Chronic lymphocytic leukaemia (CLL)

Active Ingredient: Obinutuzumab

Indication for Obinutuzumab

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

Obinutuzumab in combination with chlorambucil is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy.

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

100 mg on Day 1, 900 mg on Day 2, 1,000 mg on Days 8 and 15 of the first 28 day treatment cycle, followed by 1,000 mg on Day 1 of cycles 2-6

For:

Dosage regimens

Intravenous, 100 milligrams obinutuzumab, one dose, over the duration of 1 day. Afterwards, intravenous, 900 milligrams obinutuzumab, one dose, over the duration of 6 days. Afterwards, intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 7 days. Afterwards, intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 14 days. Afterwards, intravenous, 1,000 milligrams obinutuzumab, once every 28 days. This step is repeated 5 times.

Detailed description

For patients with CLL the recommended dose of obinutuzumab in combination with chlorambucil is shown in the table below.

Cycle 1

The recommended dose of obinutuzumab in combination with chlorambucil is 1 000 mg administered over Day 1 and Day 2, (or Day 1 continued), and on Day 8 and Day 15 of the first 28 day treatment cycle.

Two infusion bags should be prepared for the infusion on Days 1 and 2 (100 mg for Day 1 and 900 mg for Day 2). If the first bag is completed without modifications of the infusion rate or interruptions, the second bag may be administered on the same day (no dose delay necessary, no repetition of premedication), provided that appropriate time, conditions and medical supervision are available throughout the infusion. If there are any modifications of the infusion rate or interruptions during the first 100 mg the second bag must be administered the following day.

Cycles 2–6

The recommended dose of obinutuzumab in combination with chlorambucil is 1 000 mg administered on Day 1 of each cycle.

Dose of obinutuzumab to be administered during 6 treatment cycles each of 28 days duration for patients with CLL:

CycleDay of treatmentDose of obinutuzumab
Cycle 1Day 1100 mg
Day 2 (or Day 1 continued)900 mg
Day 81 000 mg
Day 151 000 mg
Cycle 2–6Day 11 000 mg

Duration of treatment

Six treatment cycles, each of 28 day duration.

Delayed or missed doses

If a planned dose of obinutuzumab is missed, it should be administered as soon as possible; do not wait until the next planned dose. The planned treatment interval for obinutuzumab should be maintained between doses.

Dose modifications during treatment

No dose reductions of obinutuzumab are recommended.

Dosage considerations

Obinutuzumab is for intravenous use. It should be given as an intravenous infusion through a dedicated line after dilution. Obinutuzumab infusions should not be administered as an intravenous push or bolus.

Instructions on the rate of infusion are shown in the following table.

Chronic lymphocytic leukaemia: Standard infusion rate in the absence of IRRs/hypersensitivity and recommendations in case an IRR occurred with previous infusion:

CycleDay of treatmentRate of infusion
 TThe infusion rate may be escalated provided that
the patient can tolerate it. For management of
IRRs that occur during the infusion, refer to
Management of IRRs.
Cycle 1Day 1
(100 mg)
Administer at 25 mg/hr over 4 hours. Do not
increase the infusion rate
Day 2
(or Day 1 continued)
(900 mg)
If no IRR occurred during the previous infusion,
administer at 50 mg/hr.
The rate of the infusion can be escalated in
increments of 50 mg/hr every 30 minutes to a
maximum rate of 400 mg/hr.

If the patient experienced an IRR during the
previous infusion, start with administration at 25
mg/hr. The rate of infusion can be escalated in
increments up to 50 mg/hr every 30 minutes to a
maximum rate of 400 mg/hr.
Day 8
(1 000 mg)
If no IRR occurred during the previous infusion,
when the final infusion rate was 100 mg/hr or
faster, infusions can be started at a rate of
100 mg/hr and increased by 100 mg/hr
increments every 30 minutes to a maximum of
400 mg/hr.
If the patient experienced an IRR during the
previous infusion administer at 50 mg/hr. The
rate of the infusion can be escalated in
increments of 50 mg/hr every 30 minutes to a
maximum rate of 400 mg/hr.
Day 15
(1 000 mg)
Cycles 2-6Day 1
(1 000 mg)

Management of IRRs

Management of IRRs may require temporary interruption, reduction in the rate of infusion, or treatment discontinuations of obinutuzumab as outlined below.

Chronic lymphocytic leukaemia (CLL):

  • Grade 4 (life threatening): Infusion must be stopped and therapy must be permanently discontinued.
  • Grade 3 (severe): Infusion must be temporarily stopped and symptoms treated. Upon resolution of symptoms, the infusion can be restarted at no more than half the previous rate (the rate being used at the time that the IRR occurred) and, if the patient does not experience any IRR symptoms, the infusion rate escalation can resume at the increments and intervals as appropriate for the treatment dose. For CLL patients receiving the Day 1 (Cycle 1) dose split over two days, the Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hour, but not increased further. The infusion must be stopped and therapy permanently discontinued if the patient experiences a second occurrence of a Grade 3 IRR.
  • Grade 1-2 (mild to moderate): The infusion rate must be reduced and symptoms treated. Infusion can be continued upon resolution of symptoms and, if the patient does not experience any IRR symptoms, the infusion rate escalation can resume at the increments and intervals as appropriate for the treatment dose. For CLL patients receiving the Day 1 (Cycle 1) dose split over the two days, the Day 1 infusion rate may be increased back up to 25 mg/hr after 1 hour, but not increased further.

Active ingredient

Obinutuzumab

Obinutuzumab is a recombinant monoclonal humanised and glycoengineered Type II anti-CD20 antibody of the IgG1 isotype. It specifically targets the extracellular loop of the CD20 transmembrane antigen on the surface of non-malignant and malignant pre-B and mature B-lymphocytes. Glycoengineering of the Fc part of obinutuzumab results in higher affinity for FcγRIII receptors on immune effector cells such as natural killer cells, macrophages and monocytes as compared to non-glycoengineered antibodies.

Read more about Obinutuzumab

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