Pirtobrutinib (Jaypirca) Shows Promise in Trial

  • Jaypirca is a novel BTK inhibitor that showed promising results in the BRUIN clinical trial.
  • Patients receiving Jaypirca had a 50% ORR, with 13% achieving a CR. On average, the DOR was 8.3 months.
  • In the BRUIN trial, the most reported side effects were fatigue, pain in the muscles, diarrhea, swelling of the arms and legs, shortness of breath, pneumonia, and easy bruising.

Written by Dr. Muneeb Niazi

Mantle Cell Lymphomas (MCL) are rare blood cancers that affect the white blood cells (WBCs), one of the main cell types within the blood. These cancers are as aggressive as they are rare.

Treating them can often prove to be an uphill battle. They often reoccur after initially responding to treatments (termed relapsed) or stop responding to treatment mid-way through (termed refractory). Such cases of MCL may now be treated with pirtobrutinib (tradename: Jaypirca), which was recently approved by the Food and Drug Administration (FDA).

Jaypirca belongs to a class of medications called Bruton’s tyrosine kinase (BTK) inhibitors, which block a protein critical to the growth of cancer cells.

Traditional Treatments For Mantle Cell Lymphoma

Treatments for MCL typically consist of some combination of the following:

  • High-Dose Chemotherapy: These are toxic medications that can eliminate fast-growing cells. However, since they target all cells indiscriminately, they cause significant side effects, including unrelenting nausea, vomiting, diarrhea, and constipation.
  • Targeted therapy: These therapies exploit unique features of cancer cells and use drugs that target these features. BTK inhibitors, such as ibrutinib and duvelisib, are drugs that block the tyrosine kinase enzyme, which plays an instrumental role in the development of lymphomas.
  • Autologous Stem Cell transplant (ASCT): This procedure harvests patients’ healthy blood stem cells before obliterating their diseased cells with chemotherapy. The harvested cells are then introduced back into patients’ bodies.
  • Immunotherapy: This treatment uses a patient’s own immune system to fight the cancers within their bodies.
  • Monoclonal Antibodies: These are laboratory-generated proteins engineered to attach to specific targets on cancer cells. This process can mark these cancer cells for destruction by the body’s own immune system. They can also prevent molecules that enhance cancer growth from attaching to the cancer cells.

RELATED: A Deep Look Into the Powerful Drugs for Chronic Myeloid Leukemia: Tyrosine Kinase Inhibitors (TKIs)

A New Treatment for Difficult-to-Treat Cases: Pirtobrutinib (Jaypirca)

Jaypirca is a novel BTK inhibitor that showed promising results in the BRUIN clinical trial. The trial enrolled 120 patients with MCL who had previously been treated with other therapies, including other BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib. Most of the patients had failed at least two prior lines of therapy. These patients received oral Jayprica until their disease either progressed or they developed intolerable side effects.

The investigators measured the objective response rate (ORR). A complete response (CR) signals the disappearance of any detectable cancer within the body. A partial response (PR) indicates a decrease in the amount of but not complete disappearance of cancer. They also measured the duration of response (DOR), which is the time from the start of therapy to disease progression or death. Patients receiving Jaypirca had a 50% ORR, with 13% achieving a CR. On average, the DOR was 8.3 months.

How is Pirtobrutinib (Jaypirca) Different?

BTK inhibitors block Bruton’s tyrosine kinase (BTK), which are protein enzymes expressed on the surface of certain lymphocytes. It plays a crucial role in the development and survival of normal WBCs. It, additionally, promotes cancer cell growth in MCL. BTK inhibitors bind to the BTK proteins, which in turn prevents them from supporting cancer cell growth.

The older generation of BTK inhibitors, such as ibrutinib, would irreversibly bind to the “active site” of the BTK enzyme (termed covalent binding). Although they are extremely effective, MCL cells can often develop resistance to these drugs, which renders them ineffective. They additionally carry side effects that often lead to their discontinuation. Newer BTK inhibitors, like Jaypirca, on the other hand, reversibly bind to the enzyme at a site other than the active site. They can therefore potentially overcome the CML cell’s resistance to the first generation of the drugs. They may also carry fewer side effects.

Side-effects

Like other cancer treatments, Jaypirca is not without its side effects. Some of the more common side effects include:

  • Tiredness
  • Swelling in arms and legs
  • Fever
  • Pain in the muscles and/or joints
  • Nausea
  • Abdominal pain
  • Diarrhea
  • Constipation
  • Shortness of breath
  • Cough
  • Easy bruising
  • Tingling in the hands and feet
  • Dizziness
  • Rash

It is less common for the treatment to cause more serious side effects, however, these are possible as well. Potential serious side effects include:

  • Changes in vision
  • Memory changes
  • Urinary tract infections
  • Increased blood pressure
  • Irregular and unstable heartbeat
  • Second cancers
  • Major bleeding events (hemorrhages)
  • Harm to unborn children of pregnant patients
  • Laboratory abnormalities
    • Decreased hemoglobin
    • Decreased WBCs within the blood
    • Increased creatinine
    • Other laboratory abnormalities are also possible

In the BRUIN trial, the most reported side effects were fatigue, pain in the muscles, diarrhea, swelling of the arms and legs, shortness of breath, pneumonia, and easy bruising.