Depending on the individual laboratory, clinical transcript analysis of BCR-ABL does not always delve deeply enough to pick up patients with e13a2, e14a2, or a mixture of both. However, some labs are currently able to do this and others may be able to change their detection strategies without too much of an overhaul if this deeper transcript analysis proves clinically useful.
“My sense is this could be done quite readily and would be practical logistically. With some systems and assays currently being performed, it could mean simply reporting more detailed data from the output. In other labs, it may mean changing to more specific ‘primers’or assays to be able to quantify the different splice forms,” said Michael J. Mauro,MD, leader of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, New York, New York.
If this more detailed transcript analysis can be implemented in more centers, it could be used to help patients and their care teams decide when to attempt stopping or reducing TKI therapy.However, these conversations are complex and have to take into account a number of factors that are not as quantifiable as transcript analysis, such as patient experience of TKI toxicity and understanding of the risks involved in stopping or pausing treatment.
“We cannot exclude patients from discontinuation of TKI based on transcript alone. What we can maybe say is that we can more closely monitor these patients over the first 6–12 months, which is generally the most crucial period for loss of treatment remission. Further studies are needed to find out more about how transcripts influence sustained molecular response and the chance of successfully stopping TKI treatment thereafter,”said Dr Farina.
Both Drs Farina and Mauro stress the importance of replicating this result in further studies of other patient populations, but if this more detailed transcript analysis can be commonly integrated into existing analytical techniques, both physicians think this could establish a case for including it in treatment decision-making processes for patients with .
“As we have several TKIs and often, patient-specific stratification and treatment decision making, I would hope for an evolution in the field where TKI choice, response optimization, and counseling, decision making and execution of treatment-free–response incorporates fusion type (e13 versus e14) and any other available data,” said Dr Mauro.
- D’Adda M, Farina M, Schieppati F, et al. The e13a2 BCR-ABL transcript negatively affects sustained deep molecular response and the achievement of treatment-free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors [published online February 1, 2019]. Cancer. doi: 10.1002/cncr.31977
- Baccarani M, Gugliotta G, Castagnetti F, Soverini S, Rosti G. A review and an update of European LeukemiaNet recommendations for the management of chronic myeloid leukemia. In: Hehlmann, Ed. Hematologic Malignancies: Chronic Myeloid Leukemia. Switzerland: Springer International Publishing; 2016:55-69.