Acalabrutinib
Acalabrutinib is an oral therapy for adult haematologic malignancies, including 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 differences in potential side effects
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
65.3%
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity. When combined with obinutuzumab, use the labelled obinutuzumab schedule.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
N / A
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
Disease prevalence by sex
Men
65.3%
Women
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity. When combined with obinutuzumab, use the labelled obinutuzumab schedule.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
Men
N / A
Women
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
General information
General Efficacy
Primary endpoints: Primary efficacy endpoints were progression-free survival (PFS) by Independent Review Committee in the Phase 3 studies ELEVATE-TN, AMPLIFY, ASCEND and ECHO, using disease-specific response criteria; in ACE-LY-004 for previously treated MCL, the primary endpoint was investigator-assessed overall response rate (ORR) per Lugano classification. Secondary endpoints: Key supportive endpoints included overall survival, best overall response rate/overall response rate, complete and partial response rates, and duration of response. In AMPLIFY, additional efficacy endpoints were IRC-assessed PFS of AVO versus investigator’s choice chemoimmunotherapy and overall survival in both AV and AVO versus investigator’s choice.
General Posology
Recommended dose: acalabrutinib 100 mg orally twice daily, approximately 12 hours apart, swallowed whole with water, with or without food. Monotherapy or combination with obinutuzumab is continued until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab, acalabrutinib starts on Day 1 Cycle 1 for 14 cycles; venetoclax starts on Day 1 Cycle 3 for 12 cycles with weekly escalation 20 mg, 50 mg, 100 mg, 200 mg, then 400 mg; if obinutuzumab is added, give 100 mg on Day 1 of Cycle 2, then 900 mg on Day 1 or 2, then 1 000 mg on Days 8 and 15 of Cycle 2 and Day 1 of Cycles 3 to 7. With bendamustine and rituximab, acalabrutinib starts Day 1 Cycle 1 until disease progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 for 6 cycles, rituximab 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab 375 mg/m2 every other cycle for up to 12 additional doses.
Further Dose Adjustments
Hypersensitivity to acalabrutinib or any excipients.
Possible Side Effects
Across regimens, very common adverse reactions included infection/infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea, rash, leukopenia, neutropenia, constipation, vomiting, anaemia and thrombocytopenia. Frequently reported Grade 3 or higher or serious reactions included infection, leukopenia, neutropenia, anaemia, thrombocytopenia, pneumonia, second primary malignancies and hypertension. Severe infections were reported with venetoclax combinations. Main reasons for discontinuation included pneumonia, thrombocytopenia, diarrhoea, COVID-19/COVID-19 pneumonia, neutropenia and nausea.
Contraindications
Hypersensitivity to acalabrutinib or any excipients.
Clinical Trial Type and Population
Clinical efficacy and safety were evaluated in adult patients with CLL or MCL across four Phase 3 studies and one Phase 2 study supporting the relapsed/refractory MCL indication. ELEVATE-TN: n=535, median age 70-71 years, women about 38-40% by arm; AMPLIFY: n=867, median age 61 years, women about 31-39% by arm; ASCEND: n=310, median age 67-68 years, women about 30-36% by arm; ECHO: n=598, median age 71 years, 29.3% women; ACE-LY-004: n=124, median age 68 years, 20.2% women.
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex differences in potential side effects
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
65.3%
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, starting on Day 1 of Cycle 1 for 14 cycles. Venetoclax starts on Day 1 of Cycle 3 for 12 cycles with weekly escalation to 400 mg; if used, obinutuzumab starts in Cycle 2 and continues through Cycle 7.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
N / A
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
Disease prevalence by sex
Men
65.3%
Women
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, starting on Day 1 of Cycle 1 for 14 cycles. Venetoclax starts on Day 1 of Cycle 3 for 12 cycles with weekly escalation to 400 mg; if used, obinutuzumab starts in Cycle 2 and continues through Cycle 7.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
Men
N / A
Women
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
General information
General Efficacy
Primary endpoints: Primary efficacy endpoints were progression-free survival (PFS) by Independent Review Committee in the Phase 3 studies ELEVATE-TN, AMPLIFY, ASCEND and ECHO, using disease-specific response criteria; in ACE-LY-004 for previously treated MCL, the primary endpoint was investigator-assessed overall response rate (ORR) per Lugano classification. Secondary endpoints: Key supportive endpoints included overall survival, best overall response rate/overall response rate, complete and partial response rates, and duration of response. In AMPLIFY, additional efficacy endpoints were IRC-assessed PFS of AVO versus investigator’s choice chemoimmunotherapy and overall survival in both AV and AVO versus investigator’s choice.
General Posology
Recommended dose: acalabrutinib 100 mg orally twice daily, approximately 12 hours apart, swallowed whole with water, with or without food. Monotherapy or combination with obinutuzumab is continued until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab, acalabrutinib starts on Day 1 Cycle 1 for 14 cycles; venetoclax starts on Day 1 Cycle 3 for 12 cycles with weekly escalation 20 mg, 50 mg, 100 mg, 200 mg, then 400 mg; if obinutuzumab is added, give 100 mg on Day 1 of Cycle 2, then 900 mg on Day 1 or 2, then 1 000 mg on Days 8 and 15 of Cycle 2 and Day 1 of Cycles 3 to 7. With bendamustine and rituximab, acalabrutinib starts Day 1 Cycle 1 until disease progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 for 6 cycles, rituximab 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab 375 mg/m2 every other cycle for up to 12 additional doses.
Further Dose Adjustments
Hypersensitivity to acalabrutinib or any excipients.
Possible Side Effects
Across regimens, very common adverse reactions included infection/infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea, rash, leukopenia, neutropenia, constipation, vomiting, anaemia and thrombocytopenia. Frequently reported Grade 3 or higher or serious reactions included infection, leukopenia, neutropenia, anaemia, thrombocytopenia, pneumonia, second primary malignancies and hypertension. Severe infections were reported with venetoclax combinations. Main reasons for discontinuation included pneumonia, thrombocytopenia, diarrhoea, COVID-19/COVID-19 pneumonia, neutropenia and nausea.
Contraindications
Hypersensitivity to acalabrutinib or any excipients.
Clinical Trial Type and Population
Clinical efficacy and safety were evaluated in adult patients with CLL or MCL across four Phase 3 studies and one Phase 2 study supporting the relapsed/refractory MCL indication. ELEVATE-TN: n=535, median age 70-71 years, women about 38-40% by arm; AMPLIFY: n=867, median age 61 years, women about 31-39% by arm; ASCEND: n=310, median age 67-68 years, women about 30-36% by arm; ECHO: n=598, median age 71 years, 29.3% women; ACE-LY-004: n=124, median age 68 years, 20.2% women.
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex differences in potential side effects
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
65.3%
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
N / A
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
Disease prevalence by sex
Men
65.3%
Women
34.7%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
Men
N / A
Women
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
General information
General Efficacy
Primary endpoints: Primary efficacy endpoints were progression-free survival (PFS) by Independent Review Committee in the Phase 3 studies ELEVATE-TN, AMPLIFY, ASCEND and ECHO, using disease-specific response criteria; in ACE-LY-004 for previously treated MCL, the primary endpoint was investigator-assessed overall response rate (ORR) per Lugano classification. Secondary endpoints: Key supportive endpoints included overall survival, best overall response rate/overall response rate, complete and partial response rates, and duration of response. In AMPLIFY, additional efficacy endpoints were IRC-assessed PFS of AVO versus investigator’s choice chemoimmunotherapy and overall survival in both AV and AVO versus investigator’s choice.
General Posology
Recommended dose: acalabrutinib 100 mg orally twice daily, approximately 12 hours apart, swallowed whole with water, with or without food. Monotherapy or combination with obinutuzumab is continued until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab, acalabrutinib starts on Day 1 Cycle 1 for 14 cycles; venetoclax starts on Day 1 Cycle 3 for 12 cycles with weekly escalation 20 mg, 50 mg, 100 mg, 200 mg, then 400 mg; if obinutuzumab is added, give 100 mg on Day 1 of Cycle 2, then 900 mg on Day 1 or 2, then 1 000 mg on Days 8 and 15 of Cycle 2 and Day 1 of Cycles 3 to 7. With bendamustine and rituximab, acalabrutinib starts Day 1 Cycle 1 until disease progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 for 6 cycles, rituximab 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab 375 mg/m2 every other cycle for up to 12 additional doses.
Further Dose Adjustments
Hypersensitivity to acalabrutinib or any excipients.
Possible Side Effects
Across regimens, very common adverse reactions included infection/infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea, rash, leukopenia, neutropenia, constipation, vomiting, anaemia and thrombocytopenia. Frequently reported Grade 3 or higher or serious reactions included infection, leukopenia, neutropenia, anaemia, thrombocytopenia, pneumonia, second primary malignancies and hypertension. Severe infections were reported with venetoclax combinations. Main reasons for discontinuation included pneumonia, thrombocytopenia, diarrhoea, COVID-19/COVID-19 pneumonia, neutropenia and nausea.
Contraindications
Hypersensitivity to acalabrutinib or any excipients.
Clinical Trial Type and Population
Clinical efficacy and safety were evaluated in adult patients with CLL or MCL across four Phase 3 studies and one Phase 2 study supporting the relapsed/refractory MCL indication. ELEVATE-TN: n=535, median age 70-71 years, women about 38-40% by arm; AMPLIFY: n=867, median age 61 years, women about 31-39% by arm; ASCEND: n=310, median age 67-68 years, women about 30-36% by arm; ECHO: n=598, median age 71 years, 29.3% women; ACE-LY-004: n=124, median age 68 years, 20.2% women.
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex differences in potential side effects
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
75%
25%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity; bendamustine is given at 90 mg/m2 on Days 1 and 2 for 6 cycles and rituximab at 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab every other cycle for up to 12 additional doses.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
N / A
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
Disease prevalence by sex
Men
75%
Women
25%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity; bendamustine is given at 90 mg/m2 on Days 1 and 2 for 6 cycles and rituximab at 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab every other cycle for up to 12 additional doses.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
Men
N / A
Women
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
General information
General Efficacy
Primary endpoints: Primary efficacy endpoints were progression-free survival (PFS) by Independent Review Committee in the Phase 3 studies ELEVATE-TN, AMPLIFY, ASCEND and ECHO, using disease-specific response criteria; in ACE-LY-004 for previously treated MCL, the primary endpoint was investigator-assessed overall response rate (ORR) per Lugano classification. Secondary endpoints: Key supportive endpoints included overall survival, best overall response rate/overall response rate, complete and partial response rates, and duration of response. In AMPLIFY, additional efficacy endpoints were IRC-assessed PFS of AVO versus investigator’s choice chemoimmunotherapy and overall survival in both AV and AVO versus investigator’s choice.
General Posology
Recommended dose: acalabrutinib 100 mg orally twice daily, approximately 12 hours apart, swallowed whole with water, with or without food. Monotherapy or combination with obinutuzumab is continued until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab, acalabrutinib starts on Day 1 Cycle 1 for 14 cycles; venetoclax starts on Day 1 Cycle 3 for 12 cycles with weekly escalation 20 mg, 50 mg, 100 mg, 200 mg, then 400 mg; if obinutuzumab is added, give 100 mg on Day 1 of Cycle 2, then 900 mg on Day 1 or 2, then 1 000 mg on Days 8 and 15 of Cycle 2 and Day 1 of Cycles 3 to 7. With bendamustine and rituximab, acalabrutinib starts Day 1 Cycle 1 until disease progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 for 6 cycles, rituximab 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab 375 mg/m2 every other cycle for up to 12 additional doses.
Further Dose Adjustments
Hypersensitivity to acalabrutinib or any excipients.
Possible Side Effects
Across regimens, very common adverse reactions included infection/infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea, rash, leukopenia, neutropenia, constipation, vomiting, anaemia and thrombocytopenia. Frequently reported Grade 3 or higher or serious reactions included infection, leukopenia, neutropenia, anaemia, thrombocytopenia, pneumonia, second primary malignancies and hypertension. Severe infections were reported with venetoclax combinations. Main reasons for discontinuation included pneumonia, thrombocytopenia, diarrhoea, COVID-19/COVID-19 pneumonia, neutropenia and nausea.
Contraindications
Hypersensitivity to acalabrutinib or any excipients.
Clinical Trial Type and Population
Clinical efficacy and safety were evaluated in adult patients with CLL or MCL across four Phase 3 studies and one Phase 2 study supporting the relapsed/refractory MCL indication. ELEVATE-TN: n=535, median age 70-71 years, women about 38-40% by arm; AMPLIFY: n=867, median age 61 years, women about 31-39% by arm; ASCEND: n=310, median age 67-68 years, women about 30-36% by arm; ECHO: n=598, median age 71 years, 29.3% women; ACE-LY-004: n=124, median age 68 years, 20.2% women.
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex differences in potential side effects
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
75%
25%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
N / A
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
Disease prevalence by sex
Men
75%
Women
25%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
No sex-specific efficacy differences were reported.
Sex-specific posology
No sex-specific data
Acalabrutinib 100 mg orally twice daily, about 12 hours apart, swallowed whole with water, with or without food; continue until disease progression or unacceptable toxicity.
Sex-specific differences in possible side effects
No sex differences in data
No sex-specific differences in adverse reactions were reported.
Pregnancy / lactation
Men
N / A
Women
Avoid pregnancy during acalabrutinib treatment. Acalabrutinib should not be used during pregnancy unless clinically necessary; animal data suggest fetal risk. Breast-feeding should be avoided during treatment and for 2 days after the last dose.
Sex-specific non-clinical findings
Sex did not have clinically meaningful effects on pharmacokinetics. No human fertility data are available; no adverse effects on fertility parameters were seen in male and female rats.
General information
General Efficacy
Primary endpoints: Primary efficacy endpoints were progression-free survival (PFS) by Independent Review Committee in the Phase 3 studies ELEVATE-TN, AMPLIFY, ASCEND and ECHO, using disease-specific response criteria; in ACE-LY-004 for previously treated MCL, the primary endpoint was investigator-assessed overall response rate (ORR) per Lugano classification. Secondary endpoints: Key supportive endpoints included overall survival, best overall response rate/overall response rate, complete and partial response rates, and duration of response. In AMPLIFY, additional efficacy endpoints were IRC-assessed PFS of AVO versus investigator’s choice chemoimmunotherapy and overall survival in both AV and AVO versus investigator’s choice.
General Posology
Recommended dose: acalabrutinib 100 mg orally twice daily, approximately 12 hours apart, swallowed whole with water, with or without food. Monotherapy or combination with obinutuzumab is continued until disease progression or unacceptable toxicity. With venetoclax with or without obinutuzumab, acalabrutinib starts on Day 1 Cycle 1 for 14 cycles; venetoclax starts on Day 1 Cycle 3 for 12 cycles with weekly escalation 20 mg, 50 mg, 100 mg, 200 mg, then 400 mg; if obinutuzumab is added, give 100 mg on Day 1 of Cycle 2, then 900 mg on Day 1 or 2, then 1 000 mg on Days 8 and 15 of Cycle 2 and Day 1 of Cycles 3 to 7. With bendamustine and rituximab, acalabrutinib starts Day 1 Cycle 1 until disease progression or unacceptable toxicity; bendamustine 90 mg/m2 on Days 1 and 2 for 6 cycles, rituximab 375 mg/m2 on Day 1 for 6 cycles, with optional maintenance rituximab 375 mg/m2 every other cycle for up to 12 additional doses.
Further Dose Adjustments
Hypersensitivity to acalabrutinib or any excipients.
Possible Side Effects
Across regimens, very common adverse reactions included infection/infections, diarrhoea, headache, musculoskeletal pain, bruising, cough, arthralgia, fatigue, nausea, rash, leukopenia, neutropenia, constipation, vomiting, anaemia and thrombocytopenia. Frequently reported Grade 3 or higher or serious reactions included infection, leukopenia, neutropenia, anaemia, thrombocytopenia, pneumonia, second primary malignancies and hypertension. Severe infections were reported with venetoclax combinations. Main reasons for discontinuation included pneumonia, thrombocytopenia, diarrhoea, COVID-19/COVID-19 pneumonia, neutropenia and nausea.
Contraindications
Hypersensitivity to acalabrutinib or any excipients.
Clinical Trial Type and Population
Clinical efficacy and safety were evaluated in adult patients with CLL or MCL across four Phase 3 studies and one Phase 2 study supporting the relapsed/refractory MCL indication. ELEVATE-TN: n=535, median age 70-71 years, women about 38-40% by arm; AMPLIFY: n=867, median age 61 years, women about 31-39% by arm; ASCEND: n=310, median age 67-68 years, women about 30-36% by arm; ECHO: n=598, median age 71 years, 29.3% women; ACE-LY-004: n=124, median age 68 years, 20.2% women.
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