Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States

Zeidan, Amer M.; Wang, Rong; Wang, Xiaoyi; Shallis, Rory M.; Podoltsev, Nikolai A.; Bewersdorf, Jan Philipp; Huntington, Scott F.; Neparidze, Natalia; Giri, Smith; Gore, Steven D.; Davidoff, Amy J.; Ma, Xiaomei

doi:10.1182/bloodadvances.2020001779

Cited by 77 publications

(62 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As expected ELN risk group and attainment of CR were key determinants of survival outcomes in our cohort 27 . In comparison, a recent survival analysis from a large population based data‐set including over 2000 AML patients treated with HMA monotherapy demonstrated a median survival of 7 to 8 months 21 . Furthermore, results from the recently completed randomized placebo control trial (VIALE‐A) comparing venetoclax and azacitidine with placebo and azacitidine demonstrated superior complete response rates of 66.4%, with the former regimen vs 28.3% translating to an overall survival benefit with the addition of venetoclax (median survival of 14.7 vs 9.6 months respectively; P < .001) 28 …”

Section: Discussionsupporting

confidence: 60%

“…Prior to its approval in combination with HMA or low dose cytarabine, therapy was limited to HMA with modest responses, longer time to response and marginal survival benefit. 21 Our observations are reflective of both published clinical trial and "real world" reports with a comprehensive comparison provided in Table S3. 10,24 Low early mortality and infection rates including invasive fungal infections were similar to published clinical trial data.…”

Section: Discussionmentioning

confidence: 56%

“…The advent of venetoclax based regimens marks a paradigm shift in our treatment approach of elderly, unfit AML patients. Prior to its approval in combination with HMA or low dose cytarabine, therapy was limited to HMA with modest responses, longer time to response and marginal survival benefit 21 . Foremost, we demonstrate a CR/CRi rate of 50% in 44 newly diagnosed treatment naïve AML patients despite an enrichment of secondary and therapy related disease with adverse cytogenetics comprising two‐thirds of our cohort.…”

Section: Discussionmentioning

confidence: 71%

See 2 more Smart Citations

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients

et al. 2020

View full text Add to dashboard Cite

Venetoclax and hypomethylating agent (HMA) combination therapy is FDA-approved for elderly or unfit acute myeloid leukemia (AML) patients unable to withstand intensive chemotherapy. The primary objective of the current study was to impart our institutional experience with the above regimen, outlining response, survival outcomes, and its determinants amongst 86 treatment-naïve and relapsed/refractory AML patients. A total of 44 treatment-naïve AML patients, median age 73.5 years, enriched with secondary, therapy related and ELN adverse risk disease (n = 27) were studied. The CR/CRi rates of 50% (22 of 44 patients) were superior to 23% in a matched AML cohort treated with HMA alone (P = .005). Response rates were similar with TP53, FLT3, NPM1 and IDH mutations (P = .31). Moreover, CEPBA mutations (P = .03) and neutropenia (P = .05) emerged as predictors of complete response. Survivalwas prolonged in patients achieving CR/CRi (17 vs 3 months without CR/CRi, P < .001; conversely adverse ELN risk portended inferior survival. Amongst 42 relapsed/refractory AML patients, half received ≥2 prior therapies excluding transplant, and 15 (35.7%) had received HMA. A group of 14 patients (33.3%) attained CR/CRi; age > 65 years, AML with myelodysplasia, JAK2, DNMT3A, and BCOR mutations predicted complete response. Survival distinctions were based on CR/CRi (median survival 15 vs 3 months with/without CR/CRi; P < .001), and TP53 mutation status (P = .04). In summary, we corroborate existing reports demonstrating superior response and prolonged survival with venetoclax and HMA in treatment-naïve and relapsed/refractory AML patients regardless of genotype. Additionally, we identify unique predictors of response to therapy which require validation. 1 | INTRODUCTION Venetoclax in combination with either a hypomethylating agent (HMA) or low dose cytarabine (LDAC) gained FDA approval in November 2018 for newly diagnosed AML patients that are elderly >75 years or unfit for intensive induction regimens. 1,2 The above regimen is being increasingly utilized over the last 2 years, since the vast majority of AML patients are elderly with median age at diagnosis of 68 years. 3-7 Mechanistically venetoclax functions as a selective inhibitor of B-cell leukemia/lymphoma-2 (BCL-2), an anti-apoptotic protein which is overexpressed in leukemia stem cells (LSCs). 8 Functional studies have demonstrated that venetoclax in concert with azacitidine impacts the tricarboxylic acid cycle (TCA) cycle with reduction in α-ketoglutarate and increased succinate levels resulting in inhibition

