Can Acalabrutinib (Bruton's tyrosine kinase inhibitor) cause back and leg pain, as well as headaches?

Acalabrutinib Side Effects: Back/Leg Pain and Headaches

Yes, acalabrutinib commonly causes headaches (occurring in 22-51% of patients) and arthralgia/musculoskeletal pain including back and leg pain (occurring in 21% of patients), though these are typically mild to moderate in severity and manageable with conservative measures. 1, 2

Headaches with Acalabrutinib

Headaches are one of the most characteristic side effects of acalabrutinib, but they are generally self-limited and resolve within 1-2 months of treatment initiation. 1, 2

Incidence and Severity

• Headaches occur in 22-51% of patients receiving acalabrutinib 1, 3, 4
• The vast majority are grade 1-2 in severity, with only 1% experiencing grade ≥3 headache 5
• In the ASCEND trial, headache was reported in 22% of patients 1
• Among ibrutinib-intolerant patients switched to acalabrutinib, headache occurred in 39-42% 1, 4

Management Strategy

• First-line management: acetaminophen (paracetamol) plus caffeine supplements 1, 2
• Over-the-counter analgesics are typically sufficient for grade 1-2 headaches 3
• Headaches typically resolve spontaneously after 1-2 months of continued treatment 1, 2
• Patient education about the self-limited nature of this side effect improves adherence 3
• No patients discontinued acalabrutinib due to headache in major clinical trials 3

Back and Leg Pain (Arthralgia/Musculoskeletal Pain)

Arthralgia, which includes back and leg pain, occurs in approximately 21% of patients treated with acalabrutinib. 1

Clinical Characteristics

• Arthralgia was reported in 21% of patients in the ibrutinib-intolerant cohort 1
• Most musculoskeletal complaints are mild to moderate (grade 1-2) 1
• These symptoms are generally manageable with standard analgesics 3

Important Context

• Acalabrutinib has a more favorable overall side effect profile compared to ibrutinib, particularly regarding cardiovascular toxicity 1, 2
• The more selective BTK inhibition of acalabrutinib may contribute to its different adverse event profile 4, 6

Other Common Side Effects to Monitor

Gastrointestinal

• Diarrhea occurs in 52-58% of patients (grade ≥3 in 5%) 1, 2, 4, 6
• Nausea occurs in 7-27% of patients 1

Hematologic

• Neutropenia (grade ≥3) occurs in 14-19% of patients 1, 7, 6
• Thrombocytopenia (grade ≥3) occurs in 7-9% of patients 1, 7
• Anemia (grade ≥3) occurs in 7-15% of patients 1, 7

Cardiovascular (Lower Risk than Ibrutinib)

• Atrial fibrillation occurs in 4-7% overall (grade ≥3 in 1%) 1, 2, 7
• Hypertension occurs in 3-7% overall (grade ≥3 in 2-3%) 1, 2, 6
• Acalabrutinib is preferred over ibrutinib in patients with cardiovascular comorbidities due to lower rates of atrial fibrillation and hypertension 1

Bleeding Events

• Overall bleeding risk is 26-39% for any grade, but only 2% for grade ≥3 bleeding 1, 2
• Avoid concomitant warfarin use; monitor patients on antiplatelet or anticoagulant therapies 1, 2

Infections

• Overall infection rate is 65%, with grade ≥3 infections in 14% of patients 1, 2
• Pneumonia (grade ≥3) occurs in 10-11% of patients 7, 6

Key Clinical Pitfalls

• Do not discontinue acalabrutinib prematurely for headaches—they typically resolve within 1-2 months with conservative management 1, 2, 3
• Reeducate patients about adherence when doses are missed due to manageable side effects 3
• Monitor for cardiovascular events (atrial fibrillation, hypertension) even though rates are lower than with ibrutinib 1
• Avoid concomitant warfarin—patients requiring anticoagulation need alternative agents 1, 2
• Watch for drug interactions with CYP3A4 inhibitors (e.g., azole antifungals) that can increase acalabrutinib levels 8