Oral azacitidine for maintenance treatment of acute myeloid leukaemia after induction therapy

People with acute myeloid leukaemia would welcome a new treatment option

3.1 Acute myeloid leukaemia (AML) is a rapidly progressing cancer of the blood and bone marrow that is usually diagnosed in older people. Treatment options for AML include chemotherapy and a stem cell transplant (see section 3.2). The committee understood the substantial psychological, social and physical impact of living with AML for people with the condition their carers and families. The patient expert described how being diagnosed with AML and the potential prospect of living for only a few months, had a significant emotional impact on them and their family. The clinical experts explained how intensive chemotherapy is associated with morbidity and that each treatment cycle often requires a prolonged hospital stay over several weeks. They explained that because a person's immune system is likely to weaken with chemotherapy, this increases their likelihood of contracting a life-threatening infection, which is an additional worry for people having treatment. The clinical experts explained that for people who are well enough to have intensive chemotherapy, a transplant remains the most effective treatment option. The committee understood that the decision to have a transplant depends on a person's fitness, choice, response to chemotherapy, and donor availability. The clinical experts highlighted that most people with AML are aged over 60 and are often unable to have a transplant because of co-morbidities and frailty. They also explained that there is a lack of donor availability for people from ethnic minority groups. Therefore, some people cannot have, or do not want to have a stem cell transplant. The clinical experts explained that the risk of relapse in people who do not have a transplant is around 70% to 80%. They added that this would most likely occur within the first year after reaching complete remission. They highlighted that there are no effective treatment options after relapse in this population and that their prognosis and quality of life is poor. The committee noted that while stem cell transplants have the potential to be curative, they are associated with significant morbidity and mortality. The patient expert described how their treatment in preparation for a stem cell transplant was painful and invasive and made them feel too unwell to carry out their regular activities. The committee heard how the financial implications of having a transplant, such as regular travel to hospital and having to take time off work, can have a significant impact on quality of life for people with AML, their carers and families. It understood that oral azacitidine would benefit people who cannot have, or do not want to have a stem cell transplant because it can be taken at home. The committee concluded that people with AML would welcome a new treatment option that would improve their survival and quality of life.

Low dose cytarabine and subcutaneous azacitidine are not routinely used for maintenance treatment

3.2 Treatment for AML depends on whether a person is able to have intensive chemotherapy. If intensive chemotherapy is unsuitable, low dose chemotherapy may be given. If intensive chemotherapy is suitable, induction chemotherapy is initially given to achieve complete remission followed by consolidation chemotherapy. After induction or consolidation chemotherapy, some people may be able to have a stem cell transplant. People who are diagnosed with FLT3-mutation-positive AML may also have concomitant treatment with midostaurin during induction and consolidation chemotherapy and continue with midostaurin alone as maintenance treatment to prolong their remission (see NICE's technology appraisal guidance on midostaurin for untreated acute myeloid leukaemia). The committee discussed the company's positioning of oral azacitidine as a maintenance treatment for people who are in complete remission after induction chemotherapy, with or without consolidation chemotherapy, and who are not able to have a stem cell transplant. The final scope for this appraisal included established clinical management without oral azacitidine (which may include a watch and wait strategy with best supportive care, low dose cytarabine or subcutaneous azacitidine) as a comparator. The committee noted that the company had not included low dose cytarabine and subcutaneous azacitidine as part of established clinical management. The company's clinical experts considered that these treatments are not used as maintenance treatment in the population eligible for oral azacitidine. The committee discussed the stakeholder comments that low dose cytarabine and subcutaneous azacitidine are not used routinely after induction and consolidation chemotherapy but are used when intensive chemotherapy is unsuitable. It noted the company's response to technical engagement which referenced data from the Haematological Malignancy Research Network (HMRN), which is an ongoing UK population-based cohort. The company presented subgroup data from the HMRN which was aligned to the eligibility criteria of the key clinical trial of oral azacitidine (see section 3.4). This indicated that very few people had maintenance treatment with low dose cytarabine and subcutaneous azacitidine (actual figures are confidential and cannot be reported here). Therefore, the committee concluded that these treatments would not likely be used routinely as maintenance treatment in people who are in complete remission.

