Acalabrutinib — Drug Monograph

Brand names: Calquence

Drug class: BTK Inhibitor

Mechanism of Action

Second-generation, highly selective, covalent irreversible BTK inhibitor. Like ibrutinib, acalabrutinib forms a covalent bond with Cys481 in the BTK active site, blocking B-cell receptor (BCR) signaling, B-cell proliferation, and survival. Unlike ibrutinib, acalabrutinib has minimal off-target inhibition of EGFR, ITK, TEC, and TXK kinases — this improved selectivity translates to lower rates of atrial fibrillation, major bleeding, rash, and diarrhea.

FDA Indications

• Chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) — first-line and relapsed/refractory
• Mantle cell lymphoma (MCL) — relapsed/refractory (after ≥1 prior therapy)

Common Side Effects

• Headache (often transient, first weeks of therapy)
• Diarrhea
• Fatigue
• Bruising/contusion
• Musculoskeletal pain
• Nausea
• Upper respiratory tract infection
• Rash

Clinical Pearl

ELEVATE-RR trial (head-to-head acalabrutinib vs. ibrutinib in CLL) demonstrated non-inferior PFS with significantly lower rates of atrial fibrillation (9.4% vs. 16.0%) and hypertension. Headache is a class-specific adverse effect of acalabrutinib — typically transient and managed with caffeine (coffee or caffeine tablets) taken with the drug. Acalabrutinib is preferred over ibrutinib in patients with cardiac risk factors or those requiring anticoagulation.

Related Therapies & Mechanisms

• Pirtobrutinib (Jaypirca) — BTK Inhibitor · Lymphoma
• Zanubrutinib (Brukinsa) — BTK Inhibitor · Lymphoma
• Bendamustine (Treanda) — Lymphoma
• Brexucabtagene autoleucel (Tecartus) — Lymphoma