e19512 Background: Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies. Recently, a randomized, open label study among previously untreated, chemotherapy-ineligible AML patients demonstrated improved overall survival (OS) among patients treated with glasdegib (GLAS) + LDAC compared with LDAC alone. Two trials of AZA vs. conventional care regimens report data by bone marrow blast (BMB) counts: one with 20-30% and the other with >30%. In the absence of head-to-head comparisons, this study aims to perform the indirect treatment comparison between GLAS+LDAC and AZA by BMB counts. Methods: As there were potential imbalances between the GLAS and AZA trials and within the AZA trial arms in the baseline characteristics (e.g. poor cytogenetics% and de novo%), simulated treatment comparisons (STCs) for GLAS+LDAC vs. LDAC were performed to derive robust estimation by adjusting for the imbalances in the baseline effect modifiers. Afterwards, the classical network meta-analysis (NMA) was conducted. To derive the hazard ratio (HR) of GLAS+LDAC vs. AZA, three NMAs were conducted in each BMB group. Each NMA used a different HR of GLAS+LDAC vs. LDAC: 1) an unadjusted HR (classical NMA), 2) an STC adjusted HR adjusting for potential imbalances between the trials, and 3) an STC adjusted HR additionally accounting for potential imbalances between arms within the AZA trial. Results: In the 20-30% BMB group (N = 30), the OS HRs of GLAS+LDAC vs. AZA resulting from the three respective NMAs were as follows: 1) 0.46 [95% confidence interval: 0.10-2.14], 2) 0.31 [0.06-1.69], and 3) 0.36 [0.06-2.15]. In the > 30% BMB group (N = 80), the HRs were 1) 0.69 [0.39-1.20], 2) 0.48 [0.23-0.97], and 3) 0.48 [0.24-1.00]. All the HRs suggest that patients with GLAS+LDAC have a survival advantage over patients with AZA. Conclusions: Both the classical NMAs and the NMAs based on the STC adjusted HRs correcting for the potential imbalances at baseline suggest that GLAS+LDAC may be preferred over AZA as a treatment option for previously untreated chemotherapy-ineligible AML patients regardless of BMB counts. [Table: see text]
Aim: The clinical efficacy and safety of DAURISMO (glasdegib) combined with low-dose cytarabine (LDAC) were demonstrated in the BRIGHT AML 1003 study among newly diagnosed acute myeloid leukemia patients who are not eligible to receive intensive chemotherapy. This study aims to evaluate its cost-effectiveness versus LDAC alone and azacitidine from a Canadian payer perspective. Materials and Methods: A partitioned-survival model was developed with three health states: progression-free survival (PFS), relapse/progression and death. Clinical inputs were obtained from the BRIGHT AML 1003 study for glasdegib and LDAC, and from the two trial publications and indirect treatment comparison for azacitidine. Drug acquisition/administration, disease management, adverse event and end-of-life costs were considered. All costs were measured in Canadian dollars. Cost-effectiveness of glasdegib þ LDAC was assessed against LDAC alone in main population, and against azacitidine by bone marrow blasts (BMB). A weighted average ICER was calculated to represent the current treatment use of Canadian clinical practice. The reference-case analysis was conducted probabilistically, and numerous probabilistic scenario analyses were conducted. Results: The incremental cost-effectiveness ratios (ICERs) compared to LDAC alone was CAD $177,065 (a mean gain of 0.41 QALYs and an incremental cost of CAD $72,695), to azacitidine in 20-30% and >30% BMB group were CAD $178,201 (a mean gain of 0.34 QALYs and an incremental cost of CAD $59,889) and dominant (a mean gain of 0.28 QALYs while reducing costs by CAD $7,856) respectively, resulting in a weighted average ICER of CAD $81,310 per QALY. Limitations and conclusions: Though uncertainties remain with the generated PFS curve, the derived azacitidine curves, administration and vial wastage, the model has been built under the best available evidence and relied on clinical opinions where there were data gaps. The weighted average ICER suggests that glasdegib þ LDAC is cost-effective at a CAD $100,000 willingness-to-pay threshold.