Midostaurin is a relevant comparator for people with FLT3-mutation-positive AML

3.3 The committee noted that the company's clinical experts considered that around 25% of people with AML have FLT3-mutation-positive AML. Most of these people will have a stem cell transplant after reaching remission, leaving around 10% who would likely have maintenance therapy with midostaurin. The clinical experts explained that most people with FLT3-mutation positive AML would have targeted treatment with midostaurin during induction, consolidation and maintenance treatment and would be unlikely to switch to oral azacitidine. The committee heard how midostaurin is often not well tolerated, so having an alternative treatment option such as oral azacitidine would be important for this population. It recognised that the proportion of people with FLT3-mutation-positive AML who would have oral azacitidine in clinical practice would likely be small, but that it was still a relevant population. Therefore, the committee concluded that midostaurin was a relevant comparator for people with FLT3-mutation-positive AML.

Oral azacitidine improves overall survival and relapse-free survival compared with placebo

3.4 The clinical evidence came from QUAZAR AML-001 (from now, referred to as QUAZAR), a phase 3, double-blind, randomised controlled trial that compared oral azacitidine plus best supportive care (from now, referred to as oral azacitidine) to placebo plus best supportive care (from now, referred to as placebo). The company considered that the placebo arm represented the watch and wait comparator. The population included adults with AML in complete remission after intensive induction chemotherapy with or without consolidation chemotherapy, who were not able to have a stem cell transplant. The company reported data from the trial's first data cut (July 2019, median follow up 41.2 months) for all outcomes. It also reported data from a second data cut (September 2020, median follow up 51.7 months) for the primary outcome of overall survival. In the intention to treat (ITT) population, oral azacitidine increased median overall survival compared with placebo from 14.8 months to 24.7 months (hazard ratio 0.69; 95% confidence interval 0.56 to 0.86, p value 0.0008). In the ITT population, oral azacitidine increased median relapse-free survival compared with placebo from 4.8 months to 10.2 months (hazard ratio 0.65; 95% confidence interval 0.52 to 0.81, p value 0.0001). The committee welcomed the mature trial data from QUAZAR and concluded that oral azacitidine improves overall survival and relapse-free survival compared with placebo.

The trial results from the EU-subgroup are generalisable to clinical practice in England and should be used for decision-making

3.5 The QUAZAR trial included 148 sites and included a large number of European people (known as the EU-subgroup) and a small number of people from the UK (the actual numbers are considered confidential by the company and cannot be reported here). The EU-subgroup was part of the company's pre-specified subgroup analyses. The company considered that the baseline characteristics of people in QUAZAR aligned to the AML population in the UK who cannot have a transplant, with some exceptions:

The clinical experts explained that the treatment pathway for younger people would be the same as for those aged over 55 years. They explained that because of the toxicity associated with intensive chemotherapy, many younger people are also unable to have a transplant because they are not well enough or do not have a suitable donor. The ERG highlighted differences between the UK population and the European and ITT populations including the proportion of people who were unable to have a stem cell transplant because of not having an appropriate donor. The ERG also noted that there were some inconsistencies between the number of pre-trial consolidation cycles observed in the UK population and the company's clinical expert estimates of consolidation therapy use in people with AML who are not able to have a transplant. Because of these differences, and because only a small number of people from the UK were included in the trial, the ERG considered that the EU-subgroup may be more relevant to UK clinical practice. In response to technical engagement, the company revised its base case to use data for the EU-subgroup (rather than the original ITT population) which reduced the incremental cost-effectiveness ratio (ICER). The company highlighted that the baseline characteristics of the subgroup from the HMRN report (aligned to the QUAZAR trial eligibility criteria) were in line with the EU-subgroup. The committee noted that stakeholders had commented that the QUAZAR trial was generally representative of UK clinical practice. The clinical experts considered that there was no strong evidence to suggest that the UK subgroup in the trial was not representative of the UK population, but they noted that the numbers in this subgroup were small. They explained that the QUAZAR study included European people, and that the baseline characteristics for this subgroup reflected the population who would have oral azacitidine in the NHS. The committee concluded that the trial results from the EU-subgroup were generalisable to clinical practice in England and should be used for decision-making.

