Introduction: Chronic myelogenous leukemia (CML) is a cancer of myeloid cells that accounts for 15-20% of all cases of leukemia. Most CML cases are caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR-ABL1. The BCR-ABL1 gene expresses an abnormal tyrosine kinase protein that causes unregulated growth and survival of granulocytes. CML is treated with TKIs (tyrosine kinase inhibitors). The concentration of BCR-ABL1 transcript RNA is a marker of disease progression and the effectiveness of TKI treatment.Bio-Rad's QXDx BCR-ABL %IS Kit is an in vitro diagnostic test for the quantification of BCR-ABL transcripts in total RNA from whole blood from individuals diagnosed with Chronic Myeloid Leukemia expressing BCR-ABL1 Fusion transcript types e13a2 and/or e14a2.

Materials and Methods: The QXDx BCR-ABL %IS Kit is a newly launched FDA-approved ddPCR assay from Bio-Rad Laboratories. Reproducibility of results across multiple sites, days, instruments, and users was evaluated using contrived samples consisting of BCR-ABL positive patient samples mixed with negative patient samples. Clinical performance of the kit was evaluated on patient samples, and compared to an already existing FDA-approved test. Clinical performance was further tested in the College of American Pathologists challenge.

Results: The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The mean between the QXDx™ BCR-ABL %IS Kit and the comparator test using a Bland-Altman analysis was 0.16 MR units. The limits of agreement between the two methods indicate that the difference between the two methods should be between 0.47 and -0.14 MR on 95% of tested samples. The QXDx™ BCR-ABL %IS assay demonstrated excellent correlation with the comparator test using a Weighted Deming regression with a Pearson R correlation coefficient of 0.99, slope 1.037 and intercept of 0.1084. College of American Pathologists(CAP) challenges (n=6) were conducted from 2016-2019, QXDx™ BCR-ABL %IS system results were regressed vs the mean values published by CAP yielded a slope of 1 and R2=0.99.

Conclusions: The QXDx™ BCR-ABL %IS Kit on the QXDx™ AutoDG™ Droplet Digital PCR System can be used safely and effectively in the laboratory on t(9;22) positive CML patients for monitoring of treatment with Tyrosine Kinase Inhibitors (TKIs).

Citation Format: Dawne N. Shelton, Prasanthi Bhagavatula, Nathan Sepulveda, Lan Beppu, Jerald Radich. Performance characteristics of the first FDA-cleared droplet digital PCR (ddPCR) IVD assay for monitoring chronic myelogenous leukemia [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6483.