Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Kyowa Kirin Holdings B.V., Bloemlaan 2, 2132 NP, Hoofddorp, Netherlands
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients receiving mogamulizumab have experienced drug rash (drug eruption), some of which were severe and/or serious.
When mogamulizumab has been administered to patients with T-cell lymphomas other than MF or SS, serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in less than 1% of patients during clinical trials, and also reported during the post-marketing period; some of these cases were reported with fatal outcomes. Patients should be closely monitored for symptoms or signs that suggest SJS or TEN. If they occur, POTELIGEO should be interrupted and treatment should not restart unless SJS or TEN is ruled out and cutaneous reaction has resolved to Grade 1 or less. If SJS/TEN occur, appropriate medical therapy should be administered. See section 4.2 for dose modification information.
Acute infusion-related reactions (IRRs) have been observed in patients treated with mogamulizumab. The IRRs were mostly mild or moderate in severity, although there have been a few reports of severe reactions (Grade 3). The majority of IRRs occur during or shortly after the first infusion (all within 24 hours of administration), with the incidence decreasing over subsequent treatments.
Patients should be carefully monitored during and after infusion. If an anaphylactic reaction occurs, administration of mogamulizumab should be immediately and permanently discontinued and appropriate medical therapy should be administered.
If an IRR occurs, the infusion should be interrupted and appropriate medical management instituted. The infusion may be restarted at a slower rate after symptom resolution. See section 4.2 for pre-medication and dose modification information.
Subjects with MF or SS treated with mogamulizumab are at increased risk of serious infection and/or viral reactivation. The combination of mogamulizumab with systemic immune modulating medicinal products or with other licensed therapies for MF or SS has not been studied and is, therefore, not recommended, especially in consideration of the risk of severe infections in patients treated with mogamulizumab. Topical steroids or low doses of systemic corticosteroids may be used during treatment with mogamulizumab; however, the risk of serious infection and/or viral reactivation may be higher in case of concomitant administration with systemic immunosuppressive agents. Patients should be monitored for signs and symptoms of infection and treated promptly.
Patients should be tested for hepatitis B infection before initiating treatment with mogamulizumab. For patients who test positive for current/previous hepatitis B infection, consultation with a physician with expertise in the treatment of hepatitis B is recommended for advice concerning appropriate measures against hepatitis B reactivation.
Complications, including severe graft versus host disease (GVHD), have been reported in patients with T-cell lymphomas other than MF or SS who received allogeneic HSCT after mogamulizumab.
A higher risk of transplant complications has been reported if mogamulizumab is given within a short time frame (approximately 50 days) before HSCT. Follow patients closely for early evidence of transplant-related complications.
The safety of treatment with mogamulizumab after autologous or allogeneic HSCT has not been studied.
Tumour lysis syndrome (TLS) has been observed in patients receiving mogamulizumab. TLS was observed most frequently during the first month of treatment. Patients with rapidly proliferating tumour and high tumour burden are at risk of TLS. Patients should be monitored closely by appropriate laboratory and clinical tests for electrolyte status, hydration and renal function, particularly in the first month of treatment, and managed according to best medical practice. Management of TLS may include aggressive hydration, correction of electrolyte abnormalities, anti-hyperuricaemic therapy, and supportive care.
One case of acute myocardial infarction has been observed in a clinical trial patient with MF/SS receiving mogamulizumab. In clinical trial patients with other T-cell lymphomas there have been reports of stress cardiomyopathy (one case) and acute myocardial infarction (one case). The subjects had a medical history including various risk factors. Patients who have risk factors associated with cardiac disease should be monitored and appropriate precautions taken.
There are limited data available on patients with LCT.
Mogamulizumab should not be administered subcutaneously or intramuscularly, by rapid intravenous administration, or as an intravenous bolus.
This medicinal product contains less than 1 mmol sodium per dose, that is to say essentially ‘sodium free’.
No interaction studies have been performed.
Women of childbearing potential and males of reproductive potential should use effective contraception during treatment with POTELIGEO and for at least 6 months after treatment.
There are no data from the use of mogamulizumab in pregnant women. Although mogamulizumab crosses the placental barrier in cynomolgous monkey, apart from the pharmacological effect in foetuses, animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of mogamulizumab during pregnancy.
It is unknown whether mogamulizumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast-fed child cannot be excluded during this short period. Afterwards POTELIGEO could be used during breast-feeding if clinically needed.