The number of cycles of pre-trial consolidation therapy in QUAZAR likely reflects NHS clinical practice

3.6 The ERG noted that in QUAZAR, most people had 1 or no cycles of pre-trial consolidation therapy. The committee understood that 20% of people in the trial did not have any pre-trial consolidation therapy (based on the ITT population). The ERG considered that previous NICE technology appraisals for untreated AML imply that consolidation therapy is standard practice, but the number of cycles of consolidation is unclear. In response to technical engagement, the company's clinical experts suggested that there is variability in the number of consolidation cycles and that up to 60% of people in the UK are likely to have only 1 or no cycles in routine practice. The company presented data from the HMRN report which highlighted that in the NHS, a proportion of people whose cancer responded to intensive induction therapy did not have any cycles of consolidation chemotherapy (actual numbers are confidential and cannot be reported here). The ERG considered that there is some disparity between the HMRN report findings and the NHS website which suggest that all people with AML have consolidation therapy. It noted that the European Society for Medical Oncology's (ESMO) clinical practice guideline on acute myeloid leukaemia in adult patients (2020) recommends that people should have consolidation therapy after reaching complete remission following induction treatment. The ERG considered that consolidation therapy is expected so it preferred to use a subpopulation of the EU-subgroup who had had at least 1 cycle of consolidation therapy for its base case. This subpopulation was known as the EU-consolidation subgroup. The committee noted that the EU-consolidation subgroup slightly increased the ICER. The clinical experts explained that in clinical practice, many people can only have a single course of consolidation chemotherapy, because of delayed blood count recovery, toxicity, patient choice or clinician decision. They described how optimum best practice includes 3 to 4 cycles of consolidation chemotherapy, however this is difficult to achieve particularly in the older population. The clinical expert described that around 20% of people will have the optimum number of consolidation cycles. They explained that the QUAZAR trial reflects the use of consolidation chemotherapy in clinical practice. The committee noted that data from the trial suggested that overall survival was improved irrespective of whether a person had consolidation treatment. The committee concluded that although most people would likely have at least 1 cycle of consolidation therapy, there may be people who would not have any consolidation treatment after induction chemotherapy. It concluded that the number of cycles of pre-trial consolidation therapy in QUAZAR likely reflect NHS clinical practice.

The results of the company's indirect treatment comparison in people with FLT3-mutation-positive AML are highly uncertain

3.7 The company did not identify any direct evidence comparing the efficacy of oral azacitidine to midostaurin as maintenance treatment in people with FLT3-mutation-positive AML. Therefore, it did an anchored indirect treatment comparison using data from QUAZAR and a phase 3, randomised, placebo-controlled study of midostaurin plus standard chemotherapy in adults with newly diagnosed FLT3-mutation-positive AML (known as RATIFY). Because individual person data was available from QUAZAR, the company matched the population in QUAZAR to the eligibility criteria in RATIFY, so that only people with a FLT3-mutation in complete remission were included in the analysis. The company considers the results of the indirect treatment comparison to be confidential and so these cannot be reported here. However, the company noted significant differences between QUAZAR and RATIFY including:

The company considered that many of these variables are known prognostic factors and potential effect modifiers and so the indirect estimates of oral azacitidine and midostaurin are likely limited in their validity and generalisability. The ERG also considered that survival analyses for this population are likely to be biased because of limitations associated with the indirect treatment comparison. It concluded that the results of the indirect treatment comparison comparing oral azacitidine with midostaurin were highly uncertain and considered this in its decision making.

It is uncertain whether the company's model captures the long-term benefit after a stem cell transplant