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 71%

See 1 more Smart Citation

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Hypomethylating agents (HMAs) such as decitabine and azacitidine are DNA methyltransferase (DNMT) inhibitors which alter DNA methylation patterns, leading to increased expression of tumor suppressors and apoptosis [ 63 ]. In adults, these therapies prolong survival but rarely lead to sustained remission when used as a single agent [ 64 ]. Decitabine has also been used as maintenance therapy for adults with AML but did not protect against relapse when used in this setting [ 65 ].…”

Section: New Therapymentioning

confidence: 99%

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy

Conneely

Stevens

2021

Curr Oncol Rep

View full text Add to dashboard Cite

Purpose of Review Acute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes. Recent Findings Recent studies have revealed an increasing number of mutations, including WT1, CBFA2T3-GLIS2, and KAT6A fusions, DEK-NUP214 and NUP98 fusions, and specific KMT2A rearrangements, which are associated with poor outcomes. However, outcomes are starting to improve with the addition of therapies such as gemtuzumab ozogamicin and FLT3 inhibitors, initially developed in adult AML. Summary The combination of advanced risk stratification and ongoing improvements and innovations in treatment strategy will undoubtedly lead to better outcomes for children with AML.

show abstract

“…The treatments administered to DLBCL patients were retrieved from the NHIRD with anatomical therapeutic chemical (ATC) codes (https://www.whocc.no/atc_ddd_inde x/). 21 A change in chemotherapy was defined as any adjustment of chemotherapy except for regimen switching between CHOP and CVP or between R-CHOP and R-CVP. Rituximab was administered as a frontline treatment if the interval between the start date of rituximab and that of other chemotherapy agents was less than 42 days.…”

Section: Definition Of Chemotherapies Hbv Infections and Antiviral mentioning

confidence: 99%

Antiviral prophylaxis for hepatitis B carriers improves the prognosis of diffuse large B‐cell lymphoma in Taiwan – a population‐based study

et al. 2020

View full text Add to dashboard Cite

The prevention of hepatitis B virus (HBV) reactivation during rituximab treatment for diffuse large B-cell lymphoma (DLBCL) is important in the HBV-endemic area. This population-based study examines the impact of antiviral prophylaxis for DLBCL patients with HBV infections. We identified 3702 adult patients with newly diagnosed DLBCL between 2011 and 2015 receiving R-CHOP, R-CVP, CHOP or CVP from the Taiwan Cancer Registry. We further stratified them into three groups: HBsAg-negative patients (HBV-negative, N = 2921), HBV carriers who received antiviral prophylaxis (HBV + Px, N = 711), and HBV carriers who did not receive antiviral prophylaxis (HBV + No Px, N = 70). HBV + Px patients were the youngest, and 69Á4% received entecavir for antiviral prophylaxis. The median overall survival (mOS) of HBV-negative and HBV + Px patients was similar (74Á23 months and not reached, respectively). However, the mOS of HBV + No Px patients was only 35Á61 months (P = 0Á0028 compared with HBV + Px patients), indicating that antiviral prophylaxis improves OS in HBsAg-positive DLBCL patients. The multivariate analysis showed that the HBV status and antiviral prophylaxis was an independent prognostic factor. In conclusion, our population-based study illustrates the importance of antiviral prophylaxis in HBsAg-positive DLBCL patients. Under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients.

show abstract

Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States

Cited by 77 publications

References 38 publications

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients

Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy

Antiviral prophylaxis for hepatitis B carriers improves the prognosis of diffuse large B‐cell lymphoma in Taiwan – a population‐based study

Contact Info

Product

Resources

About