Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: AstraZeneca AB, SE-151 85 Södertälje, Sweden
Lumoxiti as monotherapy is indicated for the treatment of adult patients with relapsed or refractory hairy cell leukaemia (HCL) after receiving at least two prior systemic therapies, including treatment with a purine nucleoside analogue (PNA).
Treatment should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
The recommended dose of Lumoxiti is 0.04 mg/kg administered as a 30-minute intravenous infusion on Days 1, 3, and 5 of each 28-day cycle. Patients should continue treatment for a maximum of 6 cycles, or until disease progression or unacceptable toxicity. Treatment may be stopped at the physician’s discretion if complete response (CR) without minimal residual disease (MRD) is achieved prior to the completion of 6 cycles.
In patients over 50 kg, 1 L isotonic solution (e.g. dextrose 50 mg/mL [5%] and sodium chloride 9 mg/mL [0.9%] or 4.5 mg/mL [0.45%] solution for injection) should be administered intravenously over 2-4 hours before and after each Lumoxiti infusion. Patients under 50 kg require 0.5 L to be administered.
Patients should be adequately hydrated. Patients are advised to drink 3 L of oral fluids per 24 hours on Days 1 through 8 of each 28-day cycle. In patients under 50 kg, 2 L per day is recommended.
Fluid balance should be monitored to avoid fluid overload (see section 4.4).
Premedication is required 30-90 minutes prior to each Lumoxiti infusion with an oral antihistamine (e.g. hydroxyzine or diphenhydramine), an antipyretic (e.g. paracetamol), and a histamine-2 receptor antagonist (e.g. ranitidine, famotidine, or cimetidine).
If a severe infusion related reaction occurs, see section 4.4 for further instructions.
Lumoxiti treatment must be withheld and/or discontinued to manage adverse reactions as described below.
Haemolytic uraemic syndrome (HUS) and capillary leak syndrome (CLS) are identified based on clinical presentation (see Table 1).
Table 1. Monitoring for HUS and CLS:
| HUS | CLS | |
|---|---|---|
| Monitoring Parameter | Before every infusion, check: Haemoglobin levels Platelet count Serum creatinine LDH Indirect bilirubin | Before every infusion, check: Weight Blood pressure Albumin |
| Assessment | Consider diagnosis of HUS if: Haemoglobin decreased by 1 g/dL or platelet count <25,000/mm3 unrelated to the underlying disease, and Grade 2 creatinine increase (1.5- to 3-times baseline or the upper limit of normal) If HUS is suspected based on the above, promptly check blood LDH, indirect bilirubin and blood smear schistocytes for evidence of haemolysis. | If weight has increased by ≥10% from Day 1 of the cycle and the patient is hypotensive, promptly check for peripheral oedema, hypoalbuminaemia, and respiratory symptoms, including shortness of breath and cough. If CLS is suspected, check for a decrease in oxygen saturation and evidence of pulmonary oedema and/or serosal effusions. |
Patients who experience Grade 2 or higher HUS should receive appropriate supportive measures and fluid replacement, with monitoring of blood chemistry, complete blood counts, and renal function (includ Medicinal ing monitoring of serum creatinine and/or eGFR) until resolution (see section 4.4).
Table 2. HUS grading and management guidance:
| HUS grade | Lumoxiti dosing |
|---|---|
| Grade 2 Evidence of RBC destruction (schistocytosis) and mild renal insufficiency without clinical consequences | Delay dosing until recovery of haemolysis and serum creatinine to Grade 1 or baseline. Discontinue Lumoxiti upon recurrence. |
| Grade 3 Laboratory findings with clinical consequences (e.g. haemolysis with progressive renal failure, petechiae) | Discontinue Lumoxiti. |
| Grade 4 Life-threatening consequences (e.g. CNS haemorrhage or thrombosis/embolism or renal failure) |
Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Patients who experience Grade 2 or higher CLS should receive appropriate supportive measures including treatment with oral or intravenous corticosteroids, with monitoring of weight, albumin levels, and blood pressure until resolution (see section 4.4).
