Calquence for mantle cell lymphoma and chronic lymphocytic leukemia treatment

Calquence (acalabrutinib) is an oral kinase inhibitor approved for the treatment of certain types of adult blood cancers, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). It can be used alone or in combination with other chemotherapy or immunotherapy agents, depending on the specific condition and treatment history.

Calquence is indicated for the treatment of adult patients with the following conditions:

• Previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation, when used in combination with bendamustine and rituximab.
• Mantle cell lymphoma (MCL) in patients who have received at least one prior therapy.
• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), either as monotherapy or in combination with obinutuzumab or venetoclax for previously untreated patients.

acalabrutinib

Calquence works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme involved in the signaling pathways that promote the growth and survival of certain cancerous B cells in blood cancers like MCL, CLL, and SLL. By blocking BTK activity, Calquence disrupts these signals, thereby helping to slow or stop the progression of cancer.

General dosing instructions

• The recommended dose of Calquence is 100 mg orally approximately every 12 hours.
• Swallow tablets whole with water; do not chew, crush, dissolve, or cut them.
• Calquence can be taken with or without food.
• If a dose is missed by more than 3 hours, skip that dose and take the next dose at the usual scheduled time; do not take extra tablets to make up for a missed dose.

Monotherapy

For MCL, CLL, or SLL patients, take 100 mg orally every 12 hours until disease progression or unacceptable toxicity.

Combination therapies

• With bendamustine and rituximab (for previously untreated MCL patients ineligible for stem cell transplant): Start Calquence on Day 1 of Cycle 1 (28-day cycle), continuing until progression or unacceptable toxicity. Bendamustine 90 mg/m2 is given on Days 1 and 2, and rituximab 375 mg/m2 on Day 1 of Cycle 1 for 6 cycles. Responding patients may receive maintenance rituximab every other cycle for up to 12 additional doses (Cycles 8–30).
• With obinutuzumab (for previously untreated CLL or SLL): Start Calquence at Cycle 1, take 100 mg every 12 hours. Begin obinutuzumab at Cycle 2 for 6 cycles. Administer Calquence prior to obinutuzumab on the same day.
• With venetoclax (for previously untreated CLL or SLL): Start Calquence at Cycle 1, 100 mg every 12 hours. Begin venetoclax at Cycle 3 with a 5-week ramp-up dose schedule starting at 20 mg daily up to 400 mg daily for 12 cycles, following venetoclax prescribing information.

Dose adjustments with CYP3A interactions

• Avoid coadministration with strong CYP3A inhibitors; interrupt Calquence if short-term use of strong inhibitors is needed, then resume 24 hours after stopping inhibitor.
• Reduce dose to 100 mg once daily if taking moderate CYP3A inhibitors.
• Avoid coadministration with strong CYP3A inducers; if unavoidable, increase Calquence dose to 200 mg every 12 hours.

Dose modifications for adverse reactions

Adjust dose based on severity and recurrence of toxicities, including hematologic (e.g., neutropenia, thrombocytopenia) and non-hematologic adverse reactions. Options include temporary interruption, dose reduction to 100 mg once daily, or discontinuation after multiple recurrences or severe toxicity. Specific guidance is provided for Calquence alone or in combination with bendamustine and rituximab or venetoclax, focusing on hematologic toxicities and other serious adverse events.

Serious infections

Calquence may increase the risk of serious and opportunistic infections. Monitor closely and manage promptly.

Hematologic toxicities

Neutropenia and thrombocytopenia have been observed and may require dose adjustment, treatment interruption, or discontinuation.

Common side effects are not exhaustively listed in the provided evidence. Serious adverse reactions may include infections, bleeding events, neutropenia, thrombocytopenia, and tumor lysis syndrome in combination with venetoclax. Adverse reactions may require dose interruptions or modifications.

CYP3A inhibitors and inducers

• Strong CYP3A inhibitors: Avoid co-administration; interrupt Calquence if short-term inhibitor use is necessary.
• Moderate CYP3A inhibitors: Reduce Calquence dose to 100 mg once daily.
• Strong CYP3A inducers: Avoid co-administration; if unavoidable, increase Calquence dose to 200 mg every 12 hours.