Acalabrutinib
Acalabrutinib is an oral Bruton’s tyrosine kinase inhibitor for adult patients with chronic lymphocytic leukaemia and mantle cell lymphoma.
Source:
EMA
Active Ingredients:
Indications
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
65.3%
34.7%
Clinical study participation by sex
59.9-69.7%
30.3-40.1%
Representation Gap
No sex-specific data
-5.4% to +4.4%
-4.4% to +5.4%
Sex-specific efficacy/accuracy
No sex-specific data
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.
Sex-specific posology
No sex-specific data
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.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific differences in the type or frequency of adverse reactions were reported in CLL studies.
Pregnancy / lactation
N / A
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.
Sex-specific non-clinical findings
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.
Disease prevalence by sex
Men
65.3%
Women
34.7%
Clinical study participation by sex
Men
59.9-69.7%
Women
30.3-40.1%
Representation Gap
No sex-specific data
Men
-5.4% to +4.4%
Women
-4.4% to +5.4%
Sex-specific efficacy/accuracy
No sex-specific data
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.
Sex-specific posology
No sex-specific data
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.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific differences in the type or frequency of adverse reactions were reported in CLL studies.
Pregnancy / lactation
Men
N / A
Women
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.
Sex-specific non-clinical findings
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.
General information
General Efficacy
Not reported
General Posology
Not reported
Further Dose Adjustments
Not reported
Possible Side Effects
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.
Contraindications
Not reported
Clinical Trial Type and Population
Not reported
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
75%
25%
Clinical study participation by sex
70.7-79.8%
20.2-29.3%
Representation Gap
No sex-specific data
-4.3% to +4.8%
-4.8% to +4.3%
Sex-specific efficacy/accuracy
No sex-specific data
In previously untreated and relapsed or refractory MCL, acalabrutinib-containing regimens achieved high progression-free survival and overall response rates, with no reported sex-specific differences in efficacy.
Sex-specific posology
No sex-specific data
For MCL, acalabrutinib is given at 100 mg orally twice daily, either as monotherapy in relapsed or refractory disease or in combination with bendamustine and rituximab in previously untreated patients, and is continued until disease progression or unacceptable toxicity; BR is administered for 6 cycles with optional rituximab maintenance in responders.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific differences in adverse reaction profiles were reported in MCL studies.
Pregnancy / lactation
N / A
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.
Sex-specific non-clinical findings
Non-clinical data show no adverse effects of acalabrutinib on male or female rat fertility, and pharmacokinetic analyses indicate that sex does not meaningfully affect acalabrutinib or ACP-5862 exposure.
Disease prevalence by sex
Men
75%
Women
25%
Clinical study participation by sex
Men
70.7-79.8%
Women
20.2-29.3%
Representation Gap
No sex-specific data
Men
-4.3% to +4.8%
Women
-4.8% to +4.3%
Sex-specific efficacy/accuracy
No sex-specific data
In previously untreated and relapsed or refractory MCL, acalabrutinib-containing regimens achieved high progression-free survival and overall response rates, with no reported sex-specific differences in efficacy.
Sex-specific posology
No sex-specific data
For MCL, acalabrutinib is given at 100 mg orally twice daily, either as monotherapy in relapsed or refractory disease or in combination with bendamustine and rituximab in previously untreated patients, and is continued until disease progression or unacceptable toxicity; BR is administered for 6 cycles with optional rituximab maintenance in responders.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific differences in adverse reaction profiles were reported in MCL studies.
Pregnancy / lactation
Men
N / A
Women
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.
Sex-specific non-clinical findings
Non-clinical data show no adverse effects of acalabrutinib on male or female rat fertility, and pharmacokinetic analyses indicate that sex does not meaningfully affect acalabrutinib or ACP-5862 exposure.
General information
General Efficacy
Not reported
General Posology
Not reported
Further Dose Adjustments
Not reported
Possible Side Effects
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.
Contraindications
Not reported
Clinical Trial Type and Population
Not reported
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