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New Drug Can Improve Survival in Blood Cancer

by Pooja Shete on Dec 8 2020 12:34 PM

New Drug Can Improve Survival in Blood Cancer
Venetoclax cause the self-destruction of the cancer cells. The combination of venetoclax, fludarabine, and busulfan shows promising clinical activity.
Myeloid blood cancer is the cancer of blood and bone marrow with an excess of immature white blood cells (WBCs). Early studies show that when oral drug venetoclax was added to the standard therapy of some high-risk myeloid blood cancers, promising results were seen. The study was conducted by scientists at the Dana-Farber Cancer Institute.

Venetoclax causes cancer cells to self-destruct by targeting the cancer’s survival proteins which makes them more vulnerable to treatments. The drug was approved in 2016 for treating chronic lymphocytic leukemia.

It is the first drug in the class of drugs called BCL-2 (B cell Lymphoma-2) inhibitors. BCL-2 is a regulatory protein that prevents cell death. Venetoclax selectively blocks BCL-2 thus promoting cell death.

The study was presented at the 62nd American Society of Hematology (ASH) Annual Meeting. Two studies were conducted to observe the safety and efficacy of combining venetoclax with the standard treatments for myeloid blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in high-risk patients.

In the first study, venetoclax was added to the standard chemotherapy given to patients with AML or MDS before giving intensity conditioning stem cell transplantation. Patients with co-morbid conditions and older patients are usually given the reduced intensity conditioning transplants as it is less toxic. To prevent the rejection of the donor stem cells, reduced intensity conditioning chemotherapy is given which depletes the immune system.

However, this therapy is associated with a high risk of disease recurrence particularly, in patients with myeloid blood cancers. Before the patient receives a transplant to restore the blood-forming and immune systems, the investigators added venetoclax to the chemotherapy that kills AML or MDS cells.

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Pre-transplant chemotherapy consists of drugs like fludarabine, and busulfan. The investigators hoped that by adding venetoclax, the therapy would be more effective, and the chances of relapse will be less.

To test the safety and efficacy, this combination was given to 22 patients in the age group 25 to 71 who had AML, MDS, or MDS/MPN. 35 percent of patients had intermediate-risk disease and 65 percent had adverse disease risk.

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All 22 patients had a successful transplant, and no serious additional side effects were observed with the addition of venetoclax. No further increase in graft-versus-host disease (GVHD) rates was seen with addition of venetoclax.

During analysis, out of 22 patients seven patients relapsed, and five of the patients died. The overall results of the study were encouraging for high risk patient population.

No increase in toxicity was seen with the addition of venetoclax. Garcia said, “The combination of venetoclax, fludarabine, and busulfan demonstrates promising clinical activity supporting further evaluation for high risk disease features.”

In the second study, venetoclax was combined with the drug azacitidine to treat patients with high-risk MDS who require treatment but do not immediately undergo transplantation at the start of the study. Azacitidine is a drug that slows the growth of cancer cells by increases the expression of tumor-suppressor genes. The drug is a hypomethylating agent.

Azacitidine, when used alone, has a lower response rate in MDS, and the overall survival is around 15 months.

According to laboratory studies, venetoclax and azacitidine show increased effects when taken together. FDA has recently approved this combination for the treatment of untreated AML in patients who are not eligible for intensive chemotherapy.

The safety and efficacy of this combination was tested in 57 patients with high-risk MDS who had not previously been treated. The age group of the patients was between 26 to 85 years.

An overall response rate of 77 percent was seen, with a complete remission in 42 percent and complete marrow response rate of 42 percent.

Fatigue and poor quality of life due to the underlying disease are commonly reported in MDS patients. Patient-reported outcome of the population during the treatment was also evaluated. The researchers confirmed tolerability of therapy as the physical functioning was maintained through 48 weeks of treatment.

In addition, there was an improvement in fatigue and shortness of breath by the beginning of cycle 5, and it was maintained through week 48.

The most common side effects were neutropenia, nausea, and constipation. The most common serious side effect was neutropenia with fever. Treatment with antibiotics was needed to reduce the complications.

Garcia stated that the combination of venetoclax and azacitidine “demonstrates promising efficacy, including response durability, and an acceptable safety profile for patients with high-risk MDS.”

A phase 3 clinical trial (VERONA) was launched to compare azacitidine plus venetoclax to azacitidine plus placebo for the treatment of higher risk MDS based on these data.

Source-Medindia


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