After being diagnosed with chronic myelogenous leukemia, you and your doctor will need to make some decisions about the treatments you’ll need to keep your disease under control. The following are some of the most important questions about CML medications and how medical research has answered them.
1. Does treatment work?
The most common medication used to treat CML is Gleevec (imatinib), which interrupts the abnormal signals that cause your white blood cells (WBC) to multiple in an uncontrolled way. In a 6-year study of people taking Gleevec, only 5% died of their leukemia (Castagnetti and colleagues. Leukemia 2015;29:1823-1831). In fact, slightly more people (6%) in this group of older individuals died due to other causes. This shows that if your CML is well controlled, you have a very good chance of living a normal lifespan.
2. What if treatment doesn’t work?
In the study mentioned above, some people lost their response to Gleevec and were switched to a more potent medication – either Tasigna (nilotinib) or Sprycel (dasatinib). This idea of switching people who aren’t getting the most from their treatment was examined in the TIDEL-II study (Yeung and colleagues. Blood 2015;125:915-923). People started with a high dose of Gleevec, and their response to the medication was assessed every three months. Anyone failing to achieve an optimal response was quickly switched either to an even higher dose of Gleevec or to Tasigna. At the end of the 3-year study, overall survival was 96%, demonstrating that tailoring the intensity of treatment according to your needs is an effective strategy.
3. If there are more potent medications, why not start with one of them?
The goal of treatment is to shut down the signals (called BCR-ABL transcripts) causing your WBCs to proliferate, and Tasigna and Sprycel can do this more rapidly than Gleevec. So either of these medications can be taken first instead of starting with Gleevec.
What will this achieve? In the ENESTnd study, people starting with Tasigna were almost twice as likely to achieve a major molecular response (MMR) in the first two years compared to those starting with Gleevec (71% vs. 44%) (Kantarjian and colleagues. Lancet Oncol 2011;12:841-851). Indeed, leukemia signals were essentially undetectable in 21-26% of people taking Tasigna compared to 10% taking Gleevec. After five years, most people (52-54%) on Tasigna had an undetectable level of CML (a 4.5-log reduction or better) compared to 31% of those in the Gleevec group (Hochhaus and colleagues. Leukemia 2016; epublished February 3, 2016).
Similar results were seen in the DASISION trial comparing Sprycel and Gleevec (Jabbour and colleagues. Blood 2014;123:494-500). After three years of treatment, 69% achieved an MMR with Sprycel compared to 55% with Gleevec. And leukemia was undetectable in 22% of people in the Sprycel group compared to 12% in the Gleevec group.
4. Is it better to have a quicker response?
The current benchmark for evaluating a person’s response to medication is a 1-log reduction in BCR-ABL transcripts within the first three months of treatment. A “1-log reduction” means that leukemia signalling is reduced to less than 10% of what it had been before. Why the need for speed? This was examined by the German CML Study Group, which looked at long-term outcomes according to the person’s early response (Hanfstein and colleagues. Leukemia 2012;26:2096-2102). The overall survival at 5 years for people achieving a 1-log reduction was 94%. For those who didn’t achieve this milestone, the 5-year survival was 87%.
It has even been suggested that the rate at which BCR-ABL transcripts are reduced by one-half (i.e. from 100% to 50% to 25%, etc.) is important (Branford and colleagues. Blood 2014;124:511-518). The study looked at people who didn’t achieve a 1-log reduction. If the “halving time” was fewer than 76 days, the person did much better than those with a longer halving time (95% survival at 4 years compared to 58% survival).
5. Is it really necessary to have frequent tests?
The need for frequent tests of blood and bone marrow is an unfortunate reality, but testing ensures that you are responding to treatment. A lot can happen in the interval between tests, and it’s important that any decisions about the type or intensity of your treatment regimen are made quickly. If your treatment isn’t working, something needs to be done before your CML gets out of control. This was shown in a study of 38 medical practices in the U.S. (Goldberg and colleagues. Curr Med Res Opin 2013;29:1075-1082). In almost all cases in which CML progressed or an individual died, the person had not undergone regular testing. One or two tests per year was acceptable; but 3-4 tests resulted in the best outcomes.
6. Do I need to take my CML medication every day?
Cancer treatments have traditionally been injectable drugs administered in a hospital. CML medications avoid this inconvenience. They are pills that you take in the comfort in your own home. But that means there’s no medical supervision, and the onus is on you to remember to take your medication. Missing one or two pills doesn’t seem like much, but being cavalier about treatment does have consequences (CML is a type of cancer after all).
This was demonstrated in a study looking at whether sticking to the program had an impact on outcomes (Marin and colleagues. J Clin Oncol 2010;28:2381-2388). Over a 6-year period, there was a substantial difference between those who took 90% of their pills and those who took less than 90%. If you took at least 90% of your pills, the probability of achieving MMR (a 3-log reduction) was about 95%. If you fell below the 90% mark, the probability plummeted to 28%. This 90% mark represents a mere 3 days a month. If you miss taking your medication more than 3 days a month, you risk not having an excellent treatment response. Among those who forgot to take their treatment on 6 days a month (80%), 0% – no one – achieved a molecular response. Taking a “drug holiday” for a couple of weekends a month is enough to jeopardize the entire regimen. CML doesn’t take holidays, so it critical that you do what you can to keep it under control every day.