Acalabrutinib represents a significant advancement in treating Mantle Cell Lymphoma (MCL), a challenging type of blood cancer. This medication offers a targeted approach, precisely inhibiting cancer cell growth compared to traditional therapies. Understanding its mechanism and place in the treatment landscape is important for patients and families seeking current information. It aims to improve outcomes and manage MCL symptoms.
Understanding Mantle Cell Lymphoma
Mantle Cell Lymphoma (MCL) is a rare form of non-Hodgkin lymphoma originating in the lymphatic system. It develops from malignant B-lymphocytes, specifically within the “mantle zone” of lymph nodes. MCL accounts for 5% to 7% of all non-Hodgkin lymphomas in the United States, with an annual incidence of about one case per 200,000 people. It is more commonly diagnosed in men, usually between 60 and 70 years of age.
The disease often presents with widespread involvement at diagnosis, affecting multiple lymph nodes, the spleen, and potentially the bone marrow, liver, and gastrointestinal tract. A hallmark of MCL is the t(11;14) translocation, a genetic change leading to overexpression of cyclin D1. This causes abnormal B cells to multiply uncontrollably, forming tumors. While MCL can be aggressive, some variants follow a more indolent course.
Acalabrutinib: A Targeted Therapy
Acalabrutinib, known as Calquence, is a targeted therapy specifically designed to treat MCL. It belongs to a class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors. The U.S. Food and Drug Administration (FDA) has approved acalabrutinib for adult patients with previously untreated MCL who are not eligible for autologous hematopoietic stem cell transplantation. It also holds approval as a single agent for adults with MCL who have received at least one prior therapy, with full approval granted in January 2025.
This medication is “targeted” because it acts on specific molecules involved in cancer cell growth, unlike traditional chemotherapy which affects rapidly dividing cells throughout the body. Acalabrutinib is a second-generation BTK inhibitor, developed to be more selective than earlier inhibitors like ibrutinib. This increased selectivity aims to reduce interactions with other proteins, potentially leading to fewer off-target side effects.
How Acalabrutinib Works
Acalabrutinib targets and inhibits Bruton’s tyrosine kinase (BTK), a protein inside B-cells. BTK plays a significant role in the B-cell receptor (BCR) signaling pathway, responsible for B-cell growth and survival. In MCL, this pathway becomes overactive, leading to uncontrolled B-cell multiplication.
Acalabrutinib forms an irreversible bond with the BTK enzyme, blocking its activity. By inhibiting BTK, it disrupts the overactive BCR signaling pathway in MCL cells. This disruption triggers programmed cell death (apoptosis) in the B-cells and prevents their growth and spread.
Treatment Experience and Expectations
Patients prescribed acalabrutinib for MCL take it orally, typically as a 100 mg tablet twice daily. This medication continues until disease progression or unacceptable side effects occur. For previously untreated MCL patients not eligible for autologous hematopoietic stem cell transplantation, acalabrutinib can be prescribed in combination with bendamustine and rituximab. In this combination, acalabrutinib is started with bendamustine and rituximab, which are administered intravenously for six 28-day cycles.
Clinical trials show promising outcomes. In a study of patients with relapsed or refractory MCL, the overall response rate (ORR), meaning a partial or complete remission, was 81.5%, with a complete response rate of 47.6%. The median duration of response was 28.6 months, and the median progression-free survival (PFS) was 22.0 months. For previously untreated MCL, the ECHO Phase III trial demonstrated that acalabrutinib combined with bendamustine and rituximab significantly prolonged PFS. The median PFS in the acalabrutinib combination group was 66.4 months, compared to 49.6 months for those receiving chemoimmunotherapy alone, representing a 27% reduction in the risk of disease progression or death.
Managing Potential Side Effects
While acalabrutinib offers significant benefits, patients may experience side effects. Common side effects reported in clinical studies include headache (38%), bleeding (31%), diarrhea (31%), fatigue (27%), and muscle pain (21%). Other reported effects include cough (19%), nausea (18%), and fever (15%). Less common but serious side effects can include infections, bleeding problems, decreased blood cell counts, and heart rhythm problems.
Many side effects can be managed with appropriate care.
- Headaches may be relieved with over-the-counter medications or caffeine.
- Diarrhea can be managed by drinking clear liquids and eating smaller, more frequent meals.
- Muscle and bone pain may be eased with stretching or over-the-counter pain relievers.
- Bruising can be reduced by icing the area.
- Nausea may be helped by bland foods, avoiding skipped meals, or consuming food at room temperature.
It is important to communicate any side effects, especially if severe, persistent, or worsening, with a healthcare provider for personalized guidance.