Dana-Farber Cancer Institute recently partnered with CancerConnect so that patients could ask Marlise Luskin, MD, MSCE, their questions about chronic myelogenous leukemia (CML). Dr. Luskin is a physician in the Adult Leukemia Program at Dana-Farber and an instructor in Medicine at Harvard Medical School. Her areas of expertise are adult leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms. You can find patients' questions and Dr. Luskin's answers below.
Stopping TKIs
I have read recently that some CML patients are able to stop taking a tyrosine kinase inhibitor (TKI) once in remission, is this true?
Yes, clinical trials are showing that a small portion of patients diagnosed with CML can eventually stop TKIs safely.
However, only select patients are eligible for so-called TKI "stopping trials" (discontinuation of a TKI under the supervision of a physician with close monitoring). Such patients generally have been taking TKIs for many years (5 or more), have had very deep, sustained responses for several years (4 or 5 log reductions of the BCR-ABl transcript), and generally lacked "high risk" factors at diagnosis. Among this select group, about 40-50 percent of patients can safely remain off TKI therapy over the long-term.
While this is an exciting development, it is important that patients are carefully evaluated for eligibility for a stopping trial and are monitored closely, particularly for the first 1-2 years after stopping TKI. A TKI should never be stopped without discussing with the treating physician.
Additionally, follow-up of the first patients who stopped TKIs on clinical trial is still relatively short and many oncologists are recommending that patients wait until the data is more mature before recommending TKI discontinuation under routine circumstances. This is currently an area of practice change. Speak to your treating physician if you have questions about your eligibility for a stopping trial now or in the future.
Survival Statistics and Maintenance Chemotherapy
Are there any survival statistics on patients who choose not to do maintenance chemotherapy vs. patients who do?
Patients with CML who are not treated with TKIs will almost always progress to a more aggressive, advanced phase of disease in 3-5 years. It is important to treat CML prior to progression as the more advanced phases (CML in accelerated or blast phase) are much more difficult to treat. Patients with CML in chronic phase can expect a normal life expectancy if they are treated appropriately. This is unfortunately not the case in patients with advanced phase disease.
Gleevec
I've been on Gleevec since 2005; how long until I stop using it? My oncologist advised to keep using it.
Whether imatinib (Gleevec) can be stopped is an individualized decision. I would only consider a trial of discontinuation in a patient who has had a consistent, very deep response over many years. Additionally, the follow-up data on the patients who first stopped imatinib on clinical trial is still relatively short and many oncologists are recommending that patients wait until the data is more mature before recommending TKI discontinuation under routine circumstances. In patients doing well on therapy with minimal side effects, it may be reasonable to wait until longer follow-up data has accrued. I would recommend discussing with your oncologist his or her rationale for advising against it.
Is the constant feeling of being cold a side effect of Gleevec?
Feeling cold is not a typical side effect of imatinib (Gleevec), but certainly many patients describe chronic, low-level side effects related to the drug and it is possible that your feeling of being cold is related to the drug. Imatinib is also associated with thyroid dysfunction, and it would be reasonable to ask your doctor to check your thyroid levels (thyroid stimulating hormone).
Ponatinib Study
I saw a recently published study indicating that ponatinib was superior to a stem cell transplant for CML. Can you comment on this study?
A recent publication in the journal Cancer (April 7 – Epub ahead of print) describes the survival of patients with CML or ALL with a T315I mutation treated with ponatinib versus stem cell transplant. The authors describe an improvement in survival among patients with CHRONIC PHASE disease treated with ponatinib versus allo-SCT. Patients with more advanced CML (blast-crisis) had improvement in survival with transplant. Importantly, this was a retrospective study, meaning that there may be some factors that differed between the treatment groups that cannot be accounted for.
In summary, this study and others clearly show that ponatinib is a valuable treatment option for patients with CML that is resistant to other TKIs. Whether transplant should also be considered depends on many features of the patient (age, other health problems, personal preferences, etc.) and disease. The merits of a transplant for an individual patient should be discussed with the treating oncologist.
Mini-Stem Cell Transplants
I have CMML Intermediate 1, platelet down to 601 monocytes 28.9 percent, positive Jak2, ASXL1 and 2 distinct TET2 mutations, age 79. Feel fine now. Diagnosed 3/2016. In the future is a mini-stem cell transplant a possibility?
It is important to recognize that CMML (chronic myelomonocytic leukemia) is an entirely different disease from CML despite acronyms that are very similar. Patients with CML and CMML should make sure they are reading the correct information. Transplant is generally not an option for patients over about 75 years of age.
Hydroxyurea
I am on hydroxyurea 3 times per week. Lately I have had red irritated spots under my eyes and on my chin. Could hydroxyurea cause this?
Some patients taking hydroxyurea can develop a rash or dry skin that may then be sensitive to soaps, perfumes, and moisturizers. Any new rash that is significant or persistent should be evaluated by a health care provider.
ASXL1 Mutation
Is the ASXL1 mutation a negative prognostic factor?
ASXL1 mutations are common in a variety of myelogenous malignancies (cancers). The impact of an ASXL1 mutation in patients with CML are still being studied but preliminary evidence suggests that it may be related to the development of TKI resistance/progression. However, more studies are needed and currently we do not routinely check for ASXL1 mutations or alter treatment based on the presence or absence of the mutation.
Stem Cell Transplants and CML
What determines whether or not someone with CML should consider a stem cell transplant for treatment?
This is certainly a question every patient should discuss with his or her doctor. In general, we consider transplant for CML patients with advanced phase disease or CML that has stopped responding to most or all TKIs.
New Precision Medicines
What new precision medicines are in development for the treatment of CML? Do the checkpoint inhibitors have activity in CML?
This is an excellent question. We do not yet have data on the clinical activity of checkpoint inhibitors in the treatment of CML, either alone or in combination with a TKI. Early phase studies are underway (e.g., NCT02011945).
Clinical Trials and CML
Are there any promising clinical trials in CML?
Clinical management of CML has advanced rapidly over the last two decades, in large part due to the successful completion of many clinical trials. I expect that in the next several years, clinical trials will focus on maximizing the number of patients who can achieve deep responses (and thereby be eligible for stopping therapy) as well as minimizing toxicity. Novel TKIs and other agents for CML are in development and will likely be investigated in future clinical trials, often in combination with current TKIs in clinical use. That being said, the success of current TKIs is making it an increasingly challenging endeavor to develop a new or better treatment for CML. It is a good problem to have!
Note: This Ask the Expert Q & A is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Speak to your health care provider about any questions you may have regarding your health.