What is the treatment for olaparib (Lynparza)-induced Acute Myeloid Leukemia (AML)?

Treatment of Olaparib-Induced Acute Myeloid Leukemia (AML)

Olaparib-induced AML should be treated according to standard AML protocols, with therapy selection based on patient-specific risk factors, including intensive chemotherapy for eligible patients and allogeneic stem cell transplantation for intermediate or high-risk disease. 1

Initial Assessment and Diagnosis

• Complete diagnostic workup is essential, including peripheral blood and bone marrow examination with morphology, cytochemistry, immunophenotyping, cytogenetic and molecular analysis 1, 2
• Risk stratification must consider both patient factors (age, performance status) and disease characteristics (leukocyte count, molecular markers) 1, 2
• Pre-treatment cardiac assessment with echocardiography is recommended for patients with cardiac risk factors 1, 2

Treatment Algorithm Based on Patient Eligibility

For Patients Eligible for Intensive Therapy:

• Standard induction therapy with 7 days of cytarabine and 3 days of an anthracycline (7+3 regimen) 1
• Response assessment should be performed after hematological recovery or between days 28-35 1
• Consolidation strategy depends on risk stratification:
  • Favorable risk: High-dose cytarabine-based chemotherapy 1
  • Intermediate/adverse risk: Consider allogeneic stem cell transplantation 1

For Patients Ineligible for Intensive Therapy:

• Hypomethylating agents (azacitidine or decitabine) are recommended 1, 3
• Low-dose cytarabine may be considered as an alternative 1
• Best supportive care for patients with poor performance status and significant comorbidities 1

Management of Refractory or Relapsed Disease

• Options include clinical trials, intensive re-induction, allogeneic stem cell transplantation, and best supportive care 1
• Intensive re-induction may be more successful with longer first remission duration 1
• Allogeneic stem cell transplantation should be considered for patients in second remission 1
• Patients failing to respond to one or two cycles of induction treatment are considered refractory and may benefit from allogeneic stem cell transplantation if they have an HLA-matched donor 1

Follow-up After Treatment

• Bone marrow morphology should be evaluated every 3 months for 24 months 1
• Differential blood counts should be monitored every 3 months for 5 years 1
• Molecular MRD assessment should be performed every 3 months from bone marrow or every 4-6 weeks from peripheral blood for 24 months in patients with a molecular marker 1

Special Considerations for Olaparib-Induced AML

• Olaparib-induced AML is a rare but serious adverse event that has been reported in clinical trials 4
• The development of AML after PARP inhibitor therapy may be related to underlying genetic predisposition or prior chemotherapy exposure 4, 5
• Treatment should be conducted in centers with multidisciplinary expertise and adequate infrastructure 1, 2
• Clinical trials should be considered whenever possible 1, 6

Pitfalls and Caveats

• Anthracycline cumulative dose should be monitored due to cardiotoxicity risk 2
• Supportive care is essential and should include prophylaxis and management of tumor lysis syndrome, infection, bleeding, and thrombosis 1, 2
• Early mortality in AML is often related to bleeding, differentiation syndrome, or infection rather than disease progression 1
• Combination of olaparib with other therapies should be approached with caution, as limited data exists on such combinations in the treatment of AML 3, 5