CC-96191 for Leukemia, Myeloid, Acute

The number of new cases of leukaemia, myeloid, acute, tripled in the U.S. in 2013 and tripled again in 2017. This represents a 5.5-fold increase in incidence, the highest of any cancer in the United States. These increases are partly the result of growing use of medication to prevent and treat these blood diseases in the general population. This was a voluntary surveillance programme initiated in 1971 and continues today by the National Cancer Institute (NCI), which conducts the National Health and Nutrition Examination Survey (NHANES). The data analysed here is limited to participants age 20…80, but can be generalized by extrapolation to the population. To assess whether these increases are meaningful, ongoing surveillance is necessary.

Leukemia, myeloid, acute, is a rare type of blood disease that causes white blood cells, such as neutrophils, to grow and multiply abnormally. The cause is known most often as a mutation in the gene that gives instructions to make the receptor, called the "BCR", on the surface of white blood cells. The BCR receptor is expressed in normal white blood cells, but in this type of leukemia it is expressed in an abnormal form that does not recognize a normal set of markers on the cancer cells (such as proteins, growth factors and viruses). As a result, the abnormal cells continue to grow and multiply in the bone marrow.

Leukemia, myeloid, acute is an emergency requiring admission to the hospital. The most typical signs of leukemias are those of splenomegaly, cytopenia, and other signs and symptoms of infection. Symptoms that are less typical include a feeling of bone pain, joint pain, and abdominal pain. The symptoms are always associated to an elevated white blood cell count. Chronic lymphocytic leukemia may present with symptoms involving the mouth or throat. Symptoms typically involve the bones and may include pain with any movement or when touching a bone. Symptoms of acute myeloid leukemia may present with fever, feeling tired, and having a swollen groin, in some cases.

Leukemia occurs as a result of mutations. These mutations result from a variety of factors such as epigenetic factors, chromosomal abnormalities, infectious agents, etc. These genetic changes then lead to clonal proliferation of a cancer stem cell that expresses a specific leukemic surface marker known as a 'leukemic stem cell antigen' on its surface. The process of clone expansion in this form of leukemia is called'seminomatous leukemia', which is a type of'self-renewal leukemia'. Mutational events in these cells lead to clonal proliferation of cancer stem cells that are incapable of self-renewal, which is responsible for the development and perpetuation of the disease.

Common treatments for leukemia, myeloid, acute include chemotherapy, targeted therapy, and allogeneic stem cell transplantation. Newer treatment modalities such as targeted therapy, immunotherapy, and gene therapy are continually being tested and introduced into clinical practice.

The disease is very controllable when it is treated aggressively. However, the disease remains fatal for as many as 5 to 10% of patients who survive for a number of reasons including relapse within 2 years after therapy and in the first few years after initiation of treatment.

The effects observed herein are consistent with those found in previous studies of c-met-directed therapy which found increased survival in a subset of patients. Based on these observations and previous clinical trial data, the use of c-met antagonists seems to be a promising therapy for the treatment of MDS, though in this study, the primary treatment arm was so well-tolerated that cc-96191 was withdrawn from further testing.

In this small pilot study, intravenous administration of cyclooxygenase-2 inhibitor cc-96191 showed improvement in quality of life parameters and an increase in quality of life over the entire trial period for patients with leukemia. For patients with myeloid, acute leukemia, and at the end of consolidation therapy, patients who were randomized to treatment in addition to a standard regime experienced improvement in EORTC QLQ scale at all time points. The drug was well tolerated; no safety concerns were identified during the study.

We are in the process of improving the odds of achieving remission and controlling the disease. The new studies are still in the process of being performed, and it may be a few years until everyone can be treated using modern chemotherapy protocols. However the data we are collecting will lead us to the drugs being used to treat the most important patients who will benefit the most, which will help lead the research to find the cures for this disease.

We conclude that CC-96191 is typically used in combination with other agents, particularly gemcitabine and docetaxel and has shown clinical activity against CLL as a single agent. The activity profile of CC-96191 indicates possible anti-apoptotic activities as part of its mechanism of action which needs to be investigated further.

For the treatment of children with B-cell precursor ALL, the [CC-96191] regimen is in fact more effective than a placebo. We recommend the inclusion of this treatment into clinical practice.