3.8 The company presented a partitioned survival model with 3 health states: relapse-free survival, relapse, and death. In the relapse-free health state, people could either be on or off treatment with oral azacitidine (the same utility value was applied). All people in the watch and wait plus best supportive care arm (from now, referred to as best supportive care), were assumed to be off treatment. The model included a cycle length of 28 days with a half-cycle correction over a lifetime time horizon. In the model, stem cell transplant was not included as a separate health state but was implicitly included in the modelling through the survival analysis of the QUAZAR ITT population. The company considered that because oral azacitidine has a marketing authorisation for people who are not suitable for a transplant, it would be unlikely in clinical practice that people will go on to have a transplant after oral azacitidine unless they had relapsed. In the trial, 6.3% of people in the oral azacitidine arm and 13.7% in the placebo arm had a transplant after stopping treatment. Costs and a temporary disutility associated with stem cell transplant were included in the model. The committee noted that the ERG's preference was to include stem cell transplant as a health state in the model. In response to technical engagement, the company stated that the QUAZAR trial did not collect sufficient data to allow modelling of stem cell transplant as a separate health state and this data is not available in the literature. Instead, it provided a scenario analysis which calculated a weighted average utility value for each treatment arm in the relapse health state. This was to account for the potential long-term health-related quality-of-life benefits of a transplant. The committee noted that the company's scenario analysis suggested only a small impact on the ICER. The ERG considered that it was unclear whether the model captured the long-term benefits of a stem cell transplant on a person's health-related quality of life (including following the company's scenario analysis). The committee agreed with the ERG's preference to remove the temporary disutility associated with a transplant, given that no benefit in health-related quality of life after having a transplant had been included in the model. It noted that the removal of this disutility had a small impact on the ICER. The committee considered the ERG's scenario analysis which included a utility increment for people who went on to have a stem cell transplant and noted that this slightly increased the ICER. The committee considered that it would have preferred the company to have included stem cell transplant as a health state in the model in line with NICE's technology appraisal guidance on midostaurin for untreated acute myeloid leukaemia. It concluded that it is uncertain whether the company's model captures the long-term benefits after a stem cell transplant.

Health-related quality of life after relapse should be calculated using data from Tremblay 2018

3.9 The company considered that the QUAZAR trial did not capture health-related quality of life after relapse, except in some people who may have received an extended dose of oral azacitidine. This included people with a bone marrow blast count of 6% to 15% but not those with advanced disease (blast count greater than 15%). The company considered that using a utility value derived from this small cohort of people would be inappropriate and may overestimate the quality of life for people who relapse. Therefore, the company calculated the relapse utility based on a study by Joshi 2019 which used the composite time trade-off method to elicit utility values for AML from the UK general population. In the model, relapse utility was calculated as the difference between the relapse-free survival and relapse utilities in Joshi 2019 which was then applied to the relapse-free utility from QUAZAR. The ERG noted that the sample size in Joshi 2019 was small which resulted in a large standard error. The committee understood that the company considered alternative sources for relapse utilities including studies by Stein 2019 and Tremblay 2018. The ERG considered that both sources were not ideal because utility values were derived from US populations. In response to technical engagement, the company explained why the study by Joshi 2019 had been selected. It considered the utility elicitation methodology to be preferred by NICE, utility values were from individuals in the UK, and the utility value was clinically plausible. The ERG was unclear why the company preferred the composite time trade-off methodology given that it was not part of the reference case in NICE's guide to the methods of technology appraisal 2013. In line with NICE's technology appraisal guidance on midostaurin for untreated acute myeloid leukaemia, the ERG used Tremblay 2018 to calculate health-related quality of life after relapse. in its base case. This was because it considered that the method used to elicit utility values was more appropriate than Joshi 2019. The committee noted the company's scenario analyses using relapse utility values from Tremblay 2018 and Stein 2019 had a small impact on the ICER. It agreed with the ERG's approach and concluded that health-related quality of life after relapse should be calculated using data from Tremblay 2018.

Utility for the relapse-free survival health state should be capped at age and sex matched general population values

3.10 The committee understood that the company had adjusted health state utility values for age in the model. It discussed the ERG's critique that the relapse-free survival utility was higher than the age-adjusted population norm in the UK. The committee considered that this did not make sense because it would mean that people with AML had a better quality of life than people without the disease. It noted that the ERG had asked the company to provide a scenario analysis capping the utility at general population levels which slightly increased the ICER. The committee concluded that the utility value for the relapse-free survival health state in the model should be capped at age and sex matched general population levels.

There is uncertainty around the extrapolation of overall survival which may overestimate the expected treatment benefit with oral azacitidine

