Two Drugs Show Efficacy against Common Form of Leukemia


 Acalabrutinib (ACP-196) targets BTK, a key switch in a signaling pathway required for the growth and survival of chronic lymphocytic leukemia cells. Credit: Adrian Wiestner, M.D., NHLBI

Acalabrutinib (ACP-196) targets BTK, a key switch in a signaling pathway required for the growth and survival of chronic lymphocytic leukemia cells. Credit: Adrian Wiestner, M.D., NHLBI

Reports from two early-stage trials of new oral drugs provide hope for patients with high-risk chronic lymphocytic leukemia (CLL) that has returned after prior treatment.

Results from both trials were presented last month at the annual meeting of the American Society of Hematology (ASH) and published in the New England Journal of Medicine (NEJM).

Some patients with CLL, the most common type of leukemia in the United States, do well even without treatment, whereas others need chemotherapy to manage their disease.

Chemotherapy can keep the disease in check for years without symptoms or need for further treatment, but virtually all patients relapse. Ultimately, for most patients, there is no curative therapy.

Relapsed CLL becomes harder to treat as patients’ tumors acquire a number of genetic abnormalities. The loss of part of chromosome 17, referred to as deletion 17p, is common in CLL and strongly associated with resistance to chemotherapy. Patients whose tumors develop deletion 17p are considered to be at high risk of disease progression and have an expected survival of only a few years.

A More Selective BTK Inhibitor

Findings from a clinical trial led by John C. Byrd, M.D., of the Ohio State University, showed that the drug acalabrutinib was both safe and effective. Of the 61 patients with relapsed CLL enrolled in the trial, 95 percent had a complete or partial tumor response, including patients with deletion 17p. After a median of 14 months, one patient died of pneumonia and one patient developed treatment-resistant CLL.

Acalabrutinib blocks Bruton tyrosine kinase (BTK), a key switch in the signaling pathway required for the growth and survival of CLL cells. Acalabrutinib follows in the steps of ibrutinib (Imbruvica®), the first BTK inhibitor to be developed, which was approved by the Food and Drug Administration (FDA) in 2014 for some patients with CLL. While ibrutinib inhibits BTK and several other kinases, acalabrutinib is more selective, targeting BTK only.

“It’s very encouraging that there is a second BTK inhibitor that shows a very high rate of response in patients with CLL, even in those otherwise considered at high risk of treatment failure, and also has very good tolerability,” said Adrian Wiestner, M.D., an investigator at the National Heart, Lung, and Blood Institute, who studies CLL but was not involved in the trial.

Taken together with the larger clinical experience with ibrutinib, the findings validate that targeting BTK can improve the outlook for patients with CLL, providing an effective option compared with existing therapies, said Dr. Wiestner.

“The benefit of having different drugs that can hit the same target in a tumor cell is that, if one drug leads to intolerable side effects, the other can be used,” he continued. “Conceivably, in some situations, one of the drugs may be safer or more efficacious than the other. Thus, having a choice can make a very good situation even better.”

Strong Responses with Venetoclax

Promising findings from a study testing another new drug in patients with high-risk CLL were also published in NEJM and presented at ASH. Andrew W. Roberts, Ph.D., of the University of Melbourne in Australia, led a 116-patient phase II trial of the investigational drug venetoclax, in which nearly 80 percent of patients responded to the drug and, in about 85 percent of those patients, the responses lasted for a year or more. Common side effects included mild diarrhea and upper respiratory infections.

Venetoclax works in a different way than ibrutinib and acalabrutinib. The drug targets the BCL2 protein, which, among other things, regulates the process of cell death, or apoptosis. CLL cells tend to produce excessive amounts of BCL2, preventing apoptosis. By blocking BCL2 activity, venetoclax reactivates the normal process of apoptosis, leading to the death of CLL cells.

“The big step forward is that we now have different drugs that kill tumor cells in unique ways,” Dr. Wiestner said. “This offers the potential for combinations that can really deliver a two-pronged attack on the tumor cells and hopefully can be the building blocks for treatments that lead not only to long-term survival, but also to long-term treatment-free periods for patients with CLL.”

Source: National Cancer Institute



About LFCT

This is a blog about CHILDHOOD CANCER and CHILDHOOD CANCER AWARENESS Little Fighters Cancer Trust is a non-profit organisation that offers support and aid to Children with Cancer and their families. When a child is diagnosed with cancer it affects the whole family. One of the parents, usually the mother, must give up their job to care for the child and this creates financial problems for the family. In South Africa especially the majority of these families are not well-to-do; many of them are rural. A diagnosis of cancer can wipe out any family’s finances, let alone a poor family. The costs of special medications, special diets, hospital stays, transport to and from the hospital or clinic and accommodation and food costs for the mother who spends most of the time at her child’s bedside are astronomical. These are the people and problems that fall through the cracks, and these are the people that Little Fighters Cancer Trust has pledged to help in any way possible. LFCT takes a holistic approach to assisting the Children with Cancer and their Families, with the main aim to be the preservation of individual dignity and pride. Little Fighters Cancer Trust also focuses on promotion and advocacy of National Childhood Cancer Awareness in an effort to increase awareness of Early Warning Signs of Childhood Cancer. This would result in earlier diagnosis, giving the Child with Cancer more of a chance at Treatment and Survival. See "About" for more Background info

Posted on 22 January, 2016, in Blog, Research and tagged , , , , . Bookmark the permalink. Leave a comment.

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