What blood tests should be ordered to assess AML status before stopping Venclexta (venetoclax)?

Blood Testing Before Stopping Venetoclax in AML

Before discontinuing venetoclax therapy in AML, order a bone marrow aspirate with blast count assessment, multiparameter flow cytometry for measurable residual disease (MRD), and molecular testing for mutations (particularly NPM1, IDH1/2, FLT3, and TP53) to determine disease status. 1

Essential Testing Components

Bone Marrow Assessment

• Bone marrow aspirate is mandatory to evaluate blast percentage and determine if morphologic remission (<5% blasts) has been achieved 1
• Count at least 500 nucleated cells on marrow smears containing spicules for accurate blast enumeration 1
• Include myeloblasts, monoblasts, and promonocytes in the blast count 1
• If aspirate is inadequate (dry tap), perform a bone marrow trephine biopsy with immunohistochemistry for CD34 to assess blast burden 1

Flow Cytometry for MRD

• Multiparameter flow cytometry (minimum 3-4 colors) should be performed to detect MRD using the aberrant immunophenotype established at diagnosis 1
• Flow cytometric MRD assessment from bone marrow is recommended after treatment cycles and can detect residual disease below morphologic thresholds 1
• The absence of MRD (particularly in patients achieving complete remission) correlates with better outcomes 1

Molecular Testing

• Molecular MRD assessment should be performed if a molecular marker (NPM1, IDH1/2, RUNX1-RUNX1T1, or other fusion transcripts) was present at diagnosis 1
• Molecular testing can be performed from both peripheral blood and bone marrow 1
• Repeat mutation analysis for key genes including NPM1, FLT3, IDH1/2, TP53, KRAS/NRAS, and SF3B1, as acquisition of new mutations or changes in mutational burden can indicate emerging resistance 2

Timing of Assessment

• Perform bone marrow biopsy on days 21-28 of each venetoclax cycle for response assessment, potentially earlier (day 21) for patients receiving venetoclax with decitabine 1
• If morphologic remission is achieved and counts recover, subsequent bone marrow biopsies can be repeated at 3-6 month intervals rather than after every cycle 1
• If blood counts worsen over time despite prior remission, repeat bone marrow biopsy immediately to rule out relapsed disease before stopping therapy 1

Additional Laboratory Monitoring

• Complete blood count with differential to assess peripheral blast count and cytopenias 1
• Comprehensive metabolic panel to evaluate organ function 1
• Cytogenetic analysis if new chromosomal abnormalities are suspected, as relapse may be driven by increased cytogenetic complexity 2

Critical Pitfalls to Avoid

• Do not rely solely on peripheral blood counts to determine disease status, as bone marrow assessment is essential even when peripheral counts appear normal 1
• Do not use flow cytometric CD34 counts as a substitute for visual blast assessment, as not all blasts express CD34 and processing artifacts can cause errors 1
• Do not stop venetoclax based on cytopenias alone without confirming disease status, as prolonged cytopenias can occur even in morphologic remission with venetoclax-based therapy 1
• If considering stopping therapy due to worsening counts, always rule out relapsed disease with bone marrow biopsy before attributing cytopenias to drug toxicity 1

Predictors of Response and Resistance

• NPM1 mutations predict better responses to venetoclax therapy and should be monitored 3, 2
• TP53, KRAS/NRAS, FLT3-ITD, and SF3B1 mutations are associated with worse outcomes and venetoclax resistance 3, 2
• Adverse cytogenetics predict inferior survival with venetoclax-based therapy 2
• Monocytic phenotype AML shows decreased sensitivity to venetoclax 3