, including treatments that can be administered in community or nontertiary settings. While R-GemOx is not considered the most relevant comparator for all patients and is associated with significant toxicity and administration challenges, another option, pola-BR, is available and, in some cases, a preferable option for patients with r/r DLBCL who are not good candidates for T-cell redirecting therapies and can be administered in community settings. Thus, although tafasitamab plus lenalidomide may help address some access limitations associated with CAR T-cell therapy and bispecific antibody therapy, it does not fully meet all treatment needs given the availability of other therapies with less frequent community-based administration.
pERC concluded that while tafasitamab plus lenalidomide may add to treatment options for patients unable to receive or access intensive or specialized therapies, the degree to which it addresses an unmet nonclinical need is insufficient to outweigh the substantial limitations and uncertainty surrounding its comparative clinical value.
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 to reimburse tafasitamab plus lenalidomide based on clinical value alone. Therefore, they also considered whether tafasitamab plus lenalidomide addressed a significant unmet clinical need with an acceptable level of certainty in clinical value. pERC could not recommend reimbursement even after taking this into account. Finally, they considered whether tafasitamab plus lenalidomide addresses a significant unmet nonclinical need or health inequity. pERC was unable to conclude that tafasitamab plus lenalidomide addresses a significant unmet nonclinical need or health inequity to a degree that overcomes the uncertainty in clinical value and potential risks. Based on all of the preceding considerations, pERC recommended that tafasitamab plus lenalidomide not be reimbursed.
Because pERC recommended that tafasitamab plus lenalidomide not be reimbursed, further deliberation was not required 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.
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.
Efficacy and safety: In this post hoc analysis of a subgroup of the single-arm L-MIND study, ORR by independent review commiitee (IRC) was █████ (95% CI, █████ ██ █████). With a median follow-up of ████ ██████, the median PFS by IRC was ████ ██████ (95% CI, ███ ██████ ██ ████ ██████), the Kaplan-Meier estimate of PFS probability at ██ ██████ was █████ (95% CI, █████ ██ █████). With a median follow-up of ████ ██████, the median OS was ████ ██████ (95% CI, ████ ██████ ██ ████ ██████), the Kaplan-Meier estimate of OS event-free probability at ██ ██████ was ████ | (95% CI, █████ ██ █████). The median duration of response (DOR) by IRC was ███ █████████ (95% CI, ████ ██████ ██ ██), the Kaplan-Meier estimate of DOR event-free probability at ██ ██████ was █████ (95% CI, █████ ██ █████). Overall, no new safety concerns for tafasitamab were identified in the L-MIND subpopulation. pERC concluded that the treatment effects of tafasitamab plus lenalidomide are highly uncertain because the results were derived from post hoc, descriptive analyses without formal hypothesis testing, and are further limited by the substantial uncertainty inherent in the single-arm study design and small sample size.
Clinical importance of treatment effects: Patients identified longer survival and remission, symptoms control, improved HRQoL, 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 clinical expert input, the observed treatment effects of tafasitamab plus lenalidomide on the primary end point of ORR appear clinically meaningful. However, pERC noted expert input indicating that response rate is not the most salient or informative end point for assessing clinical benefit in this setting. PFS, OS, and DOR were secondary end points and due to the absence of a comparator arm, there was no direct evidence to contextualize the magnitude or durability of treatment effects relative to other therapies used in clinical practice.
Certainty of the evidence: For consistency with the initial reimbursement review of tafasitamab and per CDA-AMC resubmission policies, summarized efficacy end points and notable harms were not assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. pERC noted that the certainty of the evidence was very low due to the single-arm design of the L-MIND trial, which limited comparisons with relevant comparators. HRQoL was also not assessed in the L-MIND study. The HRQoL results in the PRO-MIND study were inconclusive because of critical limitations with the methods used in the study and limited generalizability and interpretability of the results in the context of the reimbursement subpopulation in a setting in Canada.
Appropriate comparators: The committee considered pola-BR, R-GemOx, glofit-GemOx, epcoritamab, and glofitamab to be relevant comparators to tafasitamab plus lenalidomide for patients with r/r DLBCL. The committee agreed with the clinical experts consulted by CDA-AMC that CAR T-cell therapy is not considered a relevant comparator because it is an intensive, one-time treatment with curative intent and occupies a distinct clinical niche more comparable to ASCT.
