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Subspecialties Oncology, Biochemistry and molecular biology, Precision medicine

Maintaining Molecular Remission

Chronic myeloid leukemia (CML) is a rare, but treatable, form of cancer. Once, the diagnosis forecasted death within approximately six years; now, most patients have a normal life expectancy thanks to a class of drugs called tyrosine kinase inhibitors (TKIs) (1). However, TKIs are expensive and produce a constellation of severe side effects such as chronic diarrhea, fatigue, and depression that can impair quality of life (2,3). As a result, patients are often eager to stop treatment as soon as possible. Fortunately, new data reveals that diagnostic tests powered by droplet digital PCR (ddPCR) platforms can help determine which patients may be ready to successfully discontinue TKI treatment.

The gold standard diagnostic tool for monitoring trace cancer levels in patients with CML is qPCR. Patients who experience a sustained deep molecular response (DMR), measured using qPCR technology, are eligible to discontinue treatment and begin a phase known as treatment-free remission (TFR). However, cancer will recur in about 50 percent of these patients, which requires them to reinitiate therapy (4).

In the largest prospective US-only TKI discontinuation study to date, my colleagues and I evaluated the safety of discontinuing TKI treatment based on the diagnostic tools available today. We used qPCR and ddPCR to monitor recurrence in 173 CML patients by tracking BCR-ABL1 gene expression – the primary molecular biomarker for CML – in blood samples as individuals were taken off TKI therapy (5). In 87 patients, BCR-ABL1 was undetectable using both methods; only 10.3 percent of these patients developed molecular recurrence. Meanwhile, in 56 patients, ddPCR detected measurable BCR-ABL1 expression when qPCR did not; 64.3 percent of these individuals developed molecular recurrence. We also found that discontinuing TKI treatment led to significant reductions in common TKI side effects – 80.4 percent of patients who discontinued treatment and remained cancer-free felt less fatigued, 87.5 percent experienced less diarrhea, 34.8 felt less depressed, and 21.4 percent slept better.

Overall, these data indicate that people with CML can safely discontinue TKI treatment after achieving sustained DMR as long as their molecular biomarker levels are closely monitored. Further, utilizing a highly sensitive BCR-ABL1 testing platform can increase the predictive power of biomarker testing and bolster physician confidence when discontinuing TKI treatment in qualified patients.

Hero and Teaser image credit: Paulo Henrique Orlandi Mourao (CC BY-SA 3.0).

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  1. H Bower et al., “Life expectancy of patients with chronic myeloid leukemia approaches life expectancy of the general population,” J Clin Oncol, 34, 2851 (2016). PMID: 27325849.
  2. R Kishore Narra et al., “Chronic myeloid leukemia- the promise of tyrosine kinase inhibitors,” Curr Hematol Malig Rep, 12, 415 (2018). PMID: 28944397.
  3. Leukemia and Lymphoma Society, “CML side effects.” Available at: https://bit.ly/3jXw1IA.
  4. E Atallah, K Sweet, “Treatment-free remission: the new goal for CML therapy,” Curr Hematol Malig Rep, 16, 433 (2021). PMID: 34618317.
  5. E Atallah et al., “Assessment of outcomes after stopping tyrosine kinase inhibitors among patients with chronic myeloid leukemia: a non-randomized clinical trial,” JAMA Onc, 1, 42 (2021). PMID: 33180106.
About the Author
Ehab Atallah

Professor of Medicine and Section Head of Hematological Malignancies, Medical College of Wisconsin Division of Hematology and Oncology and Froedtert Hospital, Milwaukee, Wisconsin, USA.

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