Imatinib Therapy Improves Chronic Myelogenous Leukemia Survival Rates

A little over 10 percent of all new leukemia cases are chronic myelogenous leukemia (CML). This type of cancer starts in your bone marrow’s blood-forming cells and invades your blood. During 2014 in the U.S., the American Cancer Society estimates doctors will diagnose about 5980 new cases, 3130 in men and 2850 in women. The average person’s lifetime risk of getting CML is about one in 588. This disease is slightly more common in men than in women and affects more whites than African-Americans. While the average age of CML diagnosis is around 64, almost half of new patients are 65 and older. Previous research associates chronic myeloid leukemia with the Philadelphia chromosome, a translocation of chromosomes 9 and 22. The resulting gene fusion creates the problematic BCR-ABL1 protein product. This constitutively active, growth-promoting tyrosine kinase contributes to the malignant transformation of cells. CML incidence has grown slightly over the past 10 years, but the advent of targeted therapies has increased survival greatly. Since the introduction of Imatinib, the first small molecule BCR-ABL1 inhibitor, this and other tyrosine kinase inhibitors (TKIs) have revolutionized CML treatment. These drugs are capable of targeting cancer and blocking BCR-ABL1 activity, the principle driver of chronic myelogenous leukemia, without harming normal cells. So today, the previously expected five-year survival rate for newly diagnosed CML patients has nearly doubled.

What to Expect With CML

Chronic myelogenous leukemia occurs when something goes awry in your blood cells’ genes. Any blood-forming or lymphoid cells can turn into leukemia cells. This aberration prevents the normal maturing process. Cells may reproduce too quickly, and in most cases, leukemia cells don’t die when they should. They survive and build up, crowding out normal bone marrow cells. At some point, leukemia cells spill into your bloodstream. This can lead to low normal blood cell counts. Generally, these cells don’t fight infection as well as normal white blood cells. Eventually, the cells also can invade organs including the spleen, where they can prevent other cells from working properly. CML also can change into a fast-growing acute leukemia that invades almost any organ in the body. Because leukemia cells tend to build up over time, many people don’t experience any symptoms for at least a few years. Signs and symptoms of chronic myelogenous leukemia may include:

• Easy bleeding
• Feeling run down or tired
• Fever
• Weight loss without trying
• Loss of appetite
• Pain or fullness below the ribs on the left side
• Pale skin
• Excessive night sweats during sleep

Powerful Prescription Remains the Standard Treatment

Seeing your doctor for chronic myelogenous leukemia diagnosis and treatment as early as possible can improve your prognosis. The TKI Gleevec (Imatinib Mesylate) was the first molecule of its kind that research showed to be highly effective in Philadelphia-chromosome-positive chronic myeloid leukemia. The introduction of this agent improved the standard of care dramatically over older systemic first-line therapies. By killing CML cells without harming normal ones, Imatinib improves your chances of experiencing a favorable outcome.

CML Remission Rates Rise Dramatically

A showed that most chronic myeloid leukemia patients experienced a deep molecular response to the Imatinib TKI medication. This achievement predicted their outcomes would be better than complete cytogenetic response (CCR). It also added years to their lives and increased their survival rates significantly. From a study cohort of 1551 randomized patients, 1524 were evaluable and included in the final analysis. Researchers defined deep molecular response as at least a 4.5 log reduction in BCR-ABL1 on the international scale (MR^4.5). The cumulative MR^4.5 incidence after nine years was 70 percent with a median of 4.9 years to reach this milestone. Patients attained this deeper response more quickly with an optimized higher Imatinib dose of 800 milligrams per day over the more standard 400 milligrams per day (48 vs. 62 months; P = 0.016). In the full cohort, the five-year overall survival rate was 90 percent. The five-year progression-free survival was 87.5 percent, and the eight-year overall survival was 86 percent. Regardless of which Imatinib dosage patients used, achieving MR^4.5 at four years predicted higher survival probability than CCR (eight-year overall survival, 92 percent vs. 83 percent; P = 0.047). Investigators identified both higher Imatinib dosages and early major molecular remission as independent MR^4.5 predictors. The lead researcher determined that the majority of CML patients can achieve very deep remissions with Imatinib. This suggests that deep molecular response is a precondition for CML treatment discontinuation, which also resolves the cost and compliance factors of ongoing pharmaceutical therapy. Because Imatinib’s impressive success raised the average survival duration dramatically, investigators concluded that doctors and patients should consider MR^4.5 a new predictor of long-term survival.

Forecasting an Optimist Future

According to , M.D., director of the Oregon Health and Science University Knight Cancer Institute, Imatinib has changed the chronic myeloid leukemia prognosis from three to five years to living a normal lifespan. He attributes the successful journey to researchers developing the first solution by understanding what drives this cancer’s growth. That led to additional drugs to treat CML. Dr. Druker has patients who are living proof that TKI prescription medications can make surviving and thriving for 20 years after CML diagnosis possible. Coupled with the recent massive strides in research, he foresees a brighter, longer future for CML patients.