In late December 2020, biopharmaceutical company AbbVie announced via press release that the prescribing information for IMBRUVICA (ibrutinib) is now updated to include long-term safety and efficacy data for Waldenstrom macroglobulinemia (WM). The data, sourced from the Phase 3 iNNOVATE clinical trial, evaluated IMBRUVICA and rituximab as a potential therapeutic option for WM.
IMBRUVICA
IMBRUVICA (ibrutinib) was first approved for use in 2013, and was designed for patients with graft-versus-host disease (GvHD) and hematological malignancies. Two years later, it was approved for use in patients with WM and was later approved for use in conjunction with rituximab in 2018.
Its later approval hinged on data from the Phase 3 iNNOVATE trial. Altogether, 150 patients enrolled. During the trial, patients received 375 mg/m2 rituximab administered intravenously for 1 month. Next, they received another 1-month rituximab cycle after 3 months. Additionally, patients received either a placebo or 420mg IMBRUVICA daily until specific criteria were met. The iNNOVATE trial’s primary endpoint was progression-free survival. The secondary endpoints included hemoglobin improvement, overall response rate, time between treatments, survival rates, and adverse reactions. Some side effects observed during the trial included:
- Diarrhea
- Rashes
- Joint and muscle pain
- Easy bruising and bleeding
- Nausea
- High blood pressure
Altogether, patients using IMBRUVICA with rituximab saw a 75% less chance of death or disease progression than those just using rituximab.
What is IMBRUVICA?
IMBRUVICA is a Bruton’s tyrosine kinase (BTK) inhibitor, the first in its class to be FDA-approved for WM. In an article published in the American Journal of Managed Care, authors explain that:
the BTK protein is essential to helping B cells develop and mature into functional and specialized white blood cells; these are part of the adaptive immune response in producing antibodies, or immunoglobulins. But mutations in the BTK gene…can lead to a sizable reduction in the number of circulating B cells, along with reduced ability to fight infection…production of abnormal BTK protein, or cancer cell growth; mutated immunoglobulins essentially malfunction…by not recognizing antigens as damaging.
Thus, the article continues, BTK inhibitors work because they:
help to trigger cell death by blocking the B-cell receptor signaling that leukemias and lymphomas use to grow and survive.
IMBRUVICA is approved for use in 101 countries. Altogether, over 200,000 patients across the globe have been treated with this therapy. Additionally, IMBRUVICA received four separate Breakthrough Therapy designations within the United States.
Safety Information
IMBRUVICA should be taken by mouth, with a full glass of water, once daily. The pill should not be broken or chewed. Every day, the treatment should be taken at (or around) the same time. Do not drink grapefruit juice, or eat either grapefruit or Seville oranges, while taking IMBRUVICA. If you have frequent bleeding or liver issues, are pregnant or trying, or have heart issues, please speak to your doctor before taking this therapy. Side effects include:
- Nausea and vomiting
- Diarrhea
- Easy bruising
- Fatigue
- Muscle, joint, and bone pain
- Rashes
- Canker sores
- Muscle spasms
- Pneumonia
For more serious side effects, listed below, please contact your doctor immediately for care:
- High blood pressure
- Infections or signs of infections such as fever, chills, or mental confusion
- Anemia (low red blood cell count)
- Thrombocytopenia (low platelet count)
- Neutropenia (low white blood cell count)
- Hemorrhages
- Bloody stool and/or pink or brown-tinted urine
- Unexpected or extremely severe bruising and bleeding
- Bloody vomit
- Skin or organ cancer
- Tumor lysis syndrome
- Irregular heartbeat
- Atrial fibrillation
- Swelling of the lower extremities
- Heart and organ failure
Waldenstrom Macroglobulinemia (WM)
Overall, researchers are not sure what causes Waldenstrom macroglobulinemia (WM), a type of cancer that begins in lymphocytes (white blood cells which play a role in the immune system). However, up to 90% of patients with WM have a MYD88 gene mutation. Normally, B lymphocytes protect the body from infections and diseases. But in WM, cancerous cells over-produce an abnormal type of immunoglobulin M called macroglobulin. As the cancerous cells increase, normal blood cells are overcrowded. The blood becomes hyperviscous (abnormally thick). An estimated 1-2% of all blood cancers are WM. This cancer is more common in Caucasians and more than 2x more likely in males than females. In many cases, WM is diagnosed when patients are in their mid- to late-60s. Symptoms include:
- Fatigue
- Anemia (low red blood cell counts)
- Muscle weakness
- Shortness of breath
- Frequent infections
- Easy bruising and bleeding
- Dizziness and headaches
- Diarrhea
- Unintended weight loss
- Changes in vision, such as blurred vision or vision loss
- Difficulty concentrating
- Enlarged lymph nodes
- Abdominal swelling
