Evaluating Sensitivity of ipsogen BCR-ABL1 Mbcr IS-MMR DX Kit for Scoring Molecular Response

Objective: Tyrosine kinase inhibitors (TKIs) are the standard of care for patients with chronic myeloid leukemia (CML). Recent studies demonstrated that some patients with CML could sustain remission under discontinuation of TKIs. The clinical decision to discontinue such therapy depends on the patient’s molecular response (MR), derived from the international scale of BCR-ABL1 transcripts per internal control gene transcripts (BCR-ABL1IS), with MR4.5 (i.e., BCR-ABL1IS ≤0.0032%) commonly used as a threshold for discontinuation of TKI. However, it remains controversial whether all methods for determining BCR-ABL1IS have sufficient sensitivity for measuring MR4.5. Methods: Probit analysis with reference to CLSI EP-17-A2 was used for the kit-specific limit of detection (LoD) of BCR-ABL1 transcripts measured by the ipsogen BCR-ABL1 Mbcr IS-MMR DX Kit. In total, 50 samples of peripheral blood (PB) were collected from CML patients across three sites, with each 21-ml sample split into 7- and 14-ml volumes. Results: The kit-specific LoD was determined as 3 copies/assay. The sample measurements of 94% (7-ml PB group) and 96% (14-ml PB group) showed over 94 000 copies/assay of ABL1 transcripts, which is the level required to score MR4.5 considering kit-specific LoD of 3 copies/assay. Conclusion: This result demonstrated that the ipsogen BCR-ABL1 Mbcr IS-MMR DX Kit possesses sufficient sensitivity for stable scoring at MR4.5, with strict conditions set for avoiding false-negative results.