Two new-generation drugs may soon replace the agent that revolutionized the therapy of patients with chronic myeloid leukemia, i.e. imatinib (Glivec), according to hematologists based on the results of the latest research.
They are dasatinib and nilotinib, which belong to the second generation of bcr-abl tyrosine kinase inhibitors, a protein that stimulates the development of chronic myeloid leukemia (CML).
In June 2010, the US Food and Drug Administration (FDA) approved nilotinib (trade name Tasigna) as the first-line treatment for recently diagnosed CML based on studies that showed that, compared to imatinib, it responds faster in more patients.
In turn, evidence of the superiority of dasatinib (trade name Sprycel) over imatinib was presented in mid-June at the 15th Congress of the European Society of Hematology (EHA) in Barcelona. The week before, they were also presented at the 46th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The drug may be approved in the first line of CML therapy in the coming months.
Chronic myeloid leukemia is a cancer that originates in the stem cells of the bone marrow. Its development occurs as a result of a genetic aberration, which is the transfer of a fragment of chromosome 9 to chromosome 22. The result is the formation of the so-called. Philadelphia chromosome and the BCR-ABL fusion gene located on it (a fusion of the BCR gene from chromosome 22 with the ABL gene from chromosome 9). The protein contained in it has tyrosine kinase activity, which constantly stimulates the division of bone marrow stem cells.
Most people between the ages of 50 and 60 develop CML. There are three phases in the natural course of the disease: the chronic phase, which lasts about 3-4 years; an acceleration phase, which accelerates the production of abnormal bone marrow cells; and a blast crisis phase (blast crisis), which resembles acute leukemia and is characterized by a significant increase in the number of these cells.
The only cure for CML is a donor bone marrow transplant. However, the condition is – in addition to the availability of the donor – good health, which is why it can be used primarily by younger patients. Moreover, this procedure carries a high risk of complications.
Even 10 years ago, when CML was treated with cytostatics, after 3-4 years there was an acceleration phase or a blast crisis, and then there was no rescue for the patient. Therefore, the patients lived on average 4-5 years, told PAP Prof. Andrzej Hellmann, head of the Department and Clinic of Hematology and Transplantology at the Medical University of Gdańsk.
As he recalled, the introduction of imatinib (Glivec) in 2001 revolutionized the treatment of this disease and prolonged patients’ survival.
Imatinib is an inhibitor of the bcr-abl kinase, which means that it blocks its activity. Its effect is to stop the division of bone marrow stem cells and intensify the processes of their suicidal death (apoptosis).
In 2007 and 2008, new generation bcr-abl kinase inhibitors appeared, which are included in the second line of therapy in patients for whom imatinib does not work or is not tolerated. Currently, these are two drugs – dasatinib or nilotinib.
As assessed by prof. Agnes Buzyn of Hopital Necker in Paris at the media meeting at the 15th EHA Congress in Barcelona, thanks to these three drugs CML has become a chronic disease and patients can live with it for over 20 years.
However, about 15 percent. in patients, the drug does not induce a response and does not protect against blast orthosis. Therefore, there was a hypothesis that in this group the use of newer drugs immediately, in the first line of treatment, would give better results – explained Prof. Hellmann.
Clinical studies have confirmed that both nilotinib and dasatinib actually respond faster in more patients than with imatinib.
Two types of response to the drug were assessed – cytogenetic remission, i.e. a reduction in the number of marrow cells containing the Philadelphia chromosome, and molecular remission, which is a more sensitive method of testing response to therapy and indicates a greater reduction of these cells.
Previous studies show that patients who achieve cytogenetic remission in less than a year from the start of therapy are less likely to experience rapid progression of the disease to the blast phase – reminded Prof. Michele Baccarani from the University of Bologna. As he added, in the case of imatinib, as much as 30-40 percent. patients do not have such a response until one year.
In the latest study, which included a total of 519 patients with recently diagnosed CML in the chronic phase, 77% achieved cytogenetic remission by the end of the year. patients in the dasatinib group. In 54 percent Patients responded very quickly to the newer drug – cytogenetic remission was observed within 3 months. Patients treated with dasatinib also had molecular remission more often.
According to prof. Baccarani, the results of these studies may lead to a change in standards in the treatment of chronic myeloid leukemia in the future.
I do not think that the guidelines for the treatment of chronic phase CML will change significantly in 2010, but it can be expected that soon in patients, especially those with a higher risk of disease progression – that is, in approx. 30 percent. patients – it will be possible to use second-line drugs right away – assessed prof. Hellmann.
As he recalled, economic considerations are of great importance here. If the treatment of chronic myeloid leukemia were to become significantly more expensive, it is known that the budgets of many countries, even the richest ones, will not be able to withstand it, the hematologist noted.
However, there is some hope that the use of newer first-line drugs could lead to a full recovery after a few years, so the patient would not have to take the drug for life, as in the case of imatinib, the specialist explained. Then it could also turn out to be more economical for the budget.
However, the results of the research that will verify these hypotheses still have to be waited for a while – he emphasized. (PAP)