Comparative efficacy and safety: The sponsor-submitted ITCs included comparison of tafasitamab plus lenalidomide only with R-GemOx. The 2 ITCs included an unanchored matching-adjusted indirect comparison and a retrospective real-world comparison from the RE-MIND2 study. pERC considered the unanchored matching-adjusted indirect comparison to be highly uncertain due to incomplete matching on key prognostic factors, limited covariate overlap leading to a reduced effective sample size, residual confounding, and violation of key assumptions, precluding firm conclusions. Although the RE-MIND2 study analysis suggested improved outcomes with tafasitamab plus lenalidomide, differences in study design, population heterogeneity, and outcome definitions introduced potential bias and limited comparability. Overall, pERC concluded that the ITCs with R-GemOx were associated with important methodological limitations and imprecision, resulting in low confidence in the estimates and insufficient evidence to support a difference in efficacy versus R-GemOx. The ITC with R-GemOx did not compare harms. The committee noted the absence of comparative evidence with other treatment options that were included in the previous submission but were deemed infeasible to evaluate within this small subgroup.
Limitations of the evidence in the initial and current submissions: The key limitations identified in the initial recommendation included the single-arm, noncomparative design of the L-MIND study, its small sample size, absence of HRQoL data, and potentially limited generalizability of the trial population to patients in Canada. pERC acknowledged that the sponsor provided additional follow-up (5 years) data, and HRQoL information in the resubmission. However, interpretation of these data remains limited due to the lack of comparator arm which prevents meaningful contextualization of the clinical benefit of tafasitamab plus lenalidomide. The HRQoL evidence, derived from an observational, noncomparative study of ██ patients in Italy, may also have limited applicability to the context in Canada. pERC noted that the key limitations identified in the initial submission persist despite the additional data, and that the resubmission includes a smaller patient population, and fewer ITCs with relevant treatments, further constraining the ability to address the evidentiary uncertainty.
Subgroup for the reimbursement request: pERC raised concerns regarding the sponsor’s revised reimbursement request, which relied on a post hoc defined subgroup that excluded patients with primary refractory disease ███████ those without centrally confirmed DLBCL █████, and ███ ███████ who did not receive treatment █████. pERC noted that further restricting the L-MIND patient population to those without primary refractory disease and with an ECOG PS score of 2 or less, was unnecessary, as these criteria were already embedded in the L-MIND trial eligibility and would naturally apply if a positive reimbursement recommendation were issued. If patients who did not meet key eligibility criteria, such as those with primary refractory disease or without centrally confirmed DLBCL, were inadvertently enrolled, pERC considered that sensitivity analyses to assess the impact of these protocol deviations would have been the appropriate methodological approach. As such, pERC did not view the creation of this subgroup scientifically justified.
Clinical value: Based on the preceding considerations, pERC could not determine whether tafasitamab plus lenalidomide provides clinical value that is at least comparable to current treatment options for the population specified in the reimbursement request, namely adult patients with r/r DLBCL not otherwise specified (including DLBCL arising from low grade lymphoma), excluding primary refractory disease, who are not eligible for ASCT and have an ECOG PS score of 2 or less.
Input on unmet clinical need: Input from the patient group identified a need for treatments that prolong survival and remission, control symptoms, improve HRQoL, and have fewer side effects than existing therapies. Patients, along with clinical experts and clinician groups, highlighted a need for effective and accessible treatment options, particularly for those with r/r DLBCL who are not eligible for CAR T-cell therapy, bispecific antibodies, ASCT, or intensive regimens.
Severity of the disease: DLBCL is the most common subtype of NHL in Canada and is an aggressive and heterogeneous disease that can arise on its own or evolve from other types like follicular lymphoma. The committee considered r/r DLBCL in patients who are ineligible for ASCT to be life-threatening and seriously debilitating, given the poor prognosis, limited treatment options, and shortened survival in this population. Although many patients initially respond to first-line therapy, a substantial proportion have their disease relapse or they develop refractory disease, and outcomes after second-line treatment remain poor, with low long-term survival rates.