Table 3. CLS grading and management guidance:
| CLS grade | Lumoxiti dosing |
|---|---|
| Grade 2 Symptomatic; intervention indicated | Delay dosing until recovery of symptoms. |
| Grade 3 Severe symptoms; intervention indicated | Discontinue Lumoxiti. |
| Grade 4 Life-threatening consequences; urgent intervention indicated |
Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
For patients with baseline serum creatinine within normal limits, dosing should be delayed for Grade 2 or higher creatinine increases (greater than 1.5-times baseline or the upper limit of normal). Lumoxiti should be resumed upon recovery to at least Grade 1 (1.0- to 1.5-times baseline, or between the upper limit of normal and 1.5-times the upper limit of normal).
For patients with baseline serum creatinine of Grade 1 or 2, delay dosing for creatinine increases to Grade 3 or higher (greater than 3-times baseline or the upper limit of normal). Lumoxiti should be resumed upon recovery to baseline grade or lower.
Refer to section 4.4 for further monitoring and evaluation information.
No dose adjustment is required for elderly patients (≥65 years of age) (see Renal function monitoring in section 4.4, and Elderly in sections 4.8 and 5.1).
No dose adjustment of Lumoxiti is recommended for patients with mild renal impairment. Data supporting use of moxetumomab pasudotox in moderate renal impairment is limited. Moxetumomab pasudotox has not been studied in patients with severe renal impairment (see Renal function monitoring in section 4.4).
No dose adjustment of Lumoxiti is recommended for patients with mild hepatic impairment. Moxetumomab pasudotox has not been studied in patients with moderate or severe hepatic impairment (see section 5.2).
There is no relevant use of Lumoxiti in children aged 0 to 18 years in the treatment of HCL.
Lumoxiti is for intravenous use.
The diluted solution is administered intravenously over 30 minutes. An infusion set fitted with a sterile, low-protein binding 0.22 micron in-line filter should be used.
After the infusion, the intravenous administration line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection at the same rate as the infusion. This ensures the full Lumoxiti dose is delivered.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
There is no specific treatment for moxetumomab pasudotox overdose. In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted immediately.
Unopened vial: 4 years.
Lumoxiti concentrate (i.e. reconstituted Lumoxiti powder for concentrate): The Lumoxiti concentrate should be immediately further diluted.
From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
Lumoxiti solution (i.e. diluted Lumoxiti concentrate in the prepared infusion bag): Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C-8°C or 4 hours at room temperature up to 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C-8°C, unless dilution has taken place in controlled and validated aseptic conditions.
Store and transport refrigerated (2°C-8°C).
Do not freeze.
Store in the original carton in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
Lumoxiti 1 mg powder for concentrate is provided in a Type 1 glass vial with an elastomeric stopper and a dark blue flip-off aluminium seal.
The 1 mL solution (stabiliser) is provided in a Type 1 glass vial with an elastomeric stopper and a dark grey flip-off aluminium seal.
Each pack contains:
Not all pack sizes may be marketed.
For single use only. Lumoxiti powder for concentrate must be reconstituted and diluted by a healthcare professional using aseptic technique.
Lumoxiti powder for concentrate must be reconstituted with water for injections. Water for injections is not provided in the pack. A solution (stabiliser) is provided inside the Lumoxiti carton and is added to the infusion bag prior to addition of reconstituted powder for concentrate. Do not use this solution (stabiliser) for reconstitution of the powder for concentrate.
Following reconstitution, immediately proceed with the dilution process in Steps 3 and 4. Do not store the Lumoxiti concentrate.
The solution (stabiliser) must be added to the infusion bag only. The solution (stabiliser) must be added to the infusion bag before the Lumoxiti concentrate is added. Only 1 vial of solution (stabiliser) should be used per infusion bag. Any extra vial(s) of solution (stabiliser) should be discarded.
Withdraw the required volume (calculated from Step 1) of Lumoxiti concentrate from the reconstituted vial(s).
Following this dilution step, infuse the Lumoxiti solution (from the final infusion bag) immediately (step 5).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
