Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: AstraZeneca AB, SE-151 85 Södertälje, Sweden
Calquence as monotherapy or in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
Calquence as monotherapy is indicated for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy.
Calquence in combination with bendamustine and rituximab (BR) is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are not eligible for autologous stem cell transplant (ASCT).
Calquence as monotherapy is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) not previously treated with a BTK inhibitor.
Treatment with this medicinal product should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
The recommended dose of Calquence in monotherapy or in combination with other medicinal products is 100 mg acalabrutinib twice daily (equivalent to a total daily dose of 200 mg).
The dose interval is approximately 12 hours.
Treatment with Calquence should be continued until disease progression or unacceptable toxicity.
For the combination regimens, refer to the prescribing information of each of the medicinal product for their dosing information (for details of the combination regimens, see section 5.1).
Calquence should be administered on Day 1 on Cycle 1 (each cycle is 28 days) until disease progression or unacceptable toxicity. Bendamustine should be administered at 90 mg/m² on Days 1 and 2 of each cycle for a total of 6 cycles. Rituximab should be administered at 375 mg/m² on Day 1 each cycle for a total of 6 cycles. Patients achieving a response (partial response [PR] or complete response [CR]) after the first 6 cycles, may receive maintenance rituximab at 375 mg/m² on Day 1 of every other cycle for a maximum of 12 additional doses, starting on Cycle 8 up to Cycle 30.
Recommended dose modifications of Calquence for Grade ≥ 3 adverse reactions in patients receiving Calquence monotherapy and Calquence in combination with obinutuzumab are provided in Table 1.
Recommended dose modifications for Grade ≥ 3 adverse reactions in patients receiving Calquence in combination with bendamustine and rituximab are provided in Table 2.
Table 1. Recommended dose adjustments for adverse reactions*:
| Adverse reaction | Adverse reaction occurrence | Dose modification (Starting dose = 100 mg approximately every 12 hours) |
|---|---|---|
| Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia Or Grade 4 neutropenia lasting longer than 7 days Grade 3 or greater non- haematological toxicities | First and second | Interrupt Calquence Once toxicity has resolved to Grade 1 or baseline, Calquence may be resumed at 100 mg approximately every 12 hours |
| Third | Interrupt Calquence Once toxicity has resolved to Grade 1 or baseline, Calquence may be resumed at a reduced frequency of 100 mg once daily | |
| Fourth | Discontinue Calquence |
* Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Table 2. Recommended dose adjustments for Grade ≥ 3 adverse reactions* in patients receiving Calquence in combination with bendamustine and rituximab:
| Adverse reaction | Bendamustine dose modification† | Calquence dose modification |
|---|---|---|
| Neutropenia | If Grade 3 or Grade 4 neutropenia‡: Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline level, bendamustine may be resumed at 70 mg/m². Discontinue bendamustine if additional dose reduction is required. | If Grade 4 neutropenia lasting longer than 7 days then interrupt Calquence. Once toxicity has resolved to Grade ≤ 2 or baseline level, Calquence may be resumed at starting dose (1st adverse reaction occurrence) or at a reduced frequency of 100 mg once daily (2nd and 3rd adverse reaction occurrence).¶ Discontinue Calquence at 4th adverse reaction occurrence. |
| Thrombocytopenia | If Grade 3 or Grade 4 thrombocytopenia: Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline level, bendamustine may be resumed at 70 mg/m². Discontinue bendamustine if additional dose reduction is required. | If Grade 3 thrombocytopenia with significant bleeding or Grade 4 then interrupt Calquence. Once toxicity has resolved to Grade ≤ 2 or baseline level, Calquence may be resumed at starting dose (1st adverse reaction occurrence) or at a reduced frequency of 100 mg once daily (2nd and 3rd occurrence).¶ Discontinue Calquence at 3rd adverse reaction occurrence for thrombocytopenia with significant bleeding. Discontinue Calquence at 4th adverse reaction occurrence. |
| Other hematologic Grade 4§ or unmanageable Grade 3 toxicity | Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline level, bendamustine may be resumed at 70 mg/m². Discontinue bendamustine if additional dose reduction is required. | Interrupt Calquence. Once toxicity has resolved to Grade ≤ 2 or baseline level, Calquence may be resumed at starting dose (1st adverse reaction occurrence) or at a reduced frequency of 100 mg once daily (2nd and 3rd adverse reaction occurrence).¶ Discontinue Calquence at 4th adverse reaction occurrence. |
| Grade 3 or greater non-hematologic toxicities | Interrupt bendamustine. Once toxicity has resolved to Grade 1 or baseline level, bendamustine may be resumed at 70 mg/m². Discontinue bendamustine if additional dose reduction is required. | Interrupt Calquence. Once toxicity has resolved to Grade 2 or baseline, Calquence may be resumed at starting dose (1st adverse reaction occurrence) or at a reduced frequency of 100 mg once daily (2nd adverse reaction occurrence).¶ Discontinue Calquence at 3rd adverse reaction occurrence. |
* Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
† For any toxicities not listed in this table refer to the bendamustine local prescribing information.