Availability of treatment options: Based on input from the clinical experts and clinician groups, available treatments for patients with r/r DLBCL who are not eligible for ASCT include regimens such as R-GemOx, pola-BR, glofit-GemOx, and tafasitamab plus lenalidomide, as well as newer options such as bispecific antibodies (e.g., epcoritamab and glofitamab). While these therapies have expanded the treatment landscape, clinical experts and clinician groups noted that patients who are ineligible for ASCT continue to have limited treatment options, and responses are often not durable. pERC noted that other treatment options are available for patients who are not eligible for ASCT or T-cell redirecting therapies. However, due to the lack of comparative evidence, it remains uncertain how tafasitamab plus lenalidomide compares with these alternatives in terms of efficacy, safety, and HRQoL. pERC also acknowledged that tafasitamab plus lenalidomide offers a chemotherapy-free option for patients with r/r DLBCL who are ineligible for ASCT or T-cell redirecting therapies because they were experiencing frailty or comorbidities. Nonetheless, the toxicity risks associated with this regimen remain important considerations, and it may not represent a clear or appropriate option for all such patients.
Input on unmet nonclinical need: Input from interested parties identified unmet needs related to inequitable access to specialized therapies for patients with r/r DLBCL. Barriers to accessing CAR T-cell and bispecific antibody therapies, along with social, cultural, and logistical challenges such as caregiver support, contribute to disparities in care, particularly for patients who are older or have comorbidities.
Equity considerations: pERC noted that geographic inequities may affect outcomes in patients with r/r DLBCL, with patients living in rural or smaller communities potentially experiencing poorer survival compared with those in urban areas. The clinical experts highlighted that older adults and patients who are immunosuppressed may face greater treatment-related risks, and that these groups were underrepresented in the clinical evidence, contributing to uncertainty about the generalizability of the findings. pERC further noted that the requirement for IV administration may exacerbate inequities due to travel, logistical, and financial burdens, particularly for patients with limited mobility or those living in underserved regions.
Significant unmet nonclinical need or health inequity: pERC discussed several unmet nonclinical needs and health inequities for patients with r/r DLBCL. Experts noted that the disease disproportionately affects underserved and equity-deserving populations, as limited access to specialized centres, long travel requirements, diagnostic delays, and lack of caregiver support can lead to more advanced disease at presentation and poorer outcomes. pERC noted that the dosing schedule for tafasitamab (i.e., weekly during cycles 1 to 3, then biweekly, indefinitely) and IV administration in hospital is likely burdensome for most patients and may not fully address existing accessibility inequities. Input from clinical experts indicated that other regimens are available (e.g., pola-BR), which have less frequent dosing schedules and can be administered in community or nontertiary settings. In particular, pola-BR was noted to be a fixed-duration regimen that can be administered in the community and could be offered to patients ineligible for ASCT or T-cell redirecting therapies. Thus, while tafasitamab plus lenalidomide may address some access barriers to CAR T-cell therapy and bispecific antibody therapy, it does not fully meet treatment nonclinical needs given the treatment intensiveness and availability of less frequently administered community-based options.
Deliberation on social and ethical implications: The committee considered the social and ethical implications of tafasitamab plus lenalidomide; however, the recommendation not to reimburse meant that further deliberation on measures to address these implications was not required.
Deliberation on economic considerations: The committee reviewed the economic considerations for tafasitamab plus lenalidomide; however, the recommendation not to reimburse meant that further deliberation on the considerations was not required.
Deliberation on impacts on health systems: The committee considered the impacts on health systems when implementing tafasitamab plus lenalidomide; however, the recommendation not to reimburse meant that further deliberation on measures to address these impacts was not required.
To make its recommendation, the committee and subcommittee 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 tafasitamab (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 2 clinician groups, Ontario Health (Cancer Care Ontario) Hematology Cancer Drug Advisory Committee and the Ad Hoc Group of Ontario Medical Oncologists and Hematology-Oncologists along with Lymphoma Canada's Scientific Advisory Board (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 DLBCL consulted by CDA-AMC.
Dr. Catherine Moltzan (Chair), Dr. Kelvin Chan (Vice-Chair), Paul Agbulu, Dr. Phillip Blanchette, Dr. Matthew Cheung, Annette Cyr, Dr. Jennifer Fishman, Dr. Prafull Ghatage, 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: June 10, 2026
Regrets: Two expert committee members did not attend.
Conflicts of interest: None
ISSN: 2563-6596
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