Highlights from the American Society of Hematology (ASH) annual meeting, San Diego CA, December 3-6, 2016 – The annual meeting of the American Society of Hematology is the largest medical congress of the year, and featured the results of several new trials on chronic myelogenous leukemia. Here are some of this year’s highlights.
Early response with Sprycel: A new study in Japan reports that early treatment with Sprycel, a second-generation TKI, can achieve an earlier response in more people compared to Gleevec (Murai and colleagues. ASH 2016; abstract 3102). A total of 70 people with CML received Sprycel 100 mg per day. Overall, 77% achieved a major molecular response (MMR) within one year of starting treatment, and 35% achieved a 4.5-log reduction (MR4.5, i.e. undetectable disease). People older than age 62 years were more likely to reach MR4.5 compared to younger people. These results are somewhat better than what has been seen in other populations. The researchers suggested that Sprycel may induce immune effects in older Japanese people that give an added boost, but this will require further study.
Higher-efficacy treatment may “top-up” response: Many people respond well to Gleevec, achieving a major molecular response (MMR, or a 3-log reduction in BCR-ABL transcripts) within the first year or two of therapy. But can this response be improved upon by switching to a higher-efficacy medication? This issue was investigated in a new study in Japan (Shibayama and colleagues. ASH 2016; abstract 1914). People were enrolled in the study if they had achieved MMR but still had detectable residual disease. All were switched to Tasigna. After two years, 53% were able to achieve a complete molecular response (a 4.5-log reduction, or MR4.5), which meant that CML was no longer detectable. These results suggest that even people with a good response to Gleevec can achieve an even better response if they switch to a more potent medication. The chief advantage is that once you’ve reached MR4.5, you may be eligible for a “stop trial”. This will determine if your CML is well enough controlled that you no longer need to take a medication.
Targeting leukemic stem cells: TKIs have been highly successful in controlling the CML disease process. However, some leukemia cells can remain hidden in the bone marrow, out of reach of treatment. These cells have the potential to cause a relapse if they “escape” – either because of a mutation or because there isn’t enough medication to keep them suppressed. The conventional wisdom is that TKIs aren’t able to eradicate leukemic stem cells, although recent trials have suggested that some people won’t relapse even after stopping a drug. So a group of researchers looked at this issue more closely (Pungolino and colleagues. ASH 2016; abstract 3080). They collected bone-marrow samples from 87 people newly-diagnosed with CML throughout the course of treatment with Tasigna. After one year, only four people (5%) had detectable leukemic stem cells. Of these four, ione person had a treatment-resistant mutation and one was slowly losing the response. The other two people achieved a complete cytogenetic response (CCyR) despite having some residual disease. The researchers concluded that treatment with Tasigna can eradicate leukemic stem cells in most people if the medication is started early enough.
Some signalling pathways in the bone marrow may create a microenvironment that enables leukemic stem cells to survive. So a separate study looked at targeting these pathways (called JAK/STAT) with a therapy called ruxolitinib (Jakavi or Jakafi), which is used to treat other blood/bone marrow disorders (Kendra and colleagues. ASH 2016; abstract 1892). The people studied were those who were taking Tasigna for their CML and had achieved a complete cytogenetic response but still had detectable residual disease. All received add-on therapy with Jakavi for a six-month period. At the end of the study, 4 of 9 people (45%) had achieved a 4.5-log reduction (MR4.5), and 3 (33%) had a 1-log or better improvement in their response. Two people continued to have active disease. The drug combination was tolerated well, with most people reporting that their fatigue was improved with the two medications. These encouraging results are preliminary, but they suggest that adding a second treatment can significantly improve people’s response to a TKI and may help to eradicate CML.