Venetoclax for Leukemia

There are a significant number of patients who do not meet criteria for cure of their leukemia. The disease remains with many patients as an asymptomatic chronic disease in the absence of treatment.

In 2011, nearly 6 people in the United States are diagnosed with leukemia each day. The number of people diagnosed with leukemia is a lot higher in the Southern part of the country. This information is useful to anyone looking for treatment options, since they are not available everywhere. The most common type of leukemia in adults is acute lymphoblastic leukemia (ALL).

There is a high rate of anemia, thrombocytopenia, and pancytopenia among patients with leukemia. A routine use of routine hematological counts during the pre-treatment consultation is strongly advocated.

Leukemia can result from genetic abnormalities, including chromosomal rearrangements and non-rearranged chromosome translocations, as well as ionizing radiation and chemicals. Infection with the JC virus in particular has been found to be a significant risk factor for the development of acute myeloid leukemia. The development of leukemia is also linked to other health conditions such as alcoholism, a history of childhood leukemia and exposure to ionizing radiation. A number of genetic mutations and rearrangements have been associated with the development of chronic myeloid leukemia.

Leukemia is a very dangerous disease with much different prognosis. This disease was named when it was first described by Richard Bright and William Halsted in 1847. What they observed in this disease was the excessive proliferation of blood cells and they noted this condition by what we now call blood smear because they found clusters of these cells. They also found that the peripheral blood cells included different number of cells, some with small size (microcytes) and other with large (macrocytes), some with immature (sideroblasts) and other with mature (polymorphs).

Leukemia is treated with chemotherapy, radiotherapy, chemotherapy and surgery. Bone marrow transplantation is an important treatment for some people. There is also no cure for leukemia.

The most frequently observed side effects associated with venetoclax were rash/mesh like or itchy, nausea, fatigue/malaise, diarrhea, and gastrointestinal perforations. Serious side effects (>10% of patients) were hyperprolactinaemia (>5 mg/dL increase), QT interval abnormal, elevated AST/ALT ratios (>2 times normal limits), leukopenia (<1000 nucleated red blood cells/μL), and elevated systolic BP (>90 mm Hg), and elevated creatinine (>1.5 times normal limits). There was also a very rare but serious case of thromboembolism.

Results from a recent clinical trial, familial occurrence of all forms of leukemia was not found, but the risk of ALL and CLL in siblings of ALL and CLL patients is not eliminated. Therefore, hereditary factors are probably important; however, it is also possible that environmental exposures influence these diseases.

The safety and efficacy data from early clinical trials of the novel BH3 mimetic MK-8041 are promising for the future use of this drug in the treatment of B-cell Chronic Lymphocytic Leukemia (CLL). This suggests venetoclax may be useful for patients in the initial stages of CLL that are not fit for standard therapies and warrant earlier clinical trials.

Venetoclax's clinical profile showed efficacy and safety, and showed a unique effect for the targeted therapy of CLL, and more specifically in SLL patients and in relapsed SLL patients.

In a recent study, findings support the use of venetoclax as a second-line therapy for treating newly diagnosed/refractory systemic juvenile myelomonocytic leukaemia (JML) and previously treated acute myelogenous leukaemia (AML) and show that venetoclax has a significant impact on HRQoL compared with that seen in the general population.