Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Relapsed or primary refractory AML: moving past MEC and FLAG-ida.

ABSTRACT:

Purpose of review

Treatment of relapsed and refractory acute myeloid leukemia (AML) is still very challenging, with poor response rates and low chance for cure. This is especially true when treating patients who are elderly, have multiple comorbidities, or who are too unfit for traditional salvage chemotherapy regimens.

Recent findings

Recently, advances in the treatment of relapsed/refractory AML utilizing novel chemotherapy combinations, hypomethylating, and targeted therapies have shown promising results.

Summary

Several early-phase studies with novel targeted therapy combinations have demonstrated encouraging results warranting larger, comparative studies. This has expanded the access of treatment for patients with relapsed/refractory AML who cannot receive traditional salvage chemotherapy. These newer treatments have the potential to outperform traditional chemotherapy as well.

SUBMITTER: Koenig K

PROVIDER: S-EPMC7015186 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Relapsed or primary refractory AML: moving past MEC and FLAG-ida.

Koenig Kristin K Mims Alice A

Current opinion in hematology 20200301 2

<h4>Purpose of review</h4>Treatment of relapsed and refractory acute myeloid leukemia (AML) is still very challenging, with poor response rates and low chance for cure. This is especially true when treating patients who are elderly, have multiple comorbidities, or who are too unfit for traditional salvage chemotherapy regimens.<h4>Recent findings</h4>Recently, advances in the treatment of relapsed/refractory AML utilizing novel chemotherapy combinations, hypomethylating, and targeted therapies h ...[more]

PMID: 31904664

Similar Datasets

Venetoclax Combined With FLAG-IDA in Refractory or Relapsed Acute Myeloid Leukemia.

Project description:IntroductionThe prognosis of patients with refractory or relapsed AML (R/R-AML) is very limited. To (re)achieve complete remission, there has recently been increasing evidence that the combination of venetoclax (VEN) with chemotherapy is associated with improved outcomes.Patients and methodsOur retrospective, single-center study of 53 R/R-AML patients with a median follow-up time of 11.0 months compared standard salvage chemotherapy (FLAG-Ida or HAM in n = 35 patients) with a combination of venetoclax (VEN) and FLAG-Ida (FLAVIDA in n = 18 patients) concerning safety and efficacy.ResultsRegarding the primary endpoints, there was a statistically significant increased event free survival (EFS) in the FLAVIDA group compared to patients with standard chemotherapy based on the univariate log-rank-test and in the multivariate Cox regression analysis (HR 0.22 [95% CI 0.05, 0.97]). There were no differences between the two groups in terms of patients developing febrile neutropenia CTCAE III° and IV° or a delay in hematological recovery. In addition, a clear trend towards an improved overall response rate (78% vs. 51%) was demonstrated in the FLAVIDA group.ConclusionsThe FLAVIDA regimen represents a promising treatment alternative for R/R AML patients with a high response rate and significantly improved EFS compared to standard chemotherapy.

| S-EPMC11613577 | biostudies-literature

Midostaurin, bortezomib and MEC in relapsed/refractory acute myeloid leukemia.

Project description:Targeting aberrant tyrosine kinase activity may impact clinical outcome in acute myeloid leukemia (AML). We conducted a phase I study of the tyrosine kinase inhibitor midostaurin with bortezomib alone and in combination with chemotherapy in patients with AML. Patients on dose levels 1 and 2 (DL1 & 2) received midostaurin 50 mg bid and escalating doses of bortezomib (1 to 1.3 mg/m2). Patients on DL3 or higher received midostaurin and bortezomib following chemotherapy with mitoxantrone, etoposide, cytarabine (MEC). None of the patients enrolled to DL1 & 2 had dose-limiting toxicities (DLTs) or a clinical response. Among patients enrolled to DL3 or higher, DLTs were peripheral neuropathy, decrease in ejection fraction and diarrhea. A 56.5% CR rate and 82.5% overall response rate (CR + CR with incomplete neutrophil or platelet count recovery) were observed. The midostaurin/bortezomib/MEC combination is active in refractory/relapsed AML, but is associated with expected drug-related toxicities (NCT01174888).

| S-EPMC5360182 | biostudies-literature

DNA methylation of Relapsed/Refractory AML

Project description:Genome wide DNA methylation profiling of blood and bone marrow of Pediatric Patients with Relapsed/Refractory Acute Myeloid Leukemia. The Illumina Infinium EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across over 860,000 CpGs.

