The 2017 American Society of Clinical Oncology (ASCO) Annual Meeting is taking place June 2–6 in Chicago.
At the CML Education Session, CML expert Dr. Ehab Atallah, MD, associate professor of medicine in the division of hematology and oncology at the Medical College of Wisconsin, has been speaking during an Education Session about discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia (CML) presenting about the "Promise of stopping TKIs: Is it ready for prime time"?
Even though no new data was presented (see ASH 2016 Report), it has been very interesting to listen to the US perspective.
ASCO 2017
ASCO CML Education Session 2017 CML Patient Advocates Report
The newest revision of the NCCN CML guidelines was the first treatment recommendation providing guidance on stopping treatment out in the field, which came quite out of surprise given the evidence base for providing this recommendations is still relatively thin.
In his summary, Dr. Atallah said that stopping TKIs is "ready for prime time" (in American terms, this means, ready for general use outside of trials) for a select group of patients who arefollowed up with proper monitoring in a multi-team approach.
However, he said that with about 30-50% of patients ever reaching stable MR4.5, and therapy-free remission rates of 37-63% inthe well-known discontinuation studies (STIM, TWISTER, KIDS, EuroSKI, DasFree, ENESTfreedom), only 20-30% of newly diagnosed CML patients will ever be successful in stopping current TKI therapies, while 70-80% will need long-term TKI treatment.
Therefore, the continued search for a cure should be a priority, e.g. by the US-based "Jean Khoury Cure CML Consortium" that was recently formed. This is not only needed to serve patients to get off therapy, but also from an economic perspective. In the USA, the prices for TKIs are outrageously high: Dr. Atallah quoted prices of $92.000 per year for Imatinib, $115.500 for Nilotinib, $123.500 for Dasatinib, $180.000 for Bosutinib and $348.000 for Ponatinib.
This creates challenges on two ends: first, US patients have co-pay schemes so they need to pay parts of the drug costs outof pocket, which many just can't afford. Secondly, the overall economic burden of CML is huge, given the number of CML patients in the USA is currently at 30.000 patients, but by2050, due to the good survival, will plateau at 180.000 patients in 2050.
The current annual costs of CML drugs in the USA is estimated to be 3 billion USD today - so this is clearly unsustainable even with (still expensive) TKI generics if we don't identify a cure for CML for the majority of patients soon.
Overall, the presentation has demonstrated that stopping treatment is becoming mainstream.
However, from my perspective as a patient advocate, I must say I am worried about what the average oncologist will perceive when reading the newest NCCN recommendations on stopping treatment, and the relatively relaxed way TFR is being presented at a conference like this ASCO.
I fear we may have casualties of CML patients that will leave their "safe harbor" of continuous treatment in deep molecular response if the prerequisites of frequent monitoring with highly sensitive PCR are not being met.
I feel calling for a "multi-team approach as a key component" is just not enough, and I fear patients may progress or even pass away if careless stopping, delayed re-initiation of therapy on rising PCR counts, or even "self-medicated stopping due to co-payment costs" may be happening widely out in the field.
Let's be very clear: stopping is for expert centers with best knowledge and monitoring...
Jan Geissler
CML Advocates Network cofounder
Chronic Myeloid Leukemia
also called: Chronic Myelogeneous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
Bosutinib
Bosutinib (development name SKI-606, trade name Bosulif), a second generation tyrosine kinase inhibitor.
Also called Bosulif|SKI-606|SKI606
Dasatinib
Trade name: Sprycel, development name: BMS-354825, inhibits BCR-ABL and SRC tyrosine kinases. Authorized for marketing in the EU since 2006 for the treatment of CML and Ph+ALL.
Other names: BMS-354825|BMS354825|Sprycel
Nilotinib
Trade name: Tasigna, development name: AMN107, inhibits BCR-ABL tyrosine kinase. Authorized for marketing in the EU since 2007 for the treatment of CML and Ph+ALL.
Other names: |AMN107|Tasigna
Ponatinib
Trade name: Iclusig, development name: AP24534; a third-generation tyrosine kinase inhibitor
Other names: AP24534|Iclusig.
Generics
A class of medicinal products where the drug is comparable to a branded product in dosage form, strength, route of administration, quality and efficacy, and intended use. A generic drug can only be marketed after patent exclusivity protection ends.
Imatinib
Imatinib, trade name Glivec/Gleevec, development name STI-571, a first-generation BCR-ABL tyrosine kinase inhibition. Authorized for marketing since 2002 for the treatment of CML and Ph-positive ALL.
Other names: Gleevec|Glivec
Chronic
Long-lasting, slowly developping
MR4.5
Molecular response, or molecular remission, with a reduction of 4.5 log (BCR-ABL <0,0032%)
TKIs
Tyrosine Kinase Inhibitors, a class of drugs that block an enzyme involved in the mechanism of division of cells
Gene
A unit of information present as DNA; a gene usually contains the blueprint for a protein.
CML
Chronic Myeloid Leukemia, also called Chronic Myelogenous Leukemia
A chronic disease of the blood and bone marrow that results from a transformation of a stem cell.
ASH
American Society of Hematology
MR4
Molecular response, or molecular remission, with a reduction of 4 log (BCR-ABL <0,01%)
PCR
Polymerase Chain Reaction, a very sensitive diagnostic test that allows the detection of certain genes (DNA) on a very sensitive level. PCR can detect up to one single gene in about 1 million genes.
CHR
Abbreviation for Complete Hematologic Response. The blood cell count has returned to normal, and tests don’t show any immature white blood cells. Also, the spleen has returned to a normal size if it was enlarged.
CAM
Complementary and Alternative Medicine
TFR
Abbreviation for Treatment-Free Remission. In CML is referred to having a stable deep molecular response without the need for ongoing Tyrosine Kinase Inhibitor (TKI) treatment after having been in deep molecular residual disease over a longer period of time.
