It’s well known that the introduction of tyrosine kinase inhibitors (TKIs, such as Gleevec, Sprycel, Tasigna and Bosulif) have significantly prolonged survival in people with chronic myelogenous leukemia. Where once a CML diagnosis meant an expected survival of only a few years, survival is now over 90% for people in chronic phase.
These survival estimates typically estimate survival over a 5-year period. But another way of looking at this issue is to examine “conditional survival”. What this does is estimate a person’s likelihood of surviving the next year.
This type of analysis has been done by researchers at the M.D. Anderson Cancer Center in Houston, Texas (Sasaki and colleagues. Cancer 2016;122:238-248). The group examined was 483 people with chronic-phase CML, with a median age of 48 years, followed up for a median of 8-9 years. Results were broken down according to how well and how quickly people responded to treatment.
For people achieving a complete cytogenetic response (CCyR, or roughly a 2-log reduction in BCR-ABL transcripts) in the first year of starting treatment, the chances of surviving the next year was 100%! As you might expect, survival was also 100% for people achieving a better level of early response, such as a major molecular response (MMR; a 3-log reduction), MR4 (a 4-log reduction), or MR4.5 (a 4.5-log reduction).
A unique aspect of the study was that the researchers also examined people later on in the treatment course. For example, if we look at people who achieved a good response (CCyR or better) in their first year of treatment and maintained it for five years, their rate of surviving the next year was also 100%. What this indicates is that once you achieve a good response, this drug effect doesn’t “wear off” if you continue to take your medication.
There is some slippage in these perfect scores over the longer term. For example, for people with early CCyR who maintain this level of response for 9 years, their likelihood of surviving the next year dipped to 96.5%. But the results were slightly better for people with a deeper early response. For those who achieved a MR4 in the first year and maintained it for 9 years, next-year survival was 98.5%. For those with MR4.5 (i.e. a 4.5-log reduction) in the first year and maintained for 9 years, their next-year survival remained at 100%.
It’s important to note that “overall survival” estimates look at all-cause mortality, not just CML-related mortality. One reason for the perfect scores was that the people studied were younger (median age was 48 years). A more typical population of people with CML is older, so next-year survival would be expected to be slightly less because of age-related risks, such as cardiovascular disease, lung disease, and other causes of death unrelated to CML.
But a further encouraging note was that the researchers also looked at a person’s chance of having a treatment failure (called failure-free survival, which included not being able to tolerate side effects), transformation to progressive CML (called transformation-free survival), or any health-related event (called event-free survival). In all cases, these rates were over 95% for every who achieved CCyR or better in their first year of treatment.
So if you’re concerned that CML treatments have allowed you to “beat the odds”, but that the odds will catch up with you, this doesn’t appear to be the case. People who achieve a good response in their first year of treatment have a near-perfect chance of enjoying the next year without anything untoward happening. But, as the researchers cautioned, this requires that the person continues to take their medication, avoids skipping doses, and sees their doctor regularly to ensure that the medication is still working.