There are no clinical data available on the effect of mogamulizumab on human fertility. No specific studies in animals have been performed to evaluate the effect of mogamulizumab on fertility. No adverse effects on male and female reproductive organs were observed in repeat-dose toxicity studies in cynomolgus monkeys (see section 5.3).
Mogamulizumab has minor influence on the ability to drive and use machines. Fatigue may occur following administration of mogamulizumab (see section 4.8).
The most frequently reported serious adverse reactions were pneumonia, pyrexia, infusion related reaction and cellulitis.
The most frequently reported adverse reactions were infusion-related reaction and rash (drug eruption); most of these reactions were non-serious and Grades 1 or 2.
Severe adverse reactions included Grade 4 respiratory failure (1.1%) and Grade 5 reactions were polymyositis and sepsis (0.5% each).
The adverse reactions are presented by system organ class and frequency categories, defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1. Adverse drug reactions occurring in patients receiving POTELIGEO (N=184):
Common: Anaemia, neutropenia, leukopenia, Thrombocytopenia
Common: Hypothyroidism
Very common: Constipation, diarrhoea, nausea, stomatitis
Common: Vomiting
Very common: Fatigue, oedema peripheral, pyrexia
Uncommon: Hepatitis acute, hepatitis
Very common: Infectionsa
Common: Upper respiratory tract infection
Very common: Infusion related reaction
Common: Alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, lymphocyte count decreased
Uncommon: Tumour lysis syndrome
Very common: Headache
Very common: Drug eruption (including skin rash)
a Folliculitis, Cellulitis, Candidiasis, Pneumonia, Sepsis, Skin infection, Otitis externa, Herpes zoster, Staphylococcal skin infection, Urinary tract infection, Herpes simplex and cytomegalovirus
Patients receiving POTELIGEO have experienced drug rash (drug eruption), some of which were severe and/or serious. The majority of treatment-related dermatologic reactions were Grade 1 or 2, with Grade ≥3 drug rash occurring in 4.3% of patients. No trend in latency to event onset was identified for drug eruptions and rashes; both early and late-onset events occurred.
Infusion-related reactions have been observed in 33% of patients treated with POTELIGEO. The majority of treatment-related infusion-related reactions were Grade 1 or 2 and occurred during or shortly after the first infusion. Severe reactions (Grade 3) were experienced by 4% of patients.
The incidence of infusion related reactions was highest after the first infusion (28.8% of subjects), reducing to ≤3.8% of subjects after two or more infusions.
Infusion interruptions occurred in approximately 6% of patients, most of which (approximately 90%) occurred within the first cycle of treatment with mogamulizumab.
Less than 1% of patients treated in Study 0761-010 discontinued treatment due to infusion-related reactions.
Patients with MF or SS are at increased risk of serious infection due to the disruption of dermal integrity caused by cutaneous disease, as well as the immunosuppressive effects of extracutaneous disease, and treatment with mogamulizumab may increase that risk. Serious infections, including sepsis, pneumonia and skin infections, were experienced by 14.3% of subjects receiving mogamulizumab. The latency to event onset following the first dose varied considerably. The majority of patients recovered from infection. In the clinical trial (0761-010), there were 2 reports of respiratory failure with fatal outcome in patients with severe pneumonia occurring more than 9 months after starting treatment with mogamulizumab.
As with all therapeutic proteins, there is a potential for immunogenicity. A small percentage of patients receiving POTELIGEO tested positive for treatment emergent (treatment induced or treatment boosted) anti mogamulizumab antibodies. There were no positive neutralising antibody responses.
Of the 320 subjects exposed to mogamulizumab in Study 0761-010, 21 (6.6%), experienced at least one serious adverse drug reaction (SADR) that occurred within 90 days from the date of last study drug administration.
Of these, SADRs that were reported in more than one patient were coded under the SOCs Infections and infestations (7 [2.2%] patients), General disorders and administration site conditions (5 [1.6%] patients), Respiratory, thoracic and mediastinal disorders (4 [1.3%] patients), Musculoskeletal and connective tissue disorders (3 [0.9%] patients), Hepatobiliary disorders (2 [0.6%] patients), and Injury, poisoning and procedural complications (2 [0.6%] patients). All remaining SOCs reported SADRs in one patient (0.3%).
The safety profile observed in the 90 days following the last dose of mogamulizumab is consistent with the safety profile observed during the study treatment period.
The safety profile in elderly patients (≥65 years) was generally consistent with that of adult patients, except for dermatologic reactions and infusion related reactions which were seen more often in older subjects.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. Mogamulizumab should not be infused concomitantly in the same intravenous line with other medicinal products.
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