What are the adverse effects of Calquence (acalabrutinib) and the recommended monitoring and management strategies?

Side Effects of Calquence (Acalabrutinib)

Calquence causes common but manageable side effects including headache (22-51%), diarrhea (37-58%), musculoskeletal pain (21%), and infections (65%), with most being mild to moderate in severity, while serious adverse events include cytopenias (grade 3-4 neutropenia in 14-26%), bleeding (2% grade ≥3), atrial fibrillation (4-7%), and opportunistic infections (grade ≥3 in 14%). 1, 2

Most Common Side Effects

Headache

• Occurs in 22-51% of patients and is the most frequently reported adverse event 3, 1, 2
• Typically self-limited and resolves within 1-2 months of treatment initiation 1, 4
• Managed with acetaminophen plus caffeine supplements as first-line therapy 1, 4
• Patients should not discontinue acalabrutinib prematurely for headaches given their transient nature 1

Gastrointestinal Effects

• Diarrhea occurs in 37-58% of patients (grade ≥3 in only 5%) 3, 1, 4, 2
• Nausea occurs in 7-27% of patients 3, 1
• Most gastrointestinal symptoms are grade 1-2 and manageable with supportive care 5

Musculoskeletal Pain

• Arthralgia, including back and leg pain, occurs in 21% of patients 3, 1
• Most complaints are mild to moderate (grade 1-2) 1

Constitutional Symptoms

• Fatigue occurs in 10-32% of patients 3, 4, 2
• Pyrexia (fever) occurs in 12-21% of patients 3, 4

Serious Hematologic Adverse Events

Cytopenias

• Grade 3-4 neutropenia occurs in 14-26% of patients, with grade 4 neutropenia in 14% 3, 1, 2
• Grade 3-4 thrombocytopenia occurs in 7-10% of patients 3, 1, 2
• Grade 3-4 anemia occurs in 7-15% of patients 3, 1, 2
• Monitor complete blood counts regularly during treatment and interrupt, reduce dose, or discontinue as warranted 2

Cardiovascular Adverse Events

Atrial Fibrillation and Hypertension

• Atrial fibrillation occurs in 4-7% overall (grade ≥3 in 1%) 1, 4, 2
• Hypertension occurs in 3-7% overall (grade ≥3 in 2-3%) 1, 4
• Acalabrutinib is preferred over ibrutinib in patients with cardiovascular comorbidities due to significantly lower rates of atrial fibrillation and hypertension 1
• Monitor for symptoms of arrhythmia including palpitations, dizziness, syncope, and dyspnea 2
• Risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection 2

Bleeding Events

• Overall bleeding risk is 26-39% for any grade bleeding 1, 4
• Grade ≥3 bleeding occurs in only 2% of patients 1, 4
• Major hemorrhage (serious or grade 3+ bleeding or any CNS bleeding) occurs in 3.0% of patients, with fatal hemorrhage in 0.1% 2
• Patients on antiplatelet or anticoagulant therapies require careful monitoring 1, 4
• Avoid concomitant warfarin use; patients requiring anticoagulation need alternative agents 1, 4
• Consider withholding acalabrutinib 3-7 days pre- and post-surgery depending on surgery type and bleeding risk 2

Infectious Complications

Overall Infection Risk

• Overall infection rate is 65%, with grade ≥3 infections in 14% of patients 1, 4, 2
• Respiratory tract infections occur in 32-36% of patients, including pneumonia in 6-7% 1, 6, 2
• Upper respiratory tract infections occur in 24-36% of patients 3, 2

Opportunistic Infections

• Serious or opportunistic infections include hepatitis B reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy 2
• Consider prophylaxis in patients at increased risk for opportunistic infections 2
• Routine antibiotic or antifungal prophylaxis is NOT recommended unless additional risk factors are present 6

Second Primary Malignancies

• Second primary malignancies occur in 18% of patients exposed to acalabrutinib 2
• Non-melanoma skin cancer is most frequent (10%), followed by other solid tumors (9%) including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers 2
• Hematologic malignancies occur in 1% of patients 2
• Monitor patients for development of second cancers and advise sun protection 2

Hepatotoxicity

• Drug-induced liver injury (DILI) has occurred with BTK inhibitors including acalabrutinib, with severe, life-threatening, and potentially fatal cases reported 2
• Evaluate bilirubin and transaminases at baseline and throughout treatment 2
• If DILI is suspected, withhold acalabrutinib; upon confirmation, discontinue permanently 2

Critical Drug Interactions and Management Pitfalls

Drug Interactions

• Ciprofloxacin significantly increases plasma concentrations of acalabrutinib and should be avoided 6
• Azole antifungals have significant interactions through CYP3A4 inhibition, leading to increased acalabrutinib levels and potential toxicities 6

Adherence and Dose Modifications

• When doses are missed due to manageable side effects, reeducate patients about adherence rather than discontinuing therapy 1, 7
• Grade 1-2 adverse events can be managed with over-the-counter medications without dose modification 7
• For grade 3-4 toxicities, interrupt treatment until recovery to grade 1 or baseline, then resume at the same or reduced dose 2

Monitoring Strategy

Implement the following monitoring protocol:

• Complete blood counts regularly throughout treatment 2
• Liver function tests at baseline and throughout treatment 2
• Cardiovascular monitoring for arrhythmias and hypertension 1, 2
• Signs and symptoms of infection with prompt treatment 2
• Bleeding events, especially in patients on antithrombotic agents 2
• Skin examinations for second primary malignancies 2