Quotes from renowned CML experts on the cost of therapy and the need for predictive biomarkers:
This Forum reﬂects the views of a large group of CML experts who believe that the current prices of CML drugs (1) are too high, (2) are unsustainable, (3) may compromise access of needy patients to highly effective therapy, and (4) are harmful to the sustainability of our national health care systems. These concerns reﬂect the spiraling prices of cancer drugs in general. Of the 12 drugs approved by the FDA for various cancer indications in 2012, 11 were priced above $100 000 per year. Cancer drug prices have almost doubled from a decade ago, from an average of $5000 per month to >$10 000 per month.
~Experts in Chronic Myeloid Leukemia, Blood online, April 25, 2013; DOI 10.1182/blood-2013-03-490003
Patients with sustained undetectable transcripts by PCR is the cohort that would be considered potentially eligible for treatment discontinuation. You would expect that grossly half would relapse and half would not, so the biomarker should have grossly that distribution.. Patients with low levels of detectable disease (e.g., MR4) either sustained while on therapy or who have relapsed after treatment discontinuation but still at low levels. You would expect that most of these patients would express the biomarker.. Patients that have discontinued therapy and have not relapsed, ideally after at least 6 months. The risk of relapse after 6 months is low so you would expect that none or not more than very few would express the biomarker.
~Jorge Cortes, M.D. at MD Anderson Cancer Center. 01.04.2017
It has been observed in clinical trials that molecular recurrence occurs in about half of the patients who stopped TKI after having reached a deep molecular response (DMR, based on very low or undetectable BCR-ABL, i.e. 4 log or greater reduction). Factors predicting recurrence are currently lacking, with more patients having to take a 2G-TKI to reach the goal of DMR for TKI discontinuation, though successful discontinuation is also possible on IM.
~agreed by Michael Deininger, M.D. at Huntsman Cancer Institute. 01.06.2017
Importantly, patients with longer and deeper molecular responses are thought of now as potentially cured. Unfortunately, clinical trials have shown that about half of these patients relapse after cessation of TKIs. At this time, this is not recommended strategy for these patients unless on a clinical trial. There is as yet no good biomarker to predict those 50% of patients who will or will not relapse.. The discontinuation strategy also brings up the importance of the initial treatment choice. The second-generation TKIs, which have higher chances of achieving a deeper response might emerge as the preferred choice. Apart from the traditional biomarkers (PCR for BCR/ABL), we need novel biomarkers that can predict long-term remission/cure for these patients for TKI discontinuation. In addition, targeting CML stem cells could also emerge as a “curative” strategy.
~Amitkumar Mehta, M.D. at University of Birmingham, Alabama, ASCO Reading Room. 01.25.2017