Comparison of molecular responses based on BCR-ABL1%IS results from an in-house TaqMan-based qPCR versus Xpert® assay in CML patients on tyrosine kinase inhibitor therapy

Objectives: Tyrosine kinase inhibitors (TKIs) have drastically changed the prospects for chronic myeloid leukemia (CML) patients. The European LeukemiaNet (ELN) recommends molecular monitoring of BCR-ABL1 mRNA levels at distinct time points to define an optimal response, warning, or failure of treatment. Methods: Sixty-four follow-up peripheral blood samples from CML patients on TKI were tested by two methods. Molecular responses based on BCR-ABL1%(IS) from an Xpert (R) BCR-ABL1 Monitor assay were compared with TaqMan-based qPCR. Results: Seven samples showed 'molecularly undetectable leukaemia' by both methods (11%). In-house qPCR showed 57 BCR-ABL1+ samples; 45/57 samples (79%) were concordant for 'major molecular response' (MMR, n=32) and 'no MMR' (n=13) by both assays, whereas nine were BCR-ABL1 negative by Xpert (R). Identical molecular responses (i.e. 'optimal') were defined in 41 samples. Discordances seen in patients <10 months on TKI (n=2) had no impact on clinical management, whereas for patients >12 months on TKI, a different molecular response was defined ('warning' versus 'optimal'). Thirteen samples had 'no MMR' by both methods. 10/13 showed identical intervals (>10%(IS), 1-10%(IS) or 0.1-1%(IS)), corresponding to seven 'failures' and three 'warnings'. Discordant intervals were seen in 3/13 samples (all defined as 'failures'). Deep molecular responses (MR4.0 or MR5.0) with detectable BCR-ABL1 showed some fluctuations between both methods, nevertheless, all had 'optimal' responses. 'Molecularly undetectable leukaemia' was observed more frequently by Xpert (R) (n=16) as by our in-house assay (n=7). Discussion: Based on current ELN recommendations, Xpert (R) BCR-ABL1 assay defines identical molecular responses as TaqMan-based qPCR BCR-ABL1%(IS) data in 98% (63/64) of samples.