Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia

Patel, Kishan; Zeidan, Amer M.; Shallis, Rory M.; Prébet, Thomas; Podoltsev, Nikolai A.; Huntington, Scott F.

doi:10.1182/bloodadvances.2020003902

Cited by 26 publications

(21 citation statements)

References 42 publications

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“…Conversely, in AML subtypes clearly benefitting from the combination treatment compared to HMA alone, such as NPM1-or IDH-mutated cases [141,149,262], we would generally favor the combinations, despite the risks. Finally, questions have been raised concerning the cost effectiveness of azacitidine and venetoclax when considering the whole population of unfit AML patients, a further reason to carefully select patients who can benefit the most from the combination of treatment, especially in public health systems [263]. Patients below 65 years are very often treated as younger ones and can be frequently offered the same clinical trials, usually with dose reductions (e.g., cytarabine dose < 1-1.5 g/m 2 ).…”

Section: Discussionmentioning

confidence: 99%

Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021

Urbino

Secreto

Olivi

et al. 2021

Cancers

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Acute myeloid leukemia (AML) in older patients is characterized by unfavorable prognosis due to adverse disease features and a high rate of treatment-related complications. Classical therapeutic options range from intensive chemotherapy in fit patients, potentially followed by allogeneic hematopoietic cell transplantation (allo-HCT), to hypomethylating agents or palliative care alone for unfit/frail ones. In the era of precision medicine, the treatment paradigm of AML is rapidly changing. On the one hand, a plethora of new targeted drugs with good tolerability profiles are becoming available, offering the possibility to achieve a prolonged remission to many patients not otherwise eligible for more intensive therapies. On the other hand, better tools to assess patients’ fitness and improvements in the selection and management of those undergoing allo-HCT will hopefully reduce treatment-related mortality and complications. Importantly, a detailed genetic characterization of AML has become of paramount importance to choose the best therapeutic option in both intensively treated and unfit patients. Finally, improving supportive care and quality of life is of major importance in this age group, especially for the minority of patients that are still candidates for palliative care because of very poor clinical conditions or unwillingness to receive active treatments. In the present review, we discuss the evolving approaches in the treatment of older AML patients, which is becoming increasingly challenging following the advent of new effective drugs for a very heterogeneous and complex population.

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Section: Discussionmentioning

confidence: 99%

Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021

Urbino

Secreto

Olivi

et al. 2021

Cancers

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“…While the efficacy of venetoclax + azacitidine has been demonstrated in VIALE-A, to date, only one study has examined its cost-effectiveness over a lifetime horizon in the USA. Using aggregated published data from VIALE-A [ 15 ], that study predicted an incremental quality-adjusted life-year (QALY) of 0.61 for venetoclax + azacitidine versus azacitidine, and an incremental cost-effectiveness ratio (ICER) of $260,343 per QALY gained [ 16 ]. At a willingness-to-pay (WTP) threshold of $150,000 per QALY, the study concluded that venetoclax + azacitidine was not cost-effective for patients with ND-AML unfit for intensive chemotherapy in the USA.…”

Section: Introductionmentioning

confidence: 99%

Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective

et al. 2022

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Objectives Using individual patient-level data from the phase 3 VIALE-A trial, this study assessed the cost-effectiveness of venetoclax in combination with azacitidine compared with azacitidine monotherapy for patients newly diagnosed with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, from a United States (US) third-party payer perspective. Methods A partitioned survival model with a 28-day cycle and three health states (event-free survival (EFS), progressive/relapsed disease, and death) was developed to estimate costs and effectiveness of venetoclax + azacitidine versus azacitidine over a lifetime (25-year) horizon. Efficacy inputs (overall survival (OS), EFS, and complete remission (CR)/CR with incomplete marrow recovery (CRi) rate) were estimated using VIALE-A data. Best-fit parametric models per Akaike Information Criterion were used to extrapolate OS until reaching EFS and extrapolate EFS until Year 5. Within EFS, the time spent in CR/CRi was estimated by applying the CR/CRi rate to the EFS curve. Past Year 5, patients still in EFS were considered cured and to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. Costs of drug acquisition, drug administration (initial and subsequent treatments), subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with health states were obtained from the literature/public data and inflated to 2021 US dollars. Health state utilities were estimated using EuroQol-5 dimension-5 level data from VIALE-A; AE disutilities were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses, and probabilistic sensitivity analyses (PSA) were also performed. Results Over a lifetime horizon, venetoclax + azacitidine versus azacitidine led to gains of 1.89 LYs (2.99 vs. 1.10, respectively) and 1.45 QALYs (2.30 vs. 0.84, respectively). Patients receiving venetoclax + azacitidine incurred higher total lifetime costs ($250,486 vs. $110,034 (azacitidine)). The ICERs for venetoclax + azacitidine versus azacitidine were estimated at $74,141 per LY and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,718 to $138,554 per QALY gained. The results were most sensitive to varying the parameters for the venetoclax + azacitidine base-case EFS parametric function (Gompertz), followed by alternative approaches for ToT estimation, treatment costs of venetoclax + azacitidine, standard mortality rate value and ToT estimation, alternative sources to inform HRU, different cure modeling assumptions, and the parameters for the venetoclax + azacitidine base-case OS parametric function (log-normal). Results from the PSA show...

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“…A better understanding of the molecular mechanisms underlying AML led to development of drugs and new treatment strategies 21 . Standard clinical treatment of AML patients consists of high-intensity induction chemotherapy and/or haematopoietic stem cell transplantation 22 . However, many newly diagnosed AML patients do not qualify for intensive chemotherapy because of their age (> 75 years) or comorbidities 23 , 24 .…”

Section: Introductionmentioning

confidence: 99%

TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia

Dratwa

Wysoczańska

Butrym

et al. 2021

Sci Rep

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Acute myeloid leukaemia (AML) is a neoplasm of immature myeloid cells characterized by various cytogenetic alterations. The present study showed that in addition to the FLT3-ITD and NPM1 mutation status, telomere length (TL) and telomerase reverse transcriptase (TERT) gene polymorphisms may affect risk and overall survival (OS) in AML. TL was longer in healthy controls than in AML patients and positively correlated with age in the patients, but not in healthy subjects. TL was found to be independently affected by the presence of the FLT3-ITD mutation. As for the TERT gene polymorphism, AML patients with the TERT rs2853669 CC genotype were characterized by significantly shorter OS than patients carrying the T allele. Another observation in our study is the difference in TL and OS in patients belonging to various risk stratification groups related to the FLT3-ITD and NPM1 mutation status. Patients with adverse risk classification (mutation in FLT3-ITD and lack of mutation in NPM1) presented with the shortest telomeres and significantly worse OS. In conclusion, OS of AML patients appears to be affected by TERT gene variability and TL in addition to other well-established factors such as age, WBC count, or FLT3-ITD and NPM1 mutation status.

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Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia

Cited by 26 publications

References 42 publications

Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021

Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021

Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective

TERT genetic variability and telomere length as factors affecting survival and risk in acute myeloid leukaemia

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