3.11 To extrapolate beyond the QUAZAR trial data, the company used joint models (joint models apply a single distribution to both treatment arms) to estimate overall survival. It used the generalised gamma acceleration time failure model for overall survival and the log-logistic acceleration time failure model for relapse-free survival in the ITT population. The company considered that the survival analyses in the EU-subgroup were aligned with the assessment for the ITT population. The committee considered that the joint modelled curves showed that the survival function was being underestimated in the model for the comparator arm (best supportive care) when compared to the Kaplan-Meier curves from the trial. It considered that this may be because acceleration failure time models assume that the treatment effect is constant over the entire lifetime of the model. The committee noted that the ERG conducted a scenario which explored the impact of using individual parametric models for the EU-consolidation subgroup. In this scenario, for overall survival the ERG selected the generalised gamma model for both arms. For relapse-free survival, the log-logistic model was selected for both arms. The committee noted that the results with the ERG's base case assumptions slightly reduced the ICER. The company explained that it had assumed no treatment effect waning for oral azacitidine in its base case analysis. The committee considered that it was highly optimistic to assume a constant treatment benefit with oral azacitidine based on the observed trial data. The committee understood that the company had presented a scenario analysis which tried to explore the impact of treatment effect waning by using individual log-normal models for overall survival and log-logistic models for relapse-free survival. The results of the scenario analysis increased the ICER by 11%. The committee considered that this was not explored fully and it would be preferable to include an assumption that the relative treatment effectiveness would decline over time. Therefore, the committee considered that it would be helpful to see a range of scenarios for both the overall population (based on the EU-subgroup) and for people with FLT3-mutation-positive AML including:

The committee considered that without these analyses, it was unclear what impact the scenarios would have on the cost-effectiveness results, but that they were likely to increase the ICER. It concluded that there was uncertainty around the company's extrapolation of overall survival and that this may overestimate the expected treatment benefit with oral azacitidine.

Oral azacitidine extends life by at least 3 months

3.12 The committee considered the advice about life-extending treatments for people with a short life expectancy in NICE's guide to the methods of technology appraisal 2013. The committee agreed that based on the trial evidence and the views of clinical experts, the overall survival gain with oral azacitidine would likely be more than 3 months. The company's model suggested that there was an increase in mean overall survival of 12.8 months (median 9.9 months) for the ITT population. For the EU-subgroup, the company's model suggested that there was an increase in mean overall survival of 16.2 months (median overall survival gain was greater than 3 months but the exact figure is confidential so cannot be reported here). The committee agreed that oral azacitidine meets the criterion for a life-extending treatment because it increases overall survival by more than 3 months.

The short life expectancy criterion has not been met so oral azacitidine is not considered to be a life-extending treatment at the end of life

3.13 The company confirmed that mean estimates were not available from QUAZAR, but the median overall survival for people who had placebo was 14.8 months (ITT population). The company's original base case for the ITT population predicted a mean overall survival of 33.6 months for people having best supportive care. The company's revised base case using the EU-subgroup predicted a mean overall survival of 31.5 months for people having best supportive care. The committee acknowledged that using extrapolation models to estimate mean values involves assumptions and uncertainty. However, the committee noted that the mean estimates were significantly higher than 24 months and that the cost-effectiveness analyses are based on mean survival estimates. The clinical experts explained that a significant number of people with AML are unable to have a stem cell transplant and in these people the risk of relapse is significant in the first year. After relapse, these people would have palliative treatment within 12 months and a life expectancy of around 3 months at this point. They explained that there will be a proportion of people around 20%, who may be cured after intensive chemotherapy and reach long term survival. The ERG considered that because some people will live for much longer, this will skew the survival distribution where the mean is often higher than the median. The committee discussed that the mean overall survival estimates from the model were discounted results and that the undiscounted results were higher (38.9 months in the ITT population and 36.5 months in the EU-subgroup for people having best supportive care). It recalled that while the short-term prognosis for most people would be poor, a proportion of people (around 20%) would be cured and would therefore be expected to live beyond 2 years. Therefore, the committee concluded that the short life expectancy criterion had not been met and that oral azacitidine could not be considered a life-extending treatment at the end of life.

Oral azacitidine is not cost effective compared with best supportive care

3.14 NICE's guide to the methods of technology appraisal notes that above a most plausible ICER of £20,000 per quality-adjusted life year (QALY) gained, judgements about the acceptability of a technology as an effective use of NHS resources will take into account the degree of certainty around the ICER. The committee will be more cautious about recommending a technology if it is less certain about the ICERs presented.

