The Case for Laboratory Developed Procedures: Quality and Positive Impact on Patient Care

Kaul, Karen L.; Sabatini, Linda M.; Tsongalis, Gregory J.; Caliendo, Angela M.; Olsen, Randall J.; Ashwood, Edward R.; Bale, Sherri; Benirschke, Robert; Carlow, Dean; Funke, Birgit H.; Grody, Wayne W.; Hayden, Randall T.; Hegde, Madhuri; Lyon, Elaine; Murata, Kazunori; Pessin, Melissa; Press, Richard D.; Thomson, Richard B.

No other LDP in the field of oncology has had a greater impact on patient care than has the quantitation of RNA in chronic myelogenous leukemia (CML). One of the first (and arguably most successful) molecularly targeted cancer therapies is the BCR-ABL1-targeted tyrosine kinase inhibitor, imatinib, which was FDAapproved in 2001. In those very early days of targeted therapy, long before the advent of FDA-approved "companion diagnostics," the ubiquitous and obvious method to determine the efficacy of novel leukemia treatments was to directly quantitate the target of the inhibitor drug, namely, the cancer cellspecific BCR-ABL1 fusion gene. A reduction in posttreatment BCR-ABL1 RNA levels, as measured by sensitive laboratorydeveloped PCR-based methods, was shown to be the best available test for predicting therapeutic response and long-term progression-free survival in TKI-treated patients with CML. 89 Consensus oncology practice guidelines in both the United States (NCCN) 90 and Europe (ELN), 91 going back at least a decade, have universally recommended that TKI-treated patients with CML should be serially monitored with a (laboratory-developed) BCR-ABL1 RT-PCR blood test at least every 3 to 6 months during their lifelong course of TKI therapy. The NCCN and ELN guidelines have also long recommended serial BCR-ABL1 RNA testing to directly inform not only the appropriate dose of TKI (to overcome developing resistance) but also the therapeutic switch from one TKI to another (depending on the drug's known resistance profile).