MINJUVI Powder for concentrate for solution for infusion Ref.[50430] Active ingredients: Tafasitamab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infusion-related reactions

Infusion-related reactions may occur and have been reported more frequently during the first infusion (see section 4.8). Patients should be monitored closely throughout the infusion. Patients should be advised to contact their healthcare professionals if they experience signs and symptoms of infusion-related reactions including fever, chills, rash or breathing problems within 24 hours of infusion. A premedication should be administered to patients prior to starting tafasitamab infusion. Based on the severity of the infusion-related reaction, tafasitamab infusion should be interrupted or discontinued and appropriate medical management should be instituted (see section 4.2).

Myelosuppression

Treatment with tafasitamab can cause serious and/or severe myelosuppression including neutropenia, thrombocytopenia and anaemia (see section 4.8). Complete blood counts should be monitored throughout treatment and prior to administration of each treatment cycle. Based on the severity of the adverse reaction, tafasitamab infusion should be withheld (see Table 1). Refer to the lenalidomide SmPC for dosage modifications.

Neutropenia

Neutropenia, including febrile neutropenia, has been reported during treatment with tafasitamab. Administration of granulocyte colony-stimulating factors (G-CSF) should be considered, in particular in patients with Grade 3 or 4 neutropenia. Any symptoms or signs of developing infection should be anticipated, evaluated and treated.

Thrombocytopenia

Thrombocytopenia has been reported during treatment with tafasitamab. Withholding of concomitant medicinal products that may increase bleeding risk (e.g. platelet inhibitors, anticoagulants) should be considered. Patients should be advised to report signs or symptoms of bruising or bleeding immediately.

Infections

Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with tafasitamab. Tafasitamab should be administered to patients with an active infection only if the infection is treated appropriately and well controlled. Patients with a history of recurring or chronic infections may be at increased risk of infection and should be monitored appropriately. Patients should be advised to contact their healthcare professionals if fever or other evidence of potential infection, such as chills, cough or pain on urination, develops.

Tumour lysis syndrome

Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of tumour lysis syndrome. In patients with DLBCL, tumour lysis syndrome during treatment with tafasitamab has been observed. Appropriate measures/prophylaxis in accordance with local guidelines should be taken prior to treatment with tafasitamab. Patients should be monitored closely for tumour lysis syndrome during treatment with tafasitamab.

Immunisations

The safety of immunisation with live vaccines following tafasitamab therapy has not been investigated and vaccination with live vaccines is not recommended concurrently with tafasitamab therapy.

Excipient

This medicinal product contains 37.0 mg sodium per 5 vials (the dose of a patient weighing 83 kg), equivalent to 1.85% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

No interaction studies have been performed.

Treatment with tafasitamab in combination with lenalidomide should not be initiated in female patients unless pregnancy has been excluded. Please also refer to the SmPC of lenalidomide.

Women of childbearing potential / Contraception in females

Women of childbearing potential should be advised to use effective contraception during and for at least 3 months after end of treatment with tafasitamab.

Pregnancy

Reproductive and developmental toxicity studies have not been conducted with tafasitamab.

There are no data on the use of tafasitamab in pregnant women. However, IgG is known to cross the placenta and tafasitamab may cause foetal B-cell depletion based on the pharmacological properties (see section 5.1). In case of exposure during pregnancy, newborns should be monitored for B-cell depletion and vaccinations with live virus vaccines should be postponed until the infant’s B-cell count has recovered (see section 4.4).

Tafasitamab is not recommended during pregnancy and in women of childbearing potential not using contraception.

Lenalidomide can cause embryo-foetal harm and is contraindicated for use in pregnancy and in women of childbearing potential unless all of the conditions of the lenalidomide pregnancy prevention programme are met.

Breast-feeding

It is not known whether tafasitamab is excreted in human milk. However, maternal IgG is known to be excreted in human milk. There are no data on the use of tafasitamab in breast-feeding women and a risk for breast-feeding children cannot be excluded. Women should be advised not to breast-feed during and for at least 3 months after the last dose of tafasitamab.

Fertility

No specific studies have been conducted to evaluate potential effects of tafasitamab on fertility. No adverse effects on male and female reproductive organs were observed in a repeat-dose toxicity study in animals (see section 5.3).

MINJUVI has no or negligible influence on the ability to drive and use machines. However, fatigue has been reported in patients taking tafasitamab and this should be taken into account when driving or using machines.

Summary of the safety profile

The most common adverse reactions are: infections (73%), neutropenia (51%), asthenia (38%), anaemia (36%), diarrhoea (36%), thrombocytopenia (31%), cough (26%), oedema peripheral (24%), pyrexia (24%), decreased appetite (22%). The most common serious adverse reactions were infection (26%) including pneumonia (7%), and febrile neutropenia (6%).

