Blood Testing Before Stopping Venetoclax in AML

Essential Testing Components

The European Society for Medical Oncology recommends a bone marrow aspirate with blast count assessment, multiparameter flow cytometry for measurable residual disease (MRD), and molecular testing for mutations to determine disease status before discontinuing venetoclax therapy in AML patients 1, 2
Bone marrow aspirate is mandatory to evaluate blast percentage and determine if morphologic remission has been achieved, according to the European Society for Medical Oncology 1, 3
The National Comprehensive Cancer Network recommends counting at least 500 nucleated cells on marrow smears containing spicules for accurate blast enumeration 3, 4
Myeloblasts, monoblasts, and promonocytes should be included in the blast count, as per the European Society for Medical Oncology guidelines 4
If aspirate is inadequate, a bone marrow trephine biopsy with immunohistochemistry for CD34 should be performed to assess blast burden, as recommended by the European Society for Medical Oncology 4, 5

Multiparameter flow cytometry (minimum 3-4 colors) should be performed to detect MRD using the aberrant immunophenotype established at diagnosis, according to the National Comprehensive Cancer Network 1, 6
Flow cytometric MRD assessment from bone marrow is recommended after treatment cycles and can detect residual disease below morphologic thresholds, as per the European Society for Medical Oncology guidelines 1
The absence of MRD correlates with better outcomes in AML patients, according to the European Society for Medical Oncology 1

Molecular MRD assessment should be performed if a molecular marker was present at diagnosis, as recommended by the European Society for Medical Oncology 1
Molecular testing can be performed from both peripheral blood and bone marrow, according to the European Society for Medical Oncology guidelines 1

Bone marrow biopsy should be performed on days 21-28 of each venetoclax cycle for response assessment, as recommended by the National Comprehensive Cancer Network 2
If morphologic remission is achieved and counts recover, subsequent bone marrow biopsies can be repeated at 3-6 month intervals, according to the National Comprehensive Cancer Network guidelines 2
If blood counts worsen over time despite prior remission, repeat bone marrow biopsy immediately to rule out relapsed disease before stopping therapy, as recommended by the National Comprehensive Cancer Network 2

Complete blood count with differential should be performed to assess peripheral blast count and cytopenias, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 1, 7
Comprehensive metabolic panel should be performed to evaluate organ function, according to the National Comprehensive Cancer Network guidelines 7

Peripheral blood counts should not be relied upon solely to determine disease status, as bone marrow assessment is essential even when peripheral counts appear normal, as per the European Society for Medical Oncology guidelines 1
Flow cytometric CD34 counts should not be used as a substitute for visual blast assessment, as not all blasts express CD34 and processing artifacts can cause errors, according to the European Society for Medical Oncology 5
Venetoclax should not be stopped based on cytopenias alone without confirming disease status, as prolonged cytopenias can occur even in morphologic remission with venetoclax-based therapy, as recommended by the National Comprehensive Cancer Network 2