Previously untreated chronic lymphocytic leukaemia (CLL)

Active Ingredient: Ofatumumab

Indication for Ofatumumab

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

Ofatumumab in combination with chlorambucil or bendamustine is indicated for the treatment of adult patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

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

300 mg on day 1 and 8 of cycle 1 followed by 1,000 mg on day 1 of every cycle, up to maximum of 12 cycles in total

For:

Dosage regimens

For cycle 1, intravenous, 300 milligrams ofatumumab, one dose, over the duration of 7 days. Afterwards, for cycle 1, intravenous, 1,000 milligrams ofatumumab, one dose, over the duration of 21 days. Afterwards, from cycle 2 until cycle 12, intravenous, 1,000 milligrams ofatumumab, one dose, over the duration of 28 days.

Detailed description

Monitoring

Patients should be closely monitored during administration of ofatumumab for the onset of infusion-related reactions, including cytokine release syndrome, particularly during the first infusion.

Pre-medication

Patients should receive the following pre-medication medicinal products 30 minutes to 2 hours prior to each ofatumumab infusion according to the following dosing schedules:

Premedication schedule for ofatumumab:

 Previously untreated CLL
Infusion number1 and 23 to n*
Intravenous corticosteroid (prednisolone or equivalent)50 mg0 to 50 mg**
Oral paracetamol (acetaminophen)1000 mg
Oral or intravenous antihistamineDiphenhydramine 50 mg or cetirizine 10 mg (or equivalent)

* Up to 13 infusions in previously untreated CLL.
** Corticosteroid may be either reduced or omitted for subsequent infusions at the discretion of the physician, if a severe infusion-related adverse drug reaction (ADR) did not occur with the preceding infusion(s).

Posology

For previously untreated CLL, the recommended dosage and schedule is:

  • Cycle 1: 300 mg on day 1 followed 1 week later by 1000 mg on day 8.
  • Subsequent cycles (until best response or a maximum of 12 cycles): 1000 mg on day 1 every 28 days.

Each cycle lasts 28 days and is counted from day 1 of the cycle.

Best response is a clinical response that did not improve with 3 additional cycles of treatment.

First infusion

The initial rate of the first infusion of ofatumumab should be 12 ml/h. During infusion, the rate should be increased every 30 minutes to a maximum of 400 ml/h.

Subsequent infusions

If the preceding infusion(s) has (have) been completed without severe infusion related ADRs, the subsequent infusions can start at a rate of 25 ml/h and should be increased every 30 minutes up to a maximum of 400 ml/h.

Dose modification and reinitiation of therapy after infusion-related ADRs

In the event of a mild or moderate ADR, the infusion should be interrupted and restarted at half of the infusion rate at the time of interruption once the patient's condition is stable. If the infusion rate had not been increased from the starting rate of 12 ml/hour prior to interrupting due to an ADR, the infusion should be restarted at 12 ml/hour, the standard starting infusion rate. The infusion rate can continue to be increased according to standard procedures, to physician discretion and to patient tolerance (not to exceed doubling the rate every 30 minutes).

In the event of a severe ADR, the infusion should be interrupted and restarted at 12 ml/hour when the patient's condition is stable. The infusion rate can continue to be increased according to standard procedures, to physician discretion and to patient tolerance (not to exceed increasing the rate every 30 minutes).

Ofatumumab should be permanently discontinued in patients who develop an anaphylactic reaction.

Active ingredient

Ofatumumab

Ofatumumab is a fully human anti-CD20 monoclonal immunoglobulin G1 (IgG1) antibody. The binding of ofatumumab to CD20 induces lysis of CD20+ B cells primarily through complement-dependent cytotoxicity (CDC) and, to a lesser extent, through antibody-dependent cell-mediated cytotoxicity (ADCC).

Read more about Ofatumumab

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