Does Calquence (acalabrutinib) cause immunocompromise?

From the Guidelines

Calquence (acalabrutinib) can make you immunocompromised, particularly by increasing the risk of secondary hypogammaglobulinemia, which may lead to severe or repeated infections. This medication is a Bruton's tyrosine kinase (BTK) inhibitor used to treat certain blood cancers like chronic lymphocytic leukemia and mantle cell lymphoma. Calquence works by blocking signals that cancer cells need to grow and survive, but it also affects normal immune cell function, particularly B cells which are important for fighting infections. As a result, patients taking Calquence typically experience some degree of immunosuppression, making them more susceptible to infections, as reported in a study published in Blood Reviews 1.

Key Considerations

• The risk of hypogammaglobulinemia during treatment with BTK inhibitors like Calquence is a significant concern, and monitoring of serum immunoglobulin levels is recommended 1.
• Immunoglobulin replacement therapy (IgRT) may be considered in patients with hypogammaglobulinemia and severe or repeated infections, with a target trough of 600-800 mg/dL 1.
• Subcutaneous immunoglobulin therapy (SCIg) has been shown to be effective in increasing IgG levels and reducing infectious episodes in patients with hypogammaglobulinemia, including those receiving BTK inhibitors like Calquence 1.

Patient Management

• Patients taking Calquence should take precautions against infection, including practicing good hygiene, avoiding people with active infections, and promptly reporting fever or other signs of infection to their healthcare provider.
• Regular monitoring of blood counts is essential while on this medication to track immune system function.
• Healthcare providers should consider the risk of secondary hypogammaglobulinemia and the potential benefits of IgRT in patients receiving Calquence, particularly those with a history of recurrent or severe infections.

From the FDA Drug Label

1. 1 Serious and Opportunistic Infections Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%) Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections.

Yes, Calquence can make you immunocompromised, as it increases the risk of serious and opportunistic infections, including fungal, viral, and bacterial infections.

• Key points:
  • Serious or Grade 3 or higher infections occurred in 19% of patients exposed to CALQUENCE.
  • Opportunistic infections, such as hepatitis B virus reactivation and Pneumocystis jirovecii pneumonia, have been reported.
  • Prophylaxis should be considered in patients at increased risk for opportunistic infections 2.

From the Research

Immunocompromised State and Calquence

• Calquence, also known as acalabrutinib, is a selective Bruton tyrosine kinase inhibitor used in the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) 3, 4.
• The mechanism of action of acalabrutinib involves inhibiting the activity of Bruton tyrosine kinase, which prevents the activation of the B-cell receptor signaling pathway, leading to the prevention of B-cell activation and BTK-mediated activation of downstream survival pathways 4.
• As acalabrutinib targets B cells, it may affect the immune system, potentially leading to an immunocompromised state.
• However, the provided studies do not directly address whether Calquence makes patients immunocompromised 3, 4, 5, 6, 7.
• The studies focus on the efficacy and safety of acalabrutinib in patients with CLL and MCL, with reported adverse events and toxicity profiles, but do not explicitly discuss the immunocompromised state as an outcome 3, 4, 5, 6, 7.

Adverse Events and Toxicity Profile

• The studies report that acalabrutinib has a tolerable safety profile, with most adverse events being grade 1/2 severity, and a low rate of discontinuation due to adverse events 3, 4, 6, 7.
• Common adverse events include headache, diarrhea, and fatigue, with grade 3 or greater adverse events reported in a significant proportion of patients 6.
• The toxicity profile of acalabrutinib is compared to other BTK inhibitors, such as ibrutinib, with acalabrutinib demonstrating a superior safety profile in some studies 7.

Efficacy and Clinical Outcomes

• The studies demonstrate the efficacy of acalabrutinib in improving progression-free survival in patients with CLL and MCL, with significant benefits observed in clinical trials 3, 4, 6.
• Overall response rates and complete response rates are also reported, with acalabrutinib showing promising results in patients with previously untreated or relapsed/refractory CLL and MCL 6.