Acute Myeloid Leukemia: Update on Upfront Therapy in Elderly Patients

Keiffer, Gina; Palmisiano, Neil

doi:10.1007/s11912-019-0823-1

Cited by 14 publications

(13 citation statements)

References 41 publications

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“…Most previous HLA-mismatched stem cell transplantation studies used standard-dose chemotherapy as induction therapy, followed by consolidation with high-dose cytarabine. In this study, we designed HMA plus reduced-dose IA for the AML cohort, which is based on the following considerations: Most of the elderly AML patients were secondary AML preceded by MDS or with myelodysplasia-related changes ( 43 ); poor-risk cytogenetics increased with advancing age, with 51% of patients older than 75 years reported to have poor-risk cytogenetics ( 44 ); In this study, 53% (9/17) of AML patients were in the unfavorable-risk category; According to the NCCN guidelines (version 3.2020), elderly AML patients with unfavorable-risk cytogenetics can be treated with a hypomethylating agent (HMA) or a standard dose of IA (3 + 7). We used DAC plus IA(3 + 5) followed with HLA-mismatched allo-TLI for AML cohort.…”

Section: Discussionmentioning

confidence: 99%

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

Huang

Hong

Zhou³

et al. 2021

Front. Oncol.

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ObjectiveTo evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS).MethodsWe carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3+ allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor.ResultsA total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61–97%) and 60% (13–88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1.ConclusionElderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients.Clinical Trial Registrationhttps://www.chictr.org.cn/showproj.aspx?proj=20112.

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Section: Discussionmentioning

confidence: 99%

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

Huang

Hong

Zhou³

et al. 2021

Front. Oncol.

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“…4 The BM blast percentage went from 89% to 7% microscopically and from 65% to 2% by FCM after one cycle of OXA. 5 The BM percentage went from 15% to 0% microscopically and from 9% to 1-2% by FCM with disappearance (0 of 300 nuclei) of the FISH-detected split signal (10%/30 of 300 nuclei) pre-therapy) due to inv(16)/CBFB rearrangement after one cycle of OXA.…”

Section: Efficacymentioning

confidence: 97%

“…gov). Despite recent advances in therapy, the five-year overall survival remains < 30% and prognosis is grim in patients who experience a recurrence of their disease after first-line induction therapy, with <10% surviving five years after relapse [1][2][3][4][5][6][7][8]. There is an urgent need for effective new treatment strategies for relapsed AML [9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

A Phase 1B Clinical Study of Combretastatin A1 Diphosphate (OXi4503) and Cytarabine (ARA-C) in Combination (OXA) for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Uckun

Cogle

Lin

et al. 2019

Cancers

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Combretastatin A1 (OXi4503) is a dual-function drug with vascular disrupting and cytotoxic properties that has exhibited single-agent anti-leukemia activity in murine xenograft models of acute myeloid leukemia (AML) and in a prior Phase 1A clinical study for relapsed/refractory (R/R) AML. The purpose of the present multicenter Phase 1B study was to define the maximum tolerated dose (MTD) and safety profile of OXi4503 and cytarabine (ARA-C) administered in combination (OXA). At four centers, 29 patients with R/R AML or myelodysplastic syndrome (MDS) were treated with OXA. The most common grade 3/4 treatment-emergent adverse events (AEs) were febrile neutropenia (28%), hypertension (17%), thrombocytopenia (17%), and anemia (14%). There were no treatment-emergent grade 5 AEs. Drug-related serious adverse events (SAEs) developed in 4/29 patients (14%) and included febrile neutropenia (N = 2), pneumonia/acute respiratory failure (N = 1), and hypotension (N = 1). 9.76 mg/m2 was defined as the MTD of OXi4503 when administered in combination with 1 g/m2 ARA-C. In 26 evaluable AML patients, there were 2 complete remissions (CR), 2 complete remissions with incomplete count recovery (CRi) and one partial response (PR), for an overall response rate (ORR) of 19%. The median overall survival (OS) time for the four patients who achieved a CR/CRi was 528 days (95% CI: 434–NA), which was significantly longer than the median OS time of 113 days (95% CI: 77–172) for the remaining 22 patients who did not achieve a CR/CRi (Log Rank Chi Square = 11.8, p-value = 0.0006). The safety and early evidence of efficacy of the OXA regimen in R/R AML patients warrant further investigation in a Phase 2 clinical study.

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“… 31 Unlike the precise current stratification of young and middle-aged AML patients, the clinical treatment of elderly patients is still ineffective, and their prognosis is adverse. 32 In this paper, we did correlation studies with genetic mutations, clinical features, and prognosis comprehensively evaluated the clinical and biological characteristics of elderly AML patients, and provided some reference to this particular group’s prognosis and clinical treatment.…”

Section: Introductionmentioning

confidence: 99%

Correlation Analysis and Prognostic Impacts of Biological Characteristics in Elderly Patients with Acute Myeloid Leukemia

Li¹,

Li²,

Wang³

et al. 2022

CIA

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Background The significant heterogeneity of elderly AML patients’ biological features has caused stratification difficulties and adverse prognosis. This paper did a correlation study between their genetic mutations, clinical features, and prognosis to further stratify them. Methods 90 newly diagnosed elderly acute myeloid leukemia (AML) patients (aged ≥60 years) who detected genetic mutations by next-generation sequencing (NGS) were enrolled between April 2015 and March 2021 in our medical center. Results A total of 29 genetic mutations were identified in 82 patients among 90 cases with a frequency of 91.1%. DNMT3A, BCOR, U2AF1, and BCORL1 mutations were unevenly distributed among different FAB classifications ( p < 0.05). DNMT3A, IDH2, NPM1, FLT3-ITD, ASXL1, IDH1, SRSF2, BCOR, NRAS, RUNX1, U2AF1, MPO, and WT1 mutations were distributed differently when an immunophenotype was expressed or not expressed ( p <0.05). NPM1 and FLT3-ITD had higher mutation frequencies in patients with normal chromosome karyotypes than abnormal chromosome karyotypes ( p <0.001, p =0.005). DNMT3A and NRAS mutations predicted lower CR rates. DNMT3A, TP53, and U2AF1 mutations were related to unfavorable OS. TET2 mutation with CD123+, CD11b+ or CD34- predicted lower CR rate. IDH2+/CD34- predicted lower CR rate. ASXL1+/CD38+ and SRSF2+/CD123- predicted shorter OS. Conclusion The study showed specific correlations between elderly AML patients’ genetic mutations and clinical features, some of which may impact prognosis.

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Acute Myeloid Leukemia: Update on Upfront Therapy in Elderly Patients

Cited by 14 publications

References 41 publications

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3+ T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients

A Phase 1B Clinical Study of Combretastatin A1 Diphosphate (OXi4503) and Cytarabine (ARA-C) in Combination (OXA) for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Correlation Analysis and Prognostic Impacts of Biological Characteristics in Elderly Patients with Acute Myeloid Leukemia

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