2023-12-31 | GSE225239 | GEO

Haploidentical transplantation in primary refractory/relapsed secondary vs de novo AML: from the ALWP/EBMT.

Project description:AbstractWe compared the outcomes of haploidentical stem cell transplantation (haplo-HSCT) with posttransplant cyclophosphamide (PTCy) in 719 patients with primary refractory (PR) or first relapse (Rel) secondary acute myeloid leukemia (sAML; n = 129) vs those with de novo AML (n = 590), who received HSCT between 2010 and 2022. A higher percentage of patients with sAML vs de novo AML had PR disease (73.6% vs 58.6%; P = .002). In 81.4% of patients with sAML , the antecedent hematological disorder was myelodysplastic syndrome. Engraftment was 83.5% vs 88.4% in sAML and de novo AML, respectively (P = .13). In multivariate analysis, haplo-HSCT outcomes did not differ significantly between the groups: nonrelapse mortality hazard ratio (HR), 1.38 (95% confidence interval [CI], 0.96-1.98; P = .083), relapse incidence HR, 0.68 (95% CI, 0.4.7.-1.00; P = .051). The HRs for leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, and GVHD and relapse-free survival were 0.99 (95% CI, 0.76-1.28; P = .94), 0.99 (95% CI, 0.77-1.29; P = .97), and 0.99 (95% CI, 0.77-1.27; P = .94), respectively. We conclude that outcomes of haplo-HSCT with PTCy are not different for PR/Rel sAML in comparison with PR/Rel de novo AML, a finding of major clinical importance.

| S-EPMC11372397 | biostudies-literature

Dose-Reduced FLA-IDA in Combination with Venetoclax Is an Effective and Safe Salvage Therapy in Relapsed and Refractory Acute Myeloid Leukemia (R/R AML).

Project description:BackgroundDespite the development of targeted therapies in first-line AML, complete remissions (CR) cannot be achieved in 30-40%, and relapse rates remain high. In R/R AML the intensive treatment regimen of fludarabine, cytarabine, idarubicin combined with venetoclax (FLA-VIDA) showed improved remission rates compared to FLA-IDA. In this retrospective single-center analysis, we investigated the efficacy and safety of dose-reduced FLA-IDA with and without venetoclax to minimize the risk of infectious complications and excessive myelosuppression; Methods: Between 2011 and 2023, 89 R/R AML patients were treated with dose-reduced FLA-IDA (fludarabine 30 mg/m2 day 1-4, cytarabine 2000 mg/m2 day 1-4, idarubicin 10 mg/m2 day 1 + 4). From 2019 onwards, venetoclax was added (day 1 100 mg, day 2 200 mg, day 3-14 400 mg); Results: Significantly improved response rates were observed with 60.0% vs. 38.8% CR/CRi (p = 0.0297) and 74.5% vs. 47.3% (p = 0.032) CR/CRi/MLFS for FLA-VIDA vs. FLA-IDA. Further, with FLA-VIDA significantly improved event-free survival (EFS) was observed (p = 0.026). Overall survival (OS) was similar in FLA-VIDA and FLA-IDA treated patients. The most common treatment-related toxicities were hematological adverse events, but they were comparable between groups. The time to neutrophil and platelet recovery were similar in responding patients treated with FLA-VIDA vs. FLA-IDA; Conclusions: Dose-reduced FLA-VIDA significantly improved response rates without increases in toxicity, showing promise for an improved R/R AML treatment.

| S-EPMC11592574 | biostudies-literature

Decitabine and vorinostat with FLAG chemotherapy in pediatric relapsed/refractory AML: Report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium.