The committee considered that there was uncertainty around some of the assumptions used in the model and that this makes the cost-effectiveness results uncertain. The committee was willing to be flexible despite these uncertainties if it could potentially address the equality issues raised by stakeholders (see section 3.17). It considered that scenario analyses which explored the use of individual parametric models for extrapolating overall survival and treatment effect waning would reduce the uncertainty that the expected treatment benefit with oral azacitidine had been overestimated in the model (see section 3.11). These analyses would form part of the committee's preferred assumptions if they could be done robustly. In the absence of these analyses the committee's remaining preferred assumptions included:

The committee's preferred deterministic and probabilistic ICERs for oral azacitidine compared with best supportive care, were above £30,000 per QALY gained. Exact ICERs are confidential and cannot be reported here, because they include the confidential patient access scheme for oral azacitidine and confidential comparator discounts. The committee noted that it did not have analyses that included its preferences around the modelling of overall survival and duration of treatment benefit with oral azacitidine. It considered it was likely that such analyses would increase the ICER further. The committee considered that the most plausible ICER would be above the range that NICE considers to be an acceptable use of NHS resources. Therefore, it could not recommend oral azacitidine as an option for people with AML.

Oral azacitidine is not recommended for people with FLT3-mutation-positive AML

3.15 The committee noted the ICERs for all the scenarios presented for oral azacitidine compared with best supportive care and for oral azacitidine compared with midostaurin for the FLT3 subgroup. All the ICERs were within the range that NICE considers to be an acceptable use of NHS resources (including the confidential patient access scheme for oral azacitidine and confidential comparator discounts). It noted that the cost-effectiveness estimates for oral azacitidine compared with midostaurin were highly uncertain because of the limitations in the clinical evidence informing this treatment comparison (see section 3.7). The committee recalled that the proportion of people with FLT3-mutation-positive AML who would have oral azacitidine in clinical practice would be small. It considered that an optimised recommendation for oral azacitidine in this population would not benefit most people with AML. Therefore, the committee concluded that it would only consider recommendations for oral azacitidine in all people with AML and that it would not make an optimised recommendation for people with FLT3-mutation-positive AML.

Oral azacitidine does not meet the criteria to be included in the Cancer Drugs Fund

3.16 Having concluded that oral azacitidine could not be recommended for routine use, the committee considered if it could be recommended within the Cancer Drugs Fund. It discussed the new arrangements for the Cancer Drugs Fund agreed by NICE and NHS England in 2016, noting NICE's Cancer Drugs Fund technology appraisal process and methods guide (addendum). The committee considered that the data from the QUAZAR trial was mature and that it was unlikely that further data collection would address the uncertainties identified. It concluded that oral azacitidine did not meet the criteria for inclusion in the Cancer Drugs Fund.

The equality issues cannot be addressed in the appraisal because oral azacitidine is not recommended for people with AML

3.17 The committee discussed the potential equality issues raised during the appraisal. It noted comments from stakeholders that many people with AML who are in complete remission are unable to have a transplant because of a lack of donor availability. Therefore, this results in an inequity of access to curative treatment and disproportionately affects people from ethnic minority groups. The clinical experts explained that after a transplant there is a 70% reduction in the risk of relapse. They explained that in people of white ethnicity, the likelihood of finding a suitably matched donor is around 80%, which reduces to around 30% to 40% in people from ethnic minority groups. Stakeholders and clinical experts highlighted that oral azacitidine should therefore be available to all people who are not able to have a transplant, including those from ethnic minority groups who do not have a suitable donor. It noted a stakeholder comment that some people may struggle financially to have current treatment because of the cost of regular travel to hospital and reduced income from having to take time off work. Having a transplant may be especially difficult for people with caring responsibilities because of the significant time commitment needed. The stakeholder considered that these people should not be denied treatment and oral azacitidine would be a viable alternative to a transplant. The committee acknowledged that these issues are important considerations and it was mindful of its obligations in relation to the Equality Act 2010. It accepted that oral azacitidine would be a welcome option and could reduce these potential equality issues. However, because of the uncertainties in the cost-effectiveness results, the committee concluded that these would need to be addressed before it could recommend oral azacitidine for people with AML.

The benefits of oral azacitidine are captured in the cost-effectiveness analysis

3.18 The company and stakeholders considered oral azacitidine to be innovative because it improves survival, is well tolerated and because of its oral formulation. The committee recalled how treatment with oral azacitidine would offer benefits because people would be able to have treatment at home (see section 3.1). It heard how this would reduce time spent in hospital and allow people to spend more time with their family and friends. The committee agreed that these are important benefits and noted that oral azacitidine is the first maintenance treatment licensed for all people with AML. However, it concluded that it had not been presented with evidence of any additional benefits that could not be captured in the QALY.