The new perspectives of targeted therapy
in acute myeloid leukemia

Walasek, Angela

doi:10.17219/acem/81610

Cited by 19 publications

(14 citation statements)

References 54 publications

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“…The goal of these conjugated monoclonal antibodies is to restrict the delivery of the drug to the antibody-binding cells in order to increase its concentration in malignant cells and decrease its toxicity to healthy cells. Two conjugated monoclonal antibodies have been clinically successful against childhood cancer: antiCD33 coupled with ozogamycin to treat CD33 positive acute myeloid leukaemia [ 62 ] and antiCD30 coupled with auristatin E to treat anaplastic large-cell lymphoma and Hodgkin’s lymphoma [ 36 , 42 ].…”

Section: Possibilities Of Immunotherapy For Children With Primary mentioning

confidence: 99%

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

2020

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Many primary immunodeficiencies (PIDs) are recognised as being associated with malignancies, particularly lymphoid malignancies, which represent the highest proportion of cancers occurring in conjunction with this underlying condition. When patients present with genetic errors of immunity, clinicians must often reflect on whether to manage antitumoral treatment conventionally or to take a more personalised approach, considering possible existing comorbidities and the underlying status of immunodeficiency. Recent advances in antitumoral immunotherapies, such as monoclonal antibodies, antigen-specific adoptive cell therapies or compounds with targeted effects, potentially offer significant opportunities for optimising treatment for those patients, especially with lymphoid malignancies. In cases involving PIDs, variable oncogenic mechanisms exist, and opportunities for antitumoral immunotherapies can be considered accordingly. In cases involving a DNA repair defect or genetic instability, monoclonal antibodies can be proposed instead of chemotherapy to avoid severe toxicity. Malignancies secondary to uncontrolled virus-driven proliferation or the loss of antitumoral immunosurveillance may benefit from antivirus cell therapies or allogeneic stem cell transplantation in order to restore the immune antitumoral caretaker function. A subset of PIDs is caused by gene defects affecting targetable signalling pathways directly involved in the oncogenic process, such as the constitutive activation of phosphoinositol 3-kinase/protein kinase B (PI3K/AKT) in activated phosphoinositide 3-kinase delta syndrome (APDS), which can be settled with PI3K/AKT inhibitors. Therefore, immunotherapy provides clinicians with interesting antitumoral therapeutic weapons to treat malignancies when there is an underlying PID.

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Section: Possibilities Of Immunotherapy For Children With Primary mentioning

confidence: 99%

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

2020

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“…New drug treatment options targeting FLT3 or IDH1/2 result in increasing MRD negativity in a subgroup of patients; however, a large proportion of patients do not benefit from this treatment. 68 Other options might be the use of hypomethylating agents and BCL-2 inhibitors in R/R and MRD positive patients, although with the cost of significant side effects and unclear long-term therapeutic benefit. 69 Using NK cell treatment as bridge to transplantation seems a very attractive option with minimal side effects and high CR rates.…”

Section: Revival Of the Haploidentical Transplantation: The T Cell mentioning

confidence: 99%

NK cell alloreactivity in acute myeloid leukemia in the post‐transplant cyclophosphamide era

Elssen

Ciurea

2020

American J Hematol

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Allogeneic hematopoietic stem cell transplantation (alloSCT) for myeloid leukemia remains one of the most effective anti-tumor treatments available, capable of curing an increasingly higher proportion of patients. Alloreactivity generated by T cells has limited efficacy in the early post-transplant period while most patients will relapse within 6 months after transplantation. Prior studies in T cell depleted grafts showed that, with the elimination of T cells, natural killer (NK) cells provide most of the antitumor effect in the early post-transplant period. Administration of unmodified T cells to mitigate infections and relapse will expose the patient to a high risk of graft-vshost disease (GvHD). Post-transplant cyclophosphamide (PTCy), initially used for haploidentical (haplo) donor transplants, is now also increasingly utilized in HLA matched donor transplants to prevent GvHD. In most patients, PTCy eliminates, at least in part, alloreactive T and NK cells early post-transplant. Administration of modified NK cells in the early post-transplant period makes intuitive sense to enhance the anti-tumor effect of the graft and thereby prevent relapse. Effective application of cellular therapy early after transplant has opened a new direction and could revolutionize the field of hematopoietic stem cell transplantation.

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“…Indeed, at present, all the information regarding the molecular landscape of AML marginally resulted in novel therapeutic strategies, and in the last decades, with a few exceptions, there was a general stagnation in standard chemotherapeutic approaches. Fortunately, this scenario is gradually changing (8). In this review, we provided an overview of several therapeutic approaches to target specific genetic lesion of pediatric AML, with special attention on drugs that recently received US Food and Drug Administration (FDA) approval for AML treatment together with promising strategies to treat definite subgroup of pediatric AML.…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapies for Pediatric AML: Gaps and Perspective

2019

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Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by numerous cytogenetic and molecular aberrations that accounts for ~25% of childhood leukemia diagnoses. The outcome of children with AML has increased remarkably over the past 30 years, with current survival rates up to 70%, mainly due to intensification of standard chemotherapy and improvements in risk classification, supportive care, and minimal residual disease monitoring. However, childhood AML prognosis remains unfavorable and relapse rates are still around 30%. Therefore, novel therapeutic approaches are needed to increase the cure rate. In AML, the presence of gene mutations and rearrangements prompted the identification of effective targeted molecular strategies, including kinase inhibitors, cell pathway inhibitors, and epigenetic modulators. This review will discuss several new drugs that recently received US Food and Drug Administration approval for AML treatment and promising strategies to treat childhood AML, including FLT3 inhibitors, epigenetic modulators, and Hedgehog pathway inhibitors.

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The new perspectives of targeted therapy in acute myeloid leukemia

Cited by 19 publications

References 54 publications

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

The Possibilities of Immunotherapy for Children with Primary Immunodeficiencies Associated with Cancers

NK cell alloreactivity in acute myeloid leukemia in the post‐transplant cyclophosphamide era

Targeted Therapies for Pediatric AML: Gaps and Perspective

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