Introduction Acute myeloid leukemia (AML) is an orphan disease with one of the lowest five-year survival rates among myeloid malignancies in United States adults. Older AML patients face a much lower 5-year survival rate than their younger counterparts (8% for those aged 60-65 years vs. 38% for those under 45 years). Current therapies are limited and historically include low-dose cytarabine (LDAC), decitabine, azacitidine (AZA) and best supportive care. A phase II randomized study (Cortes et al, 2019) among previously untreated AML patients who are not eligible for intensive chemotherapy demonstrated improved overall survival (OS) in patients treated with glasdegib (GLAS) in combination with low-dose cytarabine (LDAC) compared to patients receiving LDAC alone. There are two trials comparing AZA with conventional care regimens that report data by bone marrow blasts (BMB) count: Fenaux et al. (2010) for patients with 20-30% BMB and Dombret et al (2015) for patients with over 30% BMB. In clinical practice, AZA may be restricted to the 20-30% BMB population, which is important to consider when comparing treatment options. Therefore, as there are currently no head-to-head comparisons for GLAS+LDAC vs AZA, two separate indirect treatment comparisons (ITCs) were performed in different BMB populations (i.e., 20-30% and >30% BMB). ITCs is an accepted method to support evidence-based comparative effectiveness decision making and ultimately help to optimize treatment and outcomes of patients with previously untreated AML. Method ITCs were conducted in a classical frequentist statistical framework based on the Bucher method. Patient-level data of the Cortes study (data-cut: January 2017) was divided into two subgroups in terms of BMBs, 20-30% (n=30) and >30% (n=80) to match the patient population of Fenaux et al (n=34) and Dombret et al (n=399) accordingly. GLAS+LDAC and AZA were compared in terms of overall survival and results were reported in terms of hazard ratio (HR) with corresponding 95% confidence intervals (95% CI). AZA was chosen as the reference treatment in the ITC. Results In the 20-30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.46 (95% CI: 0.10-2.14). In the >30% BMB population, the estimated OS HR of GLAS-LDAC in comparison to AZA was 0.61 (95% CI: 0.35-1.08). Conclusion These ITCs suggest that GLAS+LDAC is trending towards being a better treatment option for improving OS in patients with AML compared with AZA, irrespective of the level BMB. These results are consistent with previously published ITC results for this treatment comparison. The results of this ITC should, however, be interpreted with caution due to methodological limitations. First, the relatively small number of patients and deaths result in high uncertainty (as exemplified by the 95% CIs) and, second, patient baseline characteristics (including cytogenetic risk, ECOG status and de novo status) between trial arms and over the different trials were either imbalanced or not reported. While more research is needed, current evidence suggests that GLAS+LDAC may be the preferred treatment option for previously untreated AML patients irrespective of BMB levels. Disclosures Van Beekhuizen: Ingress-health: Consultancy, Other: funding from Pfizer. Bell:Pfizer Inc.: Employment, Equity Ownership. Gezin:Ingress-health: Consultancy, Other: funding from Pfizer. Cappelleri:Pfizer: Employment, Equity Ownership. Heeg:Ingress-Health: Employment. Selya-Hammer:Pfizer Inc: Employment, Equity Ownership. Charaan:Pfizer Inc: Employment, Equity Ownership. Chan:Pfizer Inc: Employment, Equity Ownership.
Introduction: Acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML) are both hematological malignancies characterized by rapid onset. While AML is more common than ALL, both typically receive cytotoxic chemotherapy in first line. Upon complete remission, patients will be considered for allogeneic hematopoietic stem cell transplant (HSCT). The economic burden of malignant blood disorders was recently studied in Europe, with an estimated €3.6 billion in productivity losses. The objective of this review is to evaluate the impact on productivity and understand the societal burden of HSCT in ALL and AML patients. Methods: A rapid review was conducted to identify real-world evidence reporting work and productivity loss associated with ALL and AML, including the impact of HSCT. A search of PubMed was executed for citations published between April 1, 2014 to April 1, 2019 and limited to English language. Eligible studies examined outcomes on work productivity in patients diagnosed with ALL, AML, or combined hematological malignancies, with no geographical restriction. A single reviewer screened all identified citations and extracted key data from included papers. Results: A total of 13 unique real-world data studies were identified. Seven studies examined the impact of hematological cancers (including ALL and AML) with varied return-to-work outcomes reported. Of these, 3 studies observed positive return-to-work outcomes over time, while 4 reported decreased employment among patients when compared to the general population, although 2 of the 4 studies were focused on childhood hematological cancer survivors. A total of 6 studies examined the impact of HSCT on work productivity. Two studies reported opposing results in unemployment in adult survivors of childhood hematological cancers who received HSCT. The remaining 4 studies found a general decrease in employment or increase in low-income status among adult patients when comparing pre-HSCT to post-HSCT; however, 2 of these studies reported most patients were still employed post-HSCT, with 62% returning to work over 1 year post-HSCT and 77% of patients returning to work 5 years post-HSCT. Overall, there was a trend towards work reintroduction as an important outcome post-HSCT. Further, recurring themes included structural changes in the current delivery of health services or potential interventions to help rehabilitation post-transplantation and optimize employment. Conclusions: Work productivity outcomes are important facets of long-term survivorship care in patients with hematological cancers. Although there was a limited number of studies identified, results from the current rapid review indicate that while productivity is lower in patients with AML or ALL, including those treated with HSCT, a substantial proportion of patients are still actively employed. Future research should be directed toward understanding the causes of unemployment post-HSCT to help prevent adverse financial outcomes following this life-saving procedure. In terms of limitations, none of the identified studies compared work productivity outcomes of those who received HSCT to those who did not receive HSCT, among patients with hematological cancer. Four of the studies only examined patients pre- and post-HSCT and the remaining 2 studies compared patients to the general population; thus, the effect of HSCT could not be discerned from the effect of the disease. While HSCT is a costly and resource-intensive procedure, it remains the only potentially curative intervention for most hematological cancers. Advances in HSCT have dramatically improved clinical outcomes in cancer patients; resulting in lowered HSCT-related morbidity and mortality. Future studies with direct comparisons of patients with hematological cancer who received HSCT to those who did not receive HSCT would be desirable to estimate the indirect costs of impact of work productivity in these patients; however, ability to receive HSCT may remain confounded by variables that are challenging to measure, such as disease state, donor availability, HSCT reimbursement policies, and patient preference. Disclosures Scory: Medlior Health Outcomes Research: Employment. Shaw:Medlior Health Outcomes Research: Employment. Cowling:Medlior Health Outcomes Research: Employment. Peloquin:Pfizer Inc: Employment, Equity Ownership. Welch:Pfizer Inc: Employment, Equity Ownership. Charaan:Pfizer Inc: Employment, Equity Ownership. Brown:Pfizer: Employment, Equity Ownership.
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