Leaflet MINJUVI 200mg powder for concentrate infusion solution

MINJUVI 200 mg powder for concentrate for solution for infusion

One vial of powder contains 200 mg of tafasitamab.

After reconstitution each mL of solution contains 40 mg of tafasitamab.

Tafasitamab is a humanised CD19-specific monoclonal antibody of the immunoglobulin G (IgG)subclass produced in mammalian (Chinese hamster ovary) cells by recombinant DNA technology.

Each vial of MINJUVI contains 7.4 mg of sodium and 1.0 mg of polysorbate 20. For the full list ofexcipients, see section 6.1.

Powder for concentrate for solution for infusion (powder for concentrate).

White to slightly yellowish lyophilised powder.

MINJUVI is indicated in combination with lenalidomide followed by MINJUVI monotherapy for thetreatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) whoare not eligible for autologous stem cell transplant (ASCT).

MINJUVI is indicated in combination with lenalidomide and rituximab for the treatment of adultpatients with relapsed or refractory follicular lymphoma (FL) (Grade 1-3a) after at least one line ofsystemic therapy.

MINJUVI must be administered by a healthcare professional experienced in treatment of cancerpatients.

Recommended premedication

A premedication to reduce the risk of infusion-related reactions should be administered 30 minutes to2 hours prior to tafasitamab infusion. For patients not experiencing infusion-related reactions duringthe first 3 infusions, premedication is optional for subsequent infusions.

The premedication may include antipyretics (e.g. paracetamol), histamine H1 receptor blockers (e.g.diphenhydramine), histamine H2 receptor blockers (e.g. cimetidine), and/or glucocorticosteroids (e.g.methylprednisolone).

Treatment of infusion-related reactions

If an infusion-related reaction occurs (Grade 2 and higher), the infusion should be interrupted. Inaddition, appropriate medical treatment of symptoms should be initiated. After signs and symptomsare resolved or reduced to Grade 1, MINJUVI infusion can be resumed at a reduced infusion speed(see Table 1).

If a patient has experienced a Grade 1 to 3 infusion-related reaction, premedication should beadministered before subsequent tafasitamab infusions.

Combination with lenalidomide

As MINJUVI is indicated in combination with lenalidomide, please refer to the lenalidomide

Summary of Product Characteristics (SmPC) for the recommendations on prophylactic antithromboticmedicines.

Recommended dose for the treatment of adult patients with relapsed or refractory DLBCL

The recommended dose of MINJUVI is 12 mg per kg body weight administered as an intravenousinfusion according to the following schedule:

* Cycle 1: infusion on day 1, 4, 8, 15 and 22 of the cycle.

* Cycles 2 and 3: infusion on day 1, 8, 15 and 22 of each cycle.

* Cycle 4 until disease progression: infusion on day 1 and 15 of each cycle.

Each cycle has 28 days.

In addition, patients should self-administer lenalidomide capsules at the recommended starting dose of25 mg daily on days 1 to 21 of each cycle. The starting dose and subsequent dosing may be adjustedaccording to the lenalidomide SmPC.

MINJUVI plus lenalidomide in combination is given for up to twelve cycles.

Treatment with lenalidomide should be stopped after a maximum of twelve cycles of combinationtherapy. Patients should continue to receive MINJUVI infusions as single agent on day 1 and 15 ofeach 28-day cycle, until disease progression or unacceptable toxicity.

Recommended dose for the treatment of adult patients with relapsed or refractory FL after at least oneline of systemic therapy

The recommended dose of MINJUVI is 12 mg per kg body weight administered as an intravenousinfusion according to the following schedule:

* Cycle 1 to 3: infusion on day 1, 8, 15 and 22 of each cycle.

* Cycles 4 to 12: infusion on day 1 and 15 of each cycle.

Each cycle has 28 days.

The recommended starting dose of rituximab is 375 mg/m2 administered as an intravenous infusionaccording to the following schedule:

* Cycle 1: on days 1, 8, 15 and 22.

* Cycles 2 to 5: on day 1 of each cycle.

Each cycle has 28 days. Please refer to the SmPC of rituximab intravenous formulations forinformation on its method of administration and premedication and prophylactic medications.

In addition, patients should self-administer lenalidomide capsules at the recommended starting dose of20 mg daily on days 1 to 21 of each 28-day cycle. The starting dose and subsequent dosing may beadjusted according to the lenalidomide SmPC.

MINJUVI in combination with lenalidomide plus rituximab is given for up to twelve cycles for

MINJUVI and lenalidomide, and five cycles for rituximab. Treatment with rituximab should bestopped after five cycles of combination therapy. Patients should continue to receive MINJUVIinfusions in combination with oral lenalidomide up to cycle twelve. Treatment with tafasitamab pluslenalidomide should be stopped after a maximum of twelve cycles.