Permanent discontinuation of tafasitamab due to an adverse reaction occurred in 15% of patients. The most common adverse reactions leading to permanent discontinuation of tafasitamab were infections and infestations (5%), nervous system disorders (2.5%), and respiratory, thoracic and mediastinal disorders (2.5%).

The frequency of dose modification or interruption due to adverse reactions was 65%. The most common adverse reactions leading to tafasitamab treatment interruption were blood and lymphatic system disorders (41%).

Tabulated list of adverse reactions

Adverse reactions reported in clinical trials are listed by MedDRA System Organ Class and by frequency. The frequencies of adverse reactions is based on the pivotal phase 2 trial MOR208C203 (L-MIND) with 81 patients. Patients were exposed to tafasitamab for a median of 7.7 months. The adverse reaction frequencies from clinical trials are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than the medicinal product, such as the disease, other medicines or unrelated causes.

Frequencies are defined as follows: 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); and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 2. Adverse reactions in patients with relapsed or refractory DLBCL who received tafasitamab in the clinical trial MOR208C203 (L-MIND):

⁺ Further information on this adverse reaction is provided in the text below. Compared with the incidences on combination therapy with lenalidomide, the incidences of non-haematological adverse reactions on tafasitamab monotherapy decreased by at least 10% for decreased appetite, asthenia, hypokalaemia, constipation, nausea, muscle spasms, dyspnoea and C-reactive protein increased.

Description of selected adverse reactions

Myelosuppression

Treatment with tafasitamab can cause serious or severe myelosuppression including neutropenia, thrombocytopenia and anaemia (see sections 4.2 and 4.4).

In the L-MIND study, myelosuppression (i.e. neutropenia, febrile neutropenia, thrombocytopenia, leukopenia, lymphopenia or anaemia) occurred in 65.4% of patients treated with tafasitamab. Myelosuppression was managed by reduction or interruption of lenalidomide, interruption of tafasitamab and/or administration of G-CSF (see sections 4.2 and 4.4). Myelosuppression led to interruption of tafasitamab in 41% and to tafasitamab discontinuation in 1.2%.

Neutropenia / febrile neutropenia

Incidence of neutropenia was 51%. Incidence of Grade 3 or 4 neutropenia was 49% and of Grade 3 or 4 febrile neutropenia was 12%. Median duration of any adverse reaction of neutropenia was 8 days (range 1-222 days); median time to onset to first occurrence of neutropenia was 49 days (range 1-994 days).

Thrombocytopenia

Incidence of thrombocytopenia was 31%. Incidence of Grade 3 or 4 thrombocytopenia was 17%. Median duration of any adverse reaction thrombocytopenia was 11 days (range 1-470 days); median time to onset to first occurrence of thrombocytopenia was 71 days (range 1-358 days).

Anaemia

Incidence of anaemia was 36%. Incidence of Grade 3 or 4 anaemia was 7%. Median duration of any adverse reaction of anaemia was 15 days (range 1-535 days); median time to onset to first occurrence of anaemia was 49 days (range 1-1129 days).

When patients in the L-MIND study were switched from tafasitamab and lenalidomide in the combination therapy phase to tafasitamab alone in the extended monotherapy phase, the incidences of haematological events decreased by at least 20% for neutropenia, thrombocytopenia and anaemia; no incidences of febrile neutropenia were reported with tafasitamab monotherapy (see sections 4.2 and 4.4).

Infections

In the L-MIND study, infections occurred in 73% of patients. Incidence of Grade 3 or 4 infections was 28%. The most frequently reported Grade 3 or higher infections were pneumonia (7%), respiratory tract infections (4.9%), urinary tract infections (4.9%) and sepsis (4.9%). Infection was fatal in <1% of patients (pneumonia) within 30 days of last treatment.

Median time to first onset of Grade 3 or 4 infection was 62.5 days (4-1014 days). Median duration of any infection was 11 days (1-392 days).

Recommendations for management of infections are provided in section 4.4. Infection led to dose interruption of tafasitamab in 27% and tafasitamab discontinuation in 4.9%.

Infusion-related reactions

In the L-MIND study, infusion-related reactions occurred in 6% of patients. All infusion related reactions were Grade 1 and resolved on the day of occurrence. Eighty percent of these reactions occurred during cycle 1 or 2. Symptoms included chills, flushing, dyspnoea and hypertension (see sections 4.2 and 4.4).

Immunogenicity

In 245 patients treated with tafasitamab, no treatment-emergent or treatment-boosted anti-tafasitamab antibodies were observed. Pre-existing anti-tafasitamab antibodies were detected in 17/245 patients (6.9%) with no impact on pharmacokinetics, efficacy or safety of tafasitamab.

Special populations

Elderly

Among 81 patients treated in the L-MIND study, 56 (69%) patients were >65 years of age. Patients >65 years of age had a numerically higher incidence of serious treatment emergent adverse events (TEAEs) (55%) than patients ≤65 years (44%).

Reporting of suspected adverse reactions

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.

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

No incompatibilities have been observed with standard infusion materials.