scholarly journals New Targeted Agents in Acute Myeloid Leukemia: New Hope on the Rise

2019 ◽  
Vol 20 (8) ◽  
pp. 1983 ◽  
Author(s):  
Stephan R. Bohl ◽  
Lars Bullinger ◽  
Frank G. Rücker
Keyword(s):  
Acute Myeloid Leukemia ◽  
Patient Outcomes ◽  
Myeloid Leukemia ◽  
Treatment Strategies ◽  
Gemtuzumab Ozogamicin ◽  
Molecular Heterogeneity ◽  
Targeted Agents ◽  
Fda Approval ◽  
Cytotoxic Treatment ◽  
Acute Myeloid

The therapeutic approach for acute myeloid leukemia (AML) remains challenging, since over the last four decades a stagnation in standard cytotoxic treatment has been observed. But within recent years, remarkable advances in the understanding of the molecular heterogeneity and complexity of this disease have led to the identification of novel therapeutic targets. In the last two years, seven new targeted agents (midostaurin, gilteritinib, enasidenib, ivosidenib, glasdegib, venetoclax and gemtuzumab ozogamicin) have received US Food and Drug Administration (FDA) approval for the treatment of AML. These drugs did not just prove to have a clinical benefit as single agents but have especially improved AML patient outcomes if they are combined with conventional therapy. In this review, we will focus on currently approved and promising upcoming agents and we will discuss controversial aspects and limitations of targeted treatment strategies.

scholarly journals Single-agent and combination biologics in acute myeloid leukemia

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 548-556 ◽  
Author(s):  
Guillaume Richard-Carpentier ◽  
Courtney D. DiNardo
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Gemtuzumab Ozogamicin ◽  
Targeted Agents ◽  
Newly Diagnosed ◽  
Rational Drug ◽  
Genomic Characterization ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway inhibitor, may be used in combination with LDAC for the same indication and improves survival compared with LDAC alone. In newly diagnosed, fit, older patients with therapy-related AML or AML with myelodysplasia-related changes, the liposome-encapsulated combination of daunorubicin and cytarabine (CPX-351) has shown superiority over the 7 + 3 regimen. The presence of an IDH1 or IDH2 mutation can be effectively targeted by ivosidenib or enasidenib, respectively. Gemtuzumab ozogamicin improves event-free survival in CD33+ patients with favorable or intermediate-risk cytogenetics. With new targeted agents available, comprehensive genomic characterization of AML at diagnosis and relapse is increasingly necessary to select optimal treatment. Herein, we review the new single-agent and combination biologics (omitting FLT3 inhibitors, which are discussed separately) and provide recommendations on how to best use and manage patients on these regimens in clinical practice.

scholarly journals Intermediate-risk acute myeloid leukemia therapy: current and future

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Konstanze Döhner ◽  
Peter Paschka
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Intensive Therapy ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
High Dose ◽  
Genetic Profile ◽  
Molecular Heterogeneity ◽  
Intermediate Risk ◽  
Acute Myeloid

Abstract In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.

scholarly journals The role of targeted therapy in the management of patients with AML

2017 ◽  
Vol 1 (24) ◽  
pp. 2281-2294 ◽  
Author(s):  
Alexander E. Perl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapy ◽  
Drug Therapy ◽  
Myeloid Leukemia ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
Targeted Agents ◽  
The Us ◽  
Acute Myeloid

Abstract Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration’s approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment.

scholarly journals FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia

2018 ◽  
Vol 24 (14) ◽  
pp. 3242-3246 ◽  
Author(s):  
Emily Y. Jen ◽  
Chia-Wen Ko ◽  
Jee Eun Lee ◽  
Pedro L. Del Valle ◽  
Antonina Aydanian ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Fda Approval ◽  
Acute Myeloid

scholarly journals The role of targeted therapy in the management of patients with AML

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Alexander E. Perl
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapy ◽  
Drug Therapy ◽  
Myeloid Leukemia ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
Targeted Agents ◽  
The Us ◽  
Acute Myeloid

AbstractDrug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration’s approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment.

Intermediate-risk acute myeloid leukemia therapy: current and future

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Konstanze Döhner ◽  
Peter Paschka
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Intensive Therapy ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
High Dose ◽  
Genetic Profile ◽  
Molecular Heterogeneity ◽  
Intermediate Risk ◽  
Acute Myeloid

In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.

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