Table 1 provides dose modifications for MINJUVI in case of adverse reactions. For dosemodifications regarding lenalidomide, please also refer to the lenalidomide SmPC.

Table 1: Dose modifications in case of adverse reactions

Adverse reaction Severity Dosage modification

Infusion-related * Interrupt MINJUVI infusionreactions immediately and manage signs andsymptoms.

* Once signs and symptoms resolve orreduce to Grade 1, resume MINJUVIinfusion at no more than 50% of the rate

Grade 2 (moderate) at which the reaction occurred. If thepatient does not experience furtherreaction within 1 hour and vital signsare stable, the infusion rate may beincreased every 30 minutes as toleratedto the rate at which the reactionoccurred.

* Interrupt MINJUVI infusionimmediately and manage signs andsymptoms.

* Once signs and symptoms resolve orreduce to Grade 1, resume MINJUVIinfusion at no more than 25% of the rate

Grade 3 (severe) at which the reaction occurred. If thepatient does not experience furtherreaction within 1 hour and vital signsare stable, the infusion rate may beincreased every 30 minutes as toleratedto a maximum of 50% of the rate atwhich the reaction occurred.

* If after rechallenge the reaction returns,stop the infusion immediately.

Grade 4 (life-threatening) * Stop the infusion immediately andpermanently discontinue MINJUVI.

Myelosuppression * Withhold MINJUVI and lenalidomideand monitor complete blood countweekly until platelet count is 50,000/µL

Platelet count of less than or higher.50,000/µL * Resume MINJUVI at the same dose andlenalidomide at a reduced dose ifplatelets return to ≥ 50,000/µL. Refer tothe lenalidomide SmPC for dosagemodifications.

Neutrophil count of less than * Withhold MINJUVI and lenalidomide1,000/µL for at least 7 days and monitor complete blood countweekly until neutrophil count isor 1,000/µL or higher.

* Resume MINJUVI at the same dose and

Neutrophil count of less than lenalidomide at a reduced dose if1,000/µL with an increase of neutrophils return to ≥ 1000/µL. Referbody temperature to 38 °C or to the lenalidomide SmPC for dosagehigher modifications.

Adverse reaction Severity Dosage modificationor

Neutrophil count lessthan 500/µL

The safety and efficacy of MINJUVI in children under 18 years have not been established.

No data are available.

No dose adjustment is needed for elderly patients (≥ 65 years).

No dose adjustment is needed for patients with mild or moderate renal impairment (see section 5.2).

There are no data in patients with severe renal impairment for dosing recommendations.

No dose adjustment is needed for patients with mild hepatic impairment (see section 5.2). There are nodata in patients with moderate or severe hepatic impairment for dosing recommendations.

MINJUVI is for intravenous use after reconstitution and dilution.

* For the first infusion of cycle 1, the intravenous infusion rate should be 70 mL/h for the first30 minutes. Afterwards, the rate should be increased to complete the first infusion within a2.5-hour period.

* All subsequent infusions should be administered within a 1.5 to 2-hour period.

* In case of adverse reactions, consider the recommended dose modifications provided in Table 1.

* MINJUVI must not be co-administered with other medicinal products through the same infusionline.

* MINJUVI must not be administered as an intravenous push or bolus.

For instructions on reconstitution and dilution of the medicinal product before administration, seesection 6.6.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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

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 beadvised to contact their healthcare professionals if they experience signs and symptoms ofinfusion-related reactions including fever, chills, rash or breathing problems within 24 hours ofinfusion. 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 ordiscontinued and appropriate medical management should be instituted (see section 4.2).

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

SmPC for dosage modifications.

Neutropenia, including febrile neutropenia, has been reported during treatment with tafasitamab.

Administration of granulocyte colony-stimulating factors (G-CSF) should be considered, in particularin patients with Grade 3 or 4 neutropenia. Any symptoms or signs of developing infection should beanticipated, evaluated and treated.

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

Fatal and serious infections, including opportunistic infections, occurred in patients during treatmentwith tafasitamab. Tafasitamab should be administered to patients with an active infection only if theinfection is treated appropriately and well controlled. Patients with a history of recurring or chronicinfections 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 ofpotential infection, such as chills, cough or pain on urination, develops.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has been reported during combination therapywith tafasitamab. Patients should be monitored for new or worsening neurological symptoms or signsthat may be suggestive of PML. The symptoms of PML are nonspecific and can vary depending on theaffected region of the brain. These include altered mental status, memory loss, speech impairment,motor deficits (hemiparesis or monoparesis), limb ataxia, gait ataxia, and visual symptoms such ashemianopia and diplopia. If PML is suspected, further dosing of tafasitamab must be immediatelysuspended. Referral to a neurologist should be considered. Appropriate diagnostic measures mayinclude MRI scan, cerebrospinal fluid testing for JC viral DNA and repeat neurological assessments. If

PML is confirmed, tafasitamab must be permanently discontinued.

