ASCO: US perspective of TKI therapy discontinuation in CML patients

ASCO17 tki discontinuation posterThe 2017 American Society of Clinical Oncology (ASCO) Annual Meeting were taking place June 2–6 in Chicago and our cofounder Jan Geissler has collected all the highlights of this important meeting for chronic myeloid leukemia community.

In the recent past, not only hematologists but also patient groups have expressed their concern that "stopping CML therapy out in the field" may lead to bad practice by doctors not following expert recommendations, and have suggested stopping TKI therapy should only be done in clinical trials.

Of course, especially after NCCN has updated its CML guideline and has given guidance on stopping treatment despite the prematurity of data, we could expect that this would be largely ignored out in the field.

So here is Jan Geissler's shock poster at #ASCO17: The high arts of CML therapy and the sad reality - we need to be grateful for investigators spelling it out so clearly. He is shocked, as his gut feeling about bad practice is now supported by data.


ASCO 2017: US perspective of TKI therapy discontinuation in CML patients report


In a poster presented by US clinicians (Ellen K Ritchie from Cornell University, New York), the results of a survey of 300 clinicians in various practice settings (community and academic) were presented. 300 clinicians all across the USA were recruited from an existing panel of physicians. The respondents had to be specialized in hematology/oncology and had to have at least one CML patient. About half of the physicians who responded were from a large practice of 10 or more physicians and have been practicing for more than 10 years.

The survey data said only about half of the doctors would always test for molecular response (which is recommended by guidelines), because the rest thought they testing for cytogenetics would be sufficient (18%) and that the cost was too high for the patient (18%). Co-pay = bad monitoring...?

Now, TKI discontinuation. 102 of the 300 physicians reported that they had attempted therapy-free remission, of whom 66 did so outside of clinical trials. This subgroup was then further assessed. Now the sad truth: there was a total disregard of expert recommendations, minimum requirements, and precautions that have been communicated by STOP study experts on all ASH and EHA meetings in the past couple of years.

As a reason for discontinuation, 76% of doctors said in the survey that adverse events were the main reason for TKI discontinuation, 47% for pregnancy planning, 35% for economic reason (20% because of high deductibles, 23% due to change in healthplan coverage), 20% due to lack of efficiency.

21% of doctors thought that a response level of MR3 (0.1% BCR-ABL) was sufficient to stop, 11% thought 2 log was sufficient, and 20% thought 1% was sufficient as minimum response. 29% thought that a response maintained for at least 3 years was sufficient, 24% thought 2 years is enough, and 20% 1 year. And in terms of minimum TKI therapy duration before stopping, 44% thought patients should have been on TKI for at least 3 years, 20% two years, and 20% for one year.

When looking at monitoring, less than 10% of physicians considered monthly molecular monitoring after stopping, and 58% thought a PCR every 3 months in the first year after TKI discontinuation was enough. 21% of doctors thought reinitiation of therapy should be at MMR (0.1%), 47% when exceeding MR2 (1% BCR-ABL) and 27% when the PCR rises above 10%. (Of note: All current TKI stop studies defined MMR (0.1%) as a criterium for re-initiation).

In summary, the authors conclude that TKI therapy discontinuation in patients with CML in chronic phase responding to TKI is happing without clear guidelines. Practice in the field largely differs from what is recommended in the NCCN guidelines.

Physicians who stop treatment to not seem to have consensus on minimum response before stopping, minimum response duration before discontinuation and frequency of CML monitoring post-discontinuation. They have no consensus on appropriate time to re-intiate treatment and on choice of treatment. This leads to a practice that results in discontinuation without first achieving the recommended deep response, combined with inadequate monitoring after stopping. The authors recommend that "recommended practice guidelines need to be communicated to physicians as TKI therapy discontinuation is likely to be conducted in a broader population."

To put it into words as a patient advocate: We are shocked that bad practice seems to be so widespread already now. Shocked that all the publications of the data from STIM, STIM2, EUROSKI and all other stop studies over the past 4 years are being ignored by oncologists who feel that premature stopping in insufficent therapy response and inconsistent monitoring after stopping is appropriate. Not to mention that stopping of treatment and inadequate monitoring seems to be driven by unique economic factors (co-pay!) of the US healthcare system.

Thank you for making this so clear. There is so much to do outside to educate doctors about guideline- und evidence-based stopping moving alongside with quality monitoring. And careless marketing for TFR will do patients that are regarded "safe" under continued therapy or who want to see their kids grow up a life-threatening disservice if the clinical requirements of stopping TKI treatment safely are not adequately met.

Jan Geissler
CML Advocates Network cofounder




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