Project description:Survival outcomes for relapsed/refractory pediatric acute myeloid leukemia (R/R AML) remain dismal. Epigenetic changes can result in gene expression alterations which are thought to contribute to both leukemogenesis and chemotherapy resistance. We report results from a phase I trial with a dose expansion cohort investigating decitabine and vorinostat in combination with fludarabine, cytarabine, and G-CSF (FLAG) in pediatric patients with R/R AML [NCT02412475]. Thirty-seven patients enrolled with a median age at enrollment of 8.4 (range, 1-20) years. There were no dose limiting toxicities among the enrolled patients, including two patients with Down syndrome. The recommended phase 2 dose of decitabine in combination with vorinostat and FLAG was 10 mg/m2 . The expanded cohort design allowed for an efficacy evaluation and the overall response rate among 35 evaluable patients was 54% (16 complete response (CR) and 3 complete response with incomplete hematologic recovery (CRi)). Ninety percent of responders achieved minimal residual disease (MRD) negativity (<0.1%) by centralized flow cytometry and 84% (n = 16) successfully proceeded to hematopoietic stem cell transplant. Two-year overall survival was 75.6% [95%CI: 47.3%, 90.1%] for MRD-negative patients vs. 17.9% [95%CI: 4.4%, 38.8%] for those with residual disease (p < .001). Twelve subjects (34%) had known epigenetic alterations with 8 (67%) achieving a CR, 7 (88%) of whom were MRD negative. Correlative pharmacodynamics demonstrated the biologic activity of decitabine and vorinostat and identified specific gene enrichment signatures in nonresponding patients. Overall, this therapy was well-tolerated, biologically active, and effective in pediatric patients with R/R AML, particularly those with epigenetic alterations.

| S-EPMC8986610 | biostudies-literature

A randomized comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS: the UK NCRI AML19 trial.

Project description:Liposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients with secondary acute myeloid leukemia (AML); to date, there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). A total of 189 patients were randomized (median age, 56 years). Per clinical criteria, 49% of patients had de novo AML, 20% had secondary AML, and 30% had high-risk MDS. MDS-related cytogenetics were present in 73% of the patients, with a complex karyotype in 49%. TP53 was the most common mutated gene, in 43%. Myelodysplasia-related gene mutations were present in 75 (44%) patients. The overall response rate (CR + CRi) after course 2 was 64% and 76% for CPX-351 and FLAG-Ida, respectively. There was no difference in OS (13.3 months vs 11.4 months) or event-free survival in multivariable analysis. However, relapse-free survival was significantly longer with CPX-351 (median 22.1 vs 8.35 months). There was no difference between the treatment arms in patients with clinically defined secondary AML or those with MDS-related cytogenetic abnormalities; however, an exploratory subgroup of patients with MDS-related gene mutations had significantly longer OS with CPX-351 (median 38.4 vs 16.3 months). In conclusion, the OS of younger patients with adverse risk AML/MDS was not significantly different between CPX-351 and FLAG-Ida.

| S-EPMC10425682 | biostudies-literature

DNA methylation of Relapsed/Refractory AML

Project description:DNA methylation of Relapsed/Refractory AML

| PRJNA934390 | ENA

Outcome of patients with relapsed or refractory acute myeloid leukemia treated with Mito-FLAG salvage chemotherapy.

Project description:PurposeCurative intended treatment is challenging in patients with relapsed or refractory acute myeloid leukemia (r/r AML) and associated with a dismal prognosis for long-term survival. Despite novel treatment options, the majority of patients are treated with chemotherapy-based regimens. Although widely used, little data exist on the combination of fludarabine, cytarabine, granulocyte colony stimulating factor (FLAG) and mitoxantrone as salvage strategy for r/r AML.Materials and methodsSixty-six patients receiving Mito-FLAG for r/r AML treated at a German tertiary care center between 2009 and 2019 were analyzed with regard to response rates, survival and safety profile.ResultsOverall response rate was 75.8% with 56.1% of patients achieving complete remission (CR) and 19.7% partial remission (PR). After a median follow-up of 54 months, median overall survival (OS) was 13 months. Patients transitioned to allogeneic hematopoietic stem cell transplantation (alloHSCT) (75.8%) showed a significant improvement in OS with a median OS of 17 (95% CI 8.5-25.4) months vs 3 (95% CI 1.7-4.3) months (p < 0.001). 30- and 60-day mortality rates for all patients after the initial cycle of Mito-FLAG were 4.5% and 7.6%, respectively.ConclusionThe Mito-FLAG salvage protocol represents an effective and feasible treatment regimen for r/r AML. Importantly, a high rate of transition to successful alloHSCT with the aim of long-term disease-free survival has been shown.

| S-EPMC9349069 | biostudies-literature

Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML.

Project description:Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.

| S-EPMC10027507 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data