Chronic lymphocytic leukaemia (CLL) - combination treatment with ibrutinib

Active Ingredient: Venetoclax

Indication for Venetoclax

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Venclyxto is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) in combination with ibrutinib.

For this indication, competent medicine agencies globally authorize below treatments:

20 mg once daily for 1 week, gradually increased over a period of 5 weeks up to the daily dose of 400 mg

For:

Dosage regimens

Oral, 20 milligrams venetoclax, once daily, over the duration of 1 week. Afterwards, oral, 50 milligrams venetoclax, once daily, over the duration of 1 week. Afterwards, oral, 100 milligrams venetoclax, once daily, over the duration of 1 week. Afterwards, oral, 200 milligrams venetoclax, once daily, over the duration of 1 week. Afterwards, oral, 400 milligrams venetoclax, once daily, over the duration of 1 week.

Until cycle 15 :

Oral, 400 milligrams venetoclax, once daily.

Detailed description

Dose-titration schedule

The starting dose is 20 mg of venetoclax once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg as shown in Table 1.

Table 1. Dose increase schedule in patients with CLL:

WeekVenetoclax daily dose
120 mg
250 mg
3100 mg
4200 mg
5400 mg

The 5-week dose-titration schedule is designed to gradually reduce tumour burden (debulk) and decrease the risk of TLS.

Venetoclax in combination with ibrutinib

Start ibrutinib (420 mg once daily) as a single agent for 3 cycles (1 cycle is 28 days), followed by 12 cycles of venetoclax in combination with ibrutinib. Beginning on Cycle 4 Day 1, administer venetoclax according to the dose-titration schedule (see Table 1). After completing the dose-titration schedule, patients should continue venetoclax 400 mg once daily in combination with ibrutinib 420 mg orally once daily to the last day of Cycle 15.

Refer to the ibrutinib Summary of Product Characteristics for additional information.

Missed dose

If a patient misses a dose of venetoclax within 8 hours of the time it is usually taken, the patient should take the missed dose as soon as possible on the same day. If a patient misses a dose by more than 8 hours, the patient should not take the missed dose and should resume the usual dosing schedule the following day.

If a patient vomits following dosing, no additional dose should be taken that day. The next prescribed dose should be taken at the usual time the following day.

Dosage considerations

Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax.

Active ingredient

Venetoclax

Venetoclax is a potent, selective inhibitor of B-cell lymphoma (BCL)-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumour cell survival and has been associated with resistance to chemotherapeutics. Venetoclax binds directly to the BH3-binding groove of BCL-2, displacing BH3 motif-containing pro-apoptotic proteins like BIM, to initiate mitochondrial outer membrane permeabilization (MOMP), caspase activation, and programmed cell death.

Read more about Venetoclax

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