Patients with high tumour burden and rapidly proliferative tumour may be at increased risk of tumourlysis syndrome. Tumour lysis syndrome has been reported during treatment with tafasitamab.

Appropriate measures/prophylaxis in accordance with local guidelines should be taken prior totreatment with tafasitamab. Patients should be monitored closely for tumour lysis syndrome duringtreatment with tafasitamab.

CD19-negative or CD20-negative disease

There are no data available on patients with CD19-negative or CD20-negative FL treated withtafasitamab in combination with lenalidomide and rituximab, and it is possible that patients with

CD19-negative or CD20-negative FL may have less benefit compared to patients with CD19-positiveand CD20-positive FL. The potential risks and benefits associated with treatment of patients with

CD19-negative or CD20-negative FL with tafasitamab in combination with lenalidomide andrituximab should be considered.

The safety of immunisation with live vaccines following tafasitamab therapy has not been investigatedand 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.

This medicinal product contains 5.0 mg of polysorbate 20 per 5 vials. Polysorbate 20 may causeallergic reactions.

No interaction studies have been performed.

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

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

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 theplacenta 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-celldepletion and vaccinations with live virus vaccines should be postponed until the infant’s B-cell counthas recovered (see section 4.4).

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

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

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

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

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

Patients with relapsed or refractory DLBCL

The safety of tafasitamab in patients with DLBCL was evaluated in the open-label, multicentre, single-arm phase 2 study L-MIND in 81 patients with relapsed or refractory DLBCL. Patients receivedtafasitamab 12 mg/kg intravenously in combination with lenalidomide for a maximum of 12 cycles,followed by tafasitamab monotherapy until disease progression or unacceptable toxicity.

The median duration of exposure to tafasitamab was 7.7 months.

The most common adverse reactions were: infections (73%), neutropenia (51%), asthenia (40%),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%), andfebrile neutropenia (6%).

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

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

Patients with relapsed or refractory FL after at least one line of systemic therapy

The safety of tafasitamab in patients with FL was evaluated in the randomised, double-blind, placebo-controlled multicenter phase 3 study inMIND in 652 patients, including 546 participants with relapsedor refractory (R/R) follicular lymphoma and 106 participants with R/R marginal zone lymphoma.

Patients received tafasitamab 12 mg/kg (n = 327) or placebo (n = 325) intravenously in combinationwith rituximab 375 mg/m2 intravenously (for a maximum of 5 cycles) and lenalidomide 20 mg orally(for a maximum of 12 cycles). Tafasitamab treatment was stopped after 12 cycles. Among patientswho received tafasitamab, 83% were exposed for 6 months or longer. The median duration ofexposure to tafasitamab was 322 days.

In the inMIND study, the most common adverse reactions were infections (68%), including viralinfections (41%) and bacterial infections (27%); neutropenia (57%), rash (36.4%), asthenia (34.9%),pyrexia (19%), thrombocytopenia (17%), anaemia (17%), infusion related reaction (15.9%), pruritus(15.6%) and headache (10.4%).

The most common serious adverse reactions were infections (26%), including viral infections (13%),and bacterial infections (6%); febrile neutropenia (2.8%), acute kidney injury (2.8%) and pyrexia(1.8%).

Permanent discontinuation of tafasitamab due to an adverse reaction occurred in 11.6% of patients.

The most common adverse reactions leading to permanent discontinuation of tafasitamab were viralinfections (2.4%), including COVID-19 (1.5%) and COVID-19 pneumonia (1.2%), infusion-relatedreaction (0.9%) and pyrexia (0.9%).

The frequency of tafasitamab dose modification or interruption due to adverse reactions was 74.9%.

The most common adverse reactions leading to tafasitamab dose modification and interruption wereneutropenia (38.8%) and viral infections (23.9%) including COVID-19 (21.1%) and COVID-19pneumonia (3.7%).

Adverse reactions reported for tafasitamab in clinical trials are listed by MedDRA System Organ Classand by frequency.

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 medicinalproduct, 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 theavailable data). Within each frequency grouping, adverse reactions are presented in order ofdecreasing seriousness.

Table 2: Adverse reactions in patients with relapsed or refractory DLBCL who receivedtafasitamab in combination with lenalidomide in the clinical trial MOR208C203(L-MIND)

System organ class Frequency Adverse reactions

Infections and infestations Very common Bacterial, viral and fungal infections+,including opportunistic infections with fataloutcomes (e.g. bronchopulmonaryaspergillosis, bronchitis, pneumonia andurinary tract infection)

