Induction Chemotherapy for AML (other than acute promyelocytic leukemia [APL])

• Offer all patients enrolment in a clinical trial
• For patients < 60 years old eligible for intensive induction:
  • Discuss treatment options with either anthracycline plus cytarabine in “7+3” regimen
  • Consider other treatment options such as high-dose cytarabine 2 g/m² plus either idarubicin or daunorubicin, daunorubicin plus cladribine plus standard dose cytarabine or another combination of anthracycline plus cytarabine such as timed sequential therapy
• For patients ≥ 60 years old:
  • If performance status (PS) 0-2 and eligible for intensive induction, consider either:
    • Standard-dose cytarabine plus anthracycline (idarubicin, daunorubicin, or mitoxantrone)
    • Low-intensity therapy with cytarabine subcutaneously, 5-azacytidine, or decitabine
  • If PS > 2 or if PS 0-3 with significant comorbidities or if patient ≥ 75 years old, consider
    • Low-dose cytarabine subcutaneously, 5-azacytidine, or decitabine
    • Best supportive care, including transfusion support and/or hydroxyurea

Other Supportive Care:

• Central access catheter required for frequent phlebotomy and chemotherapy (vesicant) administration
• Monitoring for bleeding diatheses (disseminated intravascular coagulation)
• Transfusional support per institutional standards (red cells, platelets, cryoprecipitate)
• Growth factors rarely have a role in AML therapy (except in select regimens)
• Lumbar punctures to evaluate for central nervous system involvement by leukemia
• Monitoring for infection
  • Perform exam of mouth or throat to detect infections, including thrush
  • Look at skin for signs of focal infections, and at catheter sites
  • Imaging studies
    • Regular chest x-rays or high-resolution computerized tomography (CT) scans should be considered to detect pulmonary infection, including pulmonary aspergillosis
    • X-rays or CT scans of sinuses may detect occult fungal infections

Postinduction Therapy

• Follow-up bone marrow assessment is typically performed at 7-10 days after completing induction with standard-dose cytarabine regimen or 7-14 days after completing induction with high-dose cytarabine regimen. (This may vary with treatment facility and patient condition)
• Next therapy pathways based on the above results (degree of cytoreduction or residual disease versus clearance of disease)
  • After standard-dose cytarabine regimen, consider any of high-dose cytarabine, standard-dose cytarabine plus idarubicin or daunorubicin, other treatment options for postremission therapy after induction failure, or waiting for hematologic recovery
  • After high-dose cytarabine regimen, offer patients enrolment in a clinical trial
  • Clinical trial if response inadequate and patient performance status adequate

Postremission Therapy

• Response assessment is typically performed after postinduction therapy and hematologic recovery, and is based on cytogenetics and molecular studies.
• Allogeneic stem cell transplantation in appropriate patients (conditioning and graft versus host disease prophylaxis regimen based on patient and disease characteristics as well as donor availability)
• For patients < 60 years old:
  • If complete remission is achieved, consider consolidation therapy according to risk status:
    • In patients with favorable risk, either high- or intermediate-dose cytarabine
    • In patients with intermediate risk, consider allogeneic stem cell transplantation or high-dose cytarabine
    • In patients with poor risk or treatment-related disease or those with antecedent hematologic disorders, consider allogeneic stem cell transplantation
  • If no complete remission:
    • Clinical trial versus supportive care

• For patients ≥ 60 years old:
  • If complete remission:
    • Consider any of reduced-intensity allogeneic stem cell transplantation, standard-dose cytarabine with or without either idarubicin or daunorubicin, low-intensity therapy with hypomethylating agents (azacitidine or decitabine), or observation (evaluate options in context of patient’s performance status and medical comorbidities)
    • Multiple courses of high-dose cytarabine does not appear to increase survival compared to lower doses in patients > 60 years old, and may increase toxicity.
  • If no complete remission:
    • Clinical trial versus supportive care

Therapy for Relapsed Disease

• R > 50% after primary treatment for AML
• Definitions of relapse
  • Often based on hematologic or bone marrow evaluation
  • Molecular monitoring has shown good correlation with other definitions of relapse, but is currently limited by a lack of standardization
• No standard of care for relapse of AML
  • Consider clinical trials for all patients at relapse
  • Relapse < 1 year
    • Encourage trial participation
    • Consider alternative chemotherapy (from induction), then allogeneic stem cell transplantation
    • Supportive care if performance status does not allow further therapy
  • Relapse ≥ 1 year
    • Consider trial participation
    • Consider alternative chemotherapy (from induction), then allogeneic stem cell transplantation
    • Consider repeating the initial successful induction therapy, then allogeneic stem cell transplantation
    • Supportive care  if performance status does not allow further therapy

In 2017, the following drugs were approved to treat AML:

Midostaurin (Rydapt) was approved for the treatment of adult patients with newly diagnosed FLT3 gene positive AML in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. Rydapt is manufactured by Novartis Pharmaceuticals Corp.

Idhifa (enasidenib) was approved to treat adult patients with relapsed or refractory AML who have a IDH2 gene mutation. The drug was approved for use with the RealTime IDH2 Assay, which is used to detect specific mutations in the IDH2 gene in patients with AML. Idhifa is manufactured by the Celgene Corporation. The RealTime IDH2 Assay is manufactured by Abbott Laboratories.

Vyxeos was approved to treat adults with two types of AML: newly diagnosed therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC). Vyxeos is a fixed-combination of chemotherapy drugs daunorubicin and cytarabine that is manufactured by Jazz Pharmaceuticals.

Mylotarg (gemtuzumab ozogamicin) was approved to treat adults with newly diagnosed AML whose tumors express the CD33 antigen (CD33-positive AML) and to treat patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment. Mylotarg is manufactured by Pfizer Inc.