Can Calquence (ibrutinib) increase the risk of infection?

Can Calquence Lead to Infection?

Yes, Calquence (acalabrutinib) can lead to serious and potentially fatal infections, and this is a well-established risk that requires vigilant monitoring and, in select high-risk patients, prophylactic antimicrobial therapy. 1

Infection Risk Profile

The FDA label explicitly warns that fatal and serious infections, including opportunistic infections, have occurred in patients treated with Calquence 1. In clinical trials of 1,029 patients:

• Serious or Grade 3+ infections occurred in 19% of patients
• Respiratory tract infections were most common (11% of all patients)
• Pneumonia specifically affected 6% of patients
• Neutropenic infection occurred in 1.9% 1

Importantly, most infections occurred even without severe neutropenia, indicating that Calquence's infection risk stems from immune dysfunction beyond simple white blood cell suppression 1.

Types of Infections to Monitor

Opportunistic Infections

Calquence increases risk for 1:

• Hepatitis B virus reactivation
• Fungal pneumonia
• Pneumocystis jirovecii pneumonia (PJP)
• Epstein-Barr virus reactivation
• Cytomegalovirus
• Progressive multifocal leukoencephalopathy (PML)

Invasive Fungal Infections (IFI)

While BTK inhibitors like Calquence carry a slightly increased rate of IFI (still <3%), there is notable concern for central nervous system involvement 2. The incidence ranges from 1.3-2.8% in recent studies, with aspergillosis being most common 2.

Who Needs Prophylaxis?

Current 2024 guidelines indicate that universal antimicrobial prophylaxis is NOT routinely recommended for Calquence monotherapy 2. However, prophylaxis IS warranted when additional risk factors are present:

Mandatory Prophylaxis Situations:

• Hepatitis B: All HBsAg-positive patients require antiviral prophylaxis with entecavir or tenofovir 2
• Combination therapy with anti-CD20 antibodies (e.g., rituximab, obinutuzumab) 2
• Concurrent high-dose or prolonged corticosteroid use 2
• Recent purine analogue therapy (fludarabine) or alemtuzumab (within 3 months) 2
• Recurrent or persistent neutropenia 2
• Previous invasive fungal infection 2
• First 6 months of BTK inhibitor therapy in heavily pretreated patients 2

PJP Prophylaxis

Not routinely needed for Calquence monotherapy, as the risk is <3% 2. Reserve for patients with the additional risk factors listed above.

Antifungal Prophylaxis

Not recommended universally due to:

1. Low baseline IFI risk (1.3-2.8%) in patients without other risk factors 2
2. Significant drug-drug interactions between azole antifungals and Calquence (both use CYP3A4 pathway, leading to increased Calquence levels and toxicity) 2

Use individualized antifungal prophylaxis only in patients with multiple risk factors listed above.

Clinical Management Algorithm

Before Starting Calquence:

1. Screen for hepatitis B (HBsAg, HBcAb, HBsAb) 2
2. Vaccinate against pneumococcus, influenza, herpes zoster, and COVID-19 (preferably before treatment initiation) 2
3. Assess baseline risk factors: prior infections, concurrent medications, performance status, comorbidities

During Treatment:

1. Monitor for infection symptoms (fever, chills, respiratory symptoms) 1

2. Rapid diagnostic workup for any suspected infection:

   • Blood cultures
   • Lung CT scan for respiratory symptoms
   • Serum galactomannan and beta-D-glucan for fungal infections
   • Consider BAL fluid testing if pneumonia suspected
   • Brain MRI and lumbar puncture if CNS symptoms (critical for fungal infections) 2

3. Monitor hepatitis B (if at risk): AST and HBV-DNA every 1-6 months during treatment, then every 3-6 months after completion 2

Treatment Modifications:

• Hold Calquence 3-7 days before surgery (depending on procedure type and bleeding risk) 1
• Interrupt or reduce dose if serious infection develops 1
• Manage drug interactions carefully (e.g., with COVID-19 antivirals like nirmatrelvir/ritonavir, which significantly increase Calquence levels) 2

Real-World Data Context

Research studies show infection rates may be higher in real-world practice than clinical trials, with severe infection rates of 36-48% reported 3, 4. Risk factors consistently associated with increased infection include:

• Advanced age 5
• Poor performance status (ECOG ≥2) 4, 5
• High comorbidity burden 4
• Prior stem cell transplantation 3
• Concurrent corticosteroids or cytotoxic agents 3, 5

Critical Pitfalls to Avoid

1. Don't assume neutropenia is required for serious infection - most infections with Calquence occur without Grade 3-4 neutropenia 1
2. Don't overlook CNS involvement in fungal infections - BTK inhibitors have unusual propensity for CNS aspergillosis 2
3. Don't use azole antifungals without dose adjustment - significant drug interaction increases Calquence toxicity 2
4. Don't forget hepatitis B screening - reactivation can be fatal 2
5. Don't provide universal prophylaxis - reserve for high-risk patients to avoid unnecessary drug exposure and interactions 2

The infection risk with Calquence is real and clinically significant, but targeted surveillance and risk-stratified prophylaxis are more appropriate than universal antimicrobial coverage 2.