Across phase 3 CLL trials, acalabrutinib-based regimens significantly improved progression-free survival versus standard chemoimmunotherapy, with no reported clinically relevant differences in efficacy between men and women.

For CLL, the recommended dose is 100 mg acalabrutinib orally twice daily, as monotherapy or in combination (with obinutuzumab and/or venetoclax), given approximately every 12 hours and continued until disease progression, unacceptable toxicity, or completion of 14 cycles in the fixed-duration venetoclax regimen.

No sex-specific dose adjustments are recommended; dose interruptions and resumption at 100 mg twice daily or reduced to once daily are guided by the severity and recurrence of haematologic or non-haematologic toxicity, regardless of sex.

No sex-specific differences in the type or frequency of adverse reactions were reported in CLL studies.

In clinical studies in haematologic malignancies, very common adverse drug reactions (≥20%) with Calquence monotherapy included infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea and rash. With Calquence in combination with obinutuzumab, very common ADRs included infection, musculoskeletal pain, diarrhoea, headache, leukopenia, neutropenia, cough, fatigue, arthralgia, nausea, dizziness and constipation. In combinations with venetoclax (with or without obinutuzumab), very common ADRs included infections, neutropenia, headache, bruising, diarrhoea, nausea and musculoskeletal pain. In combination with bendamustine and rituximab, very common ADRs included neutropenia, nausea, rash, diarrhoea, musculoskeletal pain, headache, fatigue, vomiting, constipation, anaemia and thrombocytopenia. From pooled monotherapy data, common serious or grade ≥3 ADRs included infections, leukopenia, neutropenia, anaemia, second primary malignancies and thrombocytopenia. Very common specific events in tables included upper respiratory tract infection, pneumonia, neutropenia, anaemia, thrombocytopenia, bruising, haemorrhage/haematoma (including gastrointestinal and intracranial haemorrhage), hypertension, diarrhoea, nausea, constipation, abdominal pain, vomiting, rash, musculoskeletal pain, arthralgia and fatigue. Important serious reactions highlighted in warnings included major haemorrhagic events (including central nervous system and gastrointestinal haemorrhage, some fatal), serious bacterial, viral and fungal infections (including hepatitis B reactivation, herpes zoster, aspergillosis and PML), atrial fibrillation/flutter, tumour lysis syndrome, interstitial lung disease/pneumonitis and second primary malignancies (notably skin cancers). Discontinuations due to adverse reactions occurred in 14.6% of patients on monotherapy, most often because of pneumonia, thrombocytopenia and diarrhoea, and in 7.6–13.7% of patients in venetoclax-based CLL combinations and 10.8% in the obinutuzumab CLL combination. In the Calquence+bendamustine+rituximab MCL regimen, discontinuation of Calquence due to adverse reactions was reported in 42.8% of patients (most often COVID‑19, COVID‑19 pneumonia, neutropenia and pneumonia). Dose reductions due to adverse reactions occurred in 5.9% of monotherapy patients and 5.8–10.1% of patients in combination regimens, commonly due to neutropenia, diarrhoea, vomiting, nausea, hepatitis B reactivation or sepsis.

Use of acalabrutinib during pregnancy is not recommended unless clearly needed because animal data show reproductive toxicity, and women of childbearing potential should avoid becoming pregnant during treatment; breastfeeding should be avoided during therapy and for 2 days after the last dose due to potential risk to the breast-fed child.

Non-clinical studies in male and female rats showed no adverse effects of acalabrutinib on fertility parameters, and population pharmacokinetic analyses found no clinically meaningful impact of sex on acalabrutinib or ACP-5862 exposure.