‡ Consider use of myeloid growth factors before bendamustine dose modifications.
§ Grade 4 lymphopenia is an expected outcome for treatment with bendamustine and rituximab. Dose modification due to lymphopenia is expected only if considered clinically important by investigators e.g. associated recurrent infections.
¶ Dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks.
Refer to the prescribing information of each of the medicinal products used in combination with Calquence for additional information for management of toxicities.
Recommendations regarding use of Calquence with CYP3A inhibitors or inducers and gastric acid reducing agents are provided in Table 3 (see section 4.5).
Table 3. Use with CYP3A inhibitors or inducers and gastric acid reducing agents:
| Co-administered medicinal product | Recommended Calquence use | |
|---|---|---|
| CYP3A inhibitors | Strong CYP3A inhibitor | Avoid concomitant use. If these inhibitors will be used short-term (such as anti-infectives for up to seven days), interrupt Calquence. |
| Moderate CYP3A inhibitor | No dose adjustment. Monitor patients closely for adverse reactions if taking moderate CYP3A inhibitors. | |
| Mild CYP3A inhibitor | No dose adjustment. | |
| CYP3A inducers | Strong CYP3A inducer | Avoid concomitant use. |
| Gastric acid reducing agents | Proton pump inhibitors | Avoid concomitant use. |
| H2-receptor antagonists | Take Calquence 2 hours before (or 10 hours after) taking a H2-receptor antagonist. | |
| Antacids | The interval between taking the medicinal products should be at least 2 hours. |
If a patient misses a dose of Calquence by more than 3 hours, the patient should be instructed to take the next dose at its regularly scheduled time. Double dose of Calquence should not be taken to make up for a missed dose.
No dose adjustment is required for elderly patients (aged ≥ 65 years) (see section 5.2).
No specific clinical studies have been conducted in patients with renal impairment. Patients with mild or moderate renal impairment were treated in Calquence clinical studies. No dose adjustment is needed for patients with mild or moderate renal impairment (greater than 30 mL/min creatinine clearance). Hydration should be maintained, and serum creatinine levels monitored periodically. Calquence should be administered to patients with severe renal impairment (< 30mL/min creatinine clearance) only if the benefit outweighs the risk and these patients should be monitored closely for signs of toxicity. There are no data in patients with severe renal impairment or patients on dialysis (see section 5.2).
No dose adjustment is recommended in patients with mild or moderate hepatic impairment (Child-Pugh A, Child-Pugh B, or total bilirubin between 1.5-3 times the upper limit of normal [ULN] and any AST). However, patients with moderate hepatic impairment should be closely monitored for signs of toxicity. It is not recommended to use Calquence in patients with severe hepatic impairment (Child-Pugh C or total bilirubin >3-times ULN and any AST) (see section 5.2).
Patients with severe cardiovascular disease were excluded from Calquence clinical studies.
The safety and efficacy of Calquence in children and adolescents aged 0 to 18 years have not been established. No data are available.
Calquence is for oral use. The capsules should be swallowed whole with water at approximately the same time each day, with or without food (see section 4.5). The capsules should not be chewed, dissolved or opened as this may affect the absorption of the medicinal product into the body.
There is no specific treatment for acalabrutinib overdose and symptoms of overdose have not been established. In the event of an overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.
3 years.
This medicinal product does not require any special storage conditions.
Aluminium/Aluminium blisters with sun/moon symbols containing 6 or 8 hard capsules. Cartons of 56 or 60 capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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