Long-term follow-up of VIALE-C in patients with untreated AML ineligible for intensive chemotherapy

Wei, Andrew H.; Panayiotidis, Panayiotis; Montesinos, Pau; Laribi, Kamel; Иванов, В. В.; Kim, Inho; Novák, Jan; Champion, Rebecca; Fiedler, Walter; Pagoni, Maria; Bergeron, Julie; Ting, Stephen B.; Hou, Jing-Zhou; Anagnostopoulos, Achilles; McDonald, Andrew; Murthy, Vidhya; Yamauchi, Takahiro; Wang, Jianxiang; Jiang, Qi; Sun, Yan; Chyla, Brenda; Mendes, Wellington; DiNardo, Courtney D.

doi:10.1182/blood.2022016963

Cited by 20 publications

(13 citation statements)

References 2 publications

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“…This response rate is similar to the CR/CRi rate with azacitidine and venetoclax (CR/CRi 66.4%) and higher than the CR/CRi rate with low-dose cytarabine and venetoclax (CR/CRi 48.3%). 11,22 It also compares favorably with the 10-day decitabine regimens (CR/CRi 46%). 23 The median survival was 10.7 months, and the 4-week mortality was 2.3%.…”

Section: Discussionmentioning

confidence: 96%

Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients

Im,

Quann,

Agha

et al. 2024

American J Hematol

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Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m2 continuous IV infusion for 5 days. Forty‐four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4‐ and 8‐week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first‐line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.

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Section: Discussionmentioning

confidence: 96%

Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients

Im,

Quann,

Agha

et al. 2024

American J Hematol

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show abstract

“…Long-term follow-up from this study confirms these findings and notably observed that patients who achieved CR/CRi and MRD negativity with AZA/VEN had a median OS of 34.2 months [ 49 ]. Similarly, the VIALE-C study [ 50 ] randomized patients with a median age of 76 years to LDAC/VEN or LDAC/placebo, noting an improvement in the rate of CR/CRi from 13 to 48% along with survival benefit at long-term follow-up [ 51 , 52 ]. Recently, a study by Pollyea et al found that the use of alloHSCT in patients over 60 years who received AZA/VEN improved median OS compared to those who deferred alloHSCT (not reached versus 17.2 months) [ 53 ].…”

Section: Azacitidine and Venetoclax: Moving Up The Ranksmentioning

confidence: 99%

Recent advances in targeted therapies in acute myeloid leukemia

2023

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Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.

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“…The best performing subgroup receiving LDC+ VEN were patients with an NPM1 mutation, who had a response rate of 78% and median OS exceeding 2 years. 30…”

Section: A Positive Phase 3 Outcome and The Impact On Clinical Practicementioning

confidence: 99%

“…The best performing subgroup receiving LDC+ VEN were patients with an NPM1 mutation, who had a response rate of 78% and median OS exceeding 2 years. 30 The VIALE-A study enrolled 431 patients, also in a 2:1 ratio, to either AZA or placebo in combination with VEN. With a median follow-up time of 20.5 months, the primary analysis of the VIALE-A study was positive, with median OS in the AZA plus VEN arm 14.7 months, compared to 9.6 months in the placebo arm (HR, 0.66 [95% CI, 0.52-0.85]; P < 0.001), with a substantially improved response rate (CR/CRi, 66% versus 28%).…”

Section: A Positive Phase 3 Outcome and The Impact On Clinical Practicementioning

confidence: 99%

“…A final follow‐up performed with 34.7 months of median follow‐up time demonstrated 2‐year OS to be 21.5% in the LDC+ VEN arm, compared with 12.4% for patients in the LDC + placebo arm (number needed to improve survival at 2 years of 11). The best performing subgroup receiving LDC+ VEN were patients with an NPM1 mutation, who had a response rate of 78% and median OS exceeding 2 years 30 …”

Section: A Positive Phase 3 Outcome and The Impact On Clinical Practicementioning

confidence: 99%

See 1 more Smart Citation

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

Wei¹,

Roberts²

2023

HemaSphere

Self Cite

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Altering the natural history of acute myeloid leukemia (AML) in unfit and older patients has proved a highly challenging hurdle, despite several decades of concerted clinical trial effort. The arrival of venetoclax (VEN) to the clinical stage represents the most important therapeutic advance to date for older patients with AML. In this review, we will explain how and why VEN works, summarize its remarkable pathway to regulatory approval, and highlight the key milestones that have been important for its successful development in AML. We also provide perspectives on some of the challenges associated with using VEN in the clinic, emerging knowledge regarding mechanisms of treatment failure, and current clinical research directions likely to shape how this drug and others in this new class of anticancer agents are used in the future.

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Long-term follow-up of VIALE-C in patients with untreated AML ineligible for intensive chemotherapy

Cited by 20 publications

References 2 publications

Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients

Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients

Recent advances in targeted therapies in acute myeloid leukemia

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

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