Ibrutinib, Brentuximab, Blinatumomab and Idelalisib

Ibrutinib, Brentuximab, Blinatumomab and Idelalisib

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The American Society of Hematology (ASH) is the world’s largest professional society concerned with the causes and treatments of blood disorders. Every year, the best and the brightest from around the world come to attend ASH.

This year, there was a session about new FDA-approved therapies for hematologic conditions. It was held because clinicians wanted more information about some of the recent FDA approvals.

Speakers reviewed a range of information about new drugs, including ibrutinib (Imbruvica), and idelalisib (Zydelig).

For many, the December meeting of ASH serves as a showcase for all the progress that has been made in the preceding year in hematology and oncology. Here are just a few of the items people were talking about.

Ibrutinib (Imbruvica)

Different proteins or complexes, such as enzymes, play a role in cell signaling—the process by which cells "listen" and respond to chemical signals. Bruton’s Tyrosine Kinase (BTK), an enzyme that plays an important role in B-cell development, is an example of such an enzyme that regulates cell signaling. Ibrutinib is a small molecule that blocks the enzyme BTK.

By blocking this enzyme, ibrutinib interferes with a signaling pathway that certain cancer cells rely on. Based on successes thus far, the FDA has designated ibrutinib as a breakthrough therapy, with a role in treating the following malignancies:

  • Chronic lymphocytic leukemia (CLL) patients who received at least one prior treatment
  • Chronic lymphocytic leukemia (CLL) patients with 17p deletion
  • Mantle cell lymphoma (MCL) patients who received at least one prior treatment

Ibrutinib is a pill that is taken once a day and is fairly well tolerated. Use of the agent is also being investigated in the treatment of other cancers, both alone and in combination with various therapies.

Idelalisib (Zydelig)

Idelalisib is FDA-approved for people with relapsed chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin lymphoma (FL), and relapsed small lymphocytic lymphoma (SLL, another type of non-Hodgkin lymphoma).

Approval was based on the findings of a trial in 220 patients with relapsed CLL, where conventional chemotherapy was not planned. The regimen was either idelalisib + rituximab or placebo + rituximab. The trial showed an 82% reduction in the risk of cancer progression with idelalisib, so they stopped it early, letting the placebo + rituximab patients know all about idelalisib and offering them the new drug. All of the patients in the trial’s rituximab + placebo group then began receiving idelalisib.

Brentuximab vedotin (Adcetris)

This agent is an injection for intravenous infusion. Brentuximab vedotin has an interesting mechanism of action. It is an engineered antibody--it's combined with an agent that helps kill cancer cells once they reach their target.

It is targeted to a protein called CD30, which is present in classical Hodgkin lymphoma (HL) and in systemic anaplastic large cell lymphoma (sALCL).

The study discussed at ASH was the first in lymphoma to show that the addition of a maintenance drug after transplant can markedly improve patient outcomes. In the AETHERA trial, about 63% of high-risk lymphoma patients who were treated with the drug achieved a 24-month progression-free survival compared with 51% of patients who received placebo.

Blinatumomab (Blincyto)

This drug is the first of the BITE medications (Bi-specific T Cell Engager) to be approved. It has shown significant activity in B-cell acute lymphocytic leukemia (ALL) patients with minimal residual disease after induction therapy, according to researchers at ASH. Blinatumomab cleared the residual cancer cells from 78% of 112 treated patients.

According to the National Cancer Institute, blinatumomab is an engineered antibody with potential to both stimulate the immune system and go after the cancer with antineoplastic activities.

The FDA approved blinatumomab to treat patients with Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.

Watch Niccola Gokbuget, MD, explain how blinatumomab works.

CARs Leading to ALL Remission

Long-term data from a trial using chimeric antigen receptor (CAR) T cells showed these reprogrammed cells stick around for some time, doing their job, leading to pretty lengthy remissions. Many in the scientific community are optimistic about this particular kind of therapy for a variety of cancers that are otherwise hard to take on.

Note on Side Effects

Of note, all of these agents have side effects, some of which may be serious, and some of which may be as yet unknown. As with all medications, the decision to treat is influenced by what is known about the established risks and benefits of treatment and individual patient factors.

Sources

National Cancer Institute. Blinatumomab patient information. http://www.cancer.gov/drugdictionary?cdrid=487684. Accessed December 2014.

MedPageToday. http://www.medpagetoday.com/MeetingCoverage/ASHHematology/48998. Accessed December 2014.

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