Treatment Response

Unless clinical trials include head-to-head comparisons, determining the relative efficacy of acute myeloid leukemia (AML) treatments is challenging. One study may have distinctly different patient populations based on age or type of AML, varying drug doses, and may use different procedures. In 2003, the International Working Group (IWG) developed a set of recommendations to standardize response criteria in AML clinical trials.1

IWG Response Criteria in AML1a

Response Criteria Time of
Assessment
Neutrophils (μL) Platelets (μL) BM Blasts (%) Other
Early treatment assessment 7-10 days after therapy NA NA <5
Morphological leukemia-free state Varies by protocol NA NA <5 Flow cytometry EMD
Morphological CRa Varies by protocol >1000 >100,000 <5 Transfusion EMD
Cytogenetic CR Varies by protocol >1000 >100,000 <5 Cytogenics
—normal, EMD
Molecular CR Varies by protocol >1000 >100,000 <5 Molecular
—negative, EMD
PR Varies by protocol >1000 >100,000 >50 or decrease to 5-25 Blasts
<5% if Auer rod positive
aAll criteria should be fulfilled; marrow evaluation should be based on a count of 200 nucleated cells in an aspirate with spicules.
BM, bone marrow; CR, complete response; EMD, extramedullary disease; PR, partial remission.

 

Additional Responses in AML2

Category Definition
Transfusion Independence
RBC No transfusion for 56 consecutive days on-study for patients who were transfusion dependent at baseline (≥1 transfusion in the 56 days before study start) and patients who were transfusion independent at baseline and remained transfusion independent
Platelets No transfusion for 56 consecutive days on-study for patients who were transfusion dependent at baseline (≥1 transfusion in the 56 days before study start) and patients who were transfusion independent at baseline and remained transfusion independent
Other
Stable disease Not meeting criteria for any other treatment response: CR, CRi, PR, disease progression, or treatment failure (ie, early death)
aPretreatment counts averages of at least 2 measurements (not influenced by transfusions) ≥ 1 week apart (modification).
bModification to IWG response criteria.
CRi, complete response with incomplete hematologic recovery; Hgb, hemoglobin; RBC, red blood cells.

References: 1. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642-4649. 2. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291-299.