Advances in non-intensive chemotherapy treatment options for adults diagnosed with acute myeloid leukemia

Griffiths, Elizabeth A.; Carraway, Hetty E.; Chandhok, Namrata S; Prébet, Thomas

doi:10.1016/j.leukres.2020.106339

Cited by 22 publications

(20 citation statements)

References 75 publications

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“…Since 2017, new NIC options beyond low-dose cytarabine and HMAs have been available to extend survival in patients with AML who are not candidates for IC; however, the findings of this review suggest a substantial proportion of patients who might benefit from such treatment do not receive it (Wang 2014;Shallis et al 2019;Bories et al 2018;Griffiths et al 2020;Palmieri et al 2020). Across identified studies, patients treated with NIC experienced longer OS than those who received NAAT.…”

Section: Discussionmentioning

confidence: 93%

Patterns of undertreatment among patients with acute myeloid leukemia (AML): considerations for patients eligible for non-intensive chemotherapy (NIC)

Hubscher

Sikirica

Bell

et al. 2021

J Cancer Res Clin Oncol

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Acute myeloid leukemia (AML) is a life-threatening malignancy that is more prevalent in the elderly. Because the patient population is heterogenous and advanced in age, choosing the optimal therapy can be challenging. There is strong evidence supporting antileukemic therapy, including standard intensive induction chemotherapy (IC) and non-intensive chemotherapy (NIC), for older patients with AML, and guidelines recommend treatment selection based on a patient’s individual and disease characteristics as opposed to age alone. Nonetheless, historic evidence indicates that a high proportion of patients who may be candidates for NIC receive no active antileukemic treatment (NAAT), instead receiving only best supportive care (BSC). We conducted a focused literature review to assess current real-world patterns of undertreatment in AML. From a total of 25 identified studies reporting the proportion of patients with AML receiving NAAT, the proportion of patients treated with NAAT varied widely, ranging from 10 to 61.4% in the US and 24.1 to 35% in Europe. Characteristics associated with receipt of NAAT included clinical factors such as age, poor performance status, comorbidities, and uncontrolled concomitant conditions, as well as sociodemographic factors such as female sex, unmarried status, and lower income. Survival was diminished among patients receiving NAAT, with reported median overall survival values ranging from 1.2 to 4.8 months compared to 5 to 14.4 months with NIC. These findings suggest a proportion of patients who are candidates for NIC receive NAAT, potentially forfeiting the survival benefit of active antileukemic treatment.

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Section: Discussionmentioning

confidence: 93%

Patterns of undertreatment among patients with acute myeloid leukemia (AML): considerations for patients eligible for non-intensive chemotherapy (NIC)

Hubscher

Sikirica

Bell

et al. 2021

J Cancer Res Clin Oncol

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“…20,26 When induction therapy is not possible due to the severe comorbidity and complicated hematological anamnesis of the patient, palliative therapy by low-dose cytarabine is used. 18,27 One of the main predictors of unfavorable prognosis for leukemia patients is the resistance of tumor cells to cytotoxic drugs, which can be both initially found at diagnosis and acquired as a result of chemotherapy. 28 The presence of an aberrant immunophenotype, as well as a mixed phenotype of leukemia, is an additional marker of poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“… 20 , 26 When induction therapy is not possible due to the severe comorbidity and complicated hematological anamnesis of the patient, palliative therapy by low‐dose cytarabine is used. 18 , 27 …”

Section: Discussionmentioning

confidence: 99%

Drug responsiveness of leukemic cells detected in vitro at diagnosis correlates with therapy response and survival in patients with acute myeloid leukemia

et al. 2021

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Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and chemotherapy remains the most commonly used treatment approach for this group of hematological disorders. Drug resistance is one of the predictors of unfavorable prognosis for leukemia patients. Aim:The purpose of this study was to perform a retrospective analysis of the survival rate in AML patients according to age, tumor status, and chemotherapy regimen received and to analyze the therapy response of AML patients depending on the treatment received, initial responsiveness of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis and expression of immunological markers. Methods:The survival of AML patients (n = 127) was analyzed using the Kaplan-Meier method. Drug sensitivity of tumor cells of AML patients (n = 37) and the expression of immunological markers were evaluated by the WST test and flow cytometry, respectively. Correlation analysis was performed using Spearman's rank order correlation coefficient.Results: We found the treatment regimen to be the defining factor in the patient survival rate. In addition, the initial responsiveness of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis correlated with the therapy response of AML: patients with high tumor cell sensitivity to particular cytotoxic drugs demonstrated a good response to treatment including these drugs, and patients with initial resistance of tumor cells to a particular chemotherapeutic agents and received it according to the clinical protocols demonstrated a poor response to antitumor therapy. Correlations of drug resistance in leukemic cells with the expression of immature and aberrant immunophenotype markers as established unfavorable prognostic factors confirm our assumption. Conclusion:The evaluation of the responsiveness of tumor cells to chemotherapy in vitro at diagnosis can be a useful tool for predicting the response of leukemia patients to planned chemotherapy. Maria A. Kolesnikova and Aleksandra V. Sen'kova contributed equally to this work.

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“…For decades, the mainstay of treatment has included intensive multi-phased chemotherapy regimens for medically fit patients consisting of anthracycline/cytarabine-based induction chemotherapy followed by cytarabine-based consolidation, and potentially allogeneic hematopoietic cell transplantation (allo-HCT) [ 2 ]. Lower-intensity alternatives, including various targeted agents (e.g., the BCL-2 inhibitor venetoclax, the FLT3-inhibitor gilteritinib or IDH1/2 inhibitors) and hypomethylating agents (HMA), are often used for patients with significant medical comorbidities or elderly individuals who would not tolerate intensive induction chemotherapy [ 3 , 4 ]. The prognosis of an individual AML patient is dependent on multiple variables including a patient’s age and functional status as well as the type of AML and genetic factors [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?

Allen¹,

Zeidan²,

Bewersdorf³

2021

Life

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Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific antibodies have been developed and shown early encouraging results. Bispecific antibodies comprise a wide variety of constructs that share the common concept of simultaneous binding of a surface target on malignant cells and most commonly CD3 on T cells leading to an endogenous, HLA-independent, immune response against malignant cells. However, the use of bispecific antibodies in AML has been limited by the absence of highly specific leukemia-associated antigens leading to on-target, off-leukemia side effects as well as reduced efficacy due to antigen escape. Herein, we discuss the history and evolution of bispecific T cell engagers as well as various adaptations such as dual affinity retargeting antibodies, bi- and tri-specific killer engager antibodies. Common side effects including cytokine release syndrome and management thereof are highlighted. Lastly, we expound on the future direction and integration of such antibody-based therapies with other immunotherapies (programmed cell death-1 inhibitors and chimeric antigen receptor T cells).

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Advances in non-intensive chemotherapy treatment options for adults diagnosed with acute myeloid leukemia

Cited by 22 publications

References 75 publications

Patterns of undertreatment among patients with acute myeloid leukemia (AML): considerations for patients eligible for non-intensive chemotherapy (NIC)

Patterns of undertreatment among patients with acute myeloid leukemia (AML): considerations for patients eligible for non-intensive chemotherapy (NIC)

Drug responsiveness of leukemic cells detected in vitro at diagnosis correlates with therapy response and survival in patients with acute myeloid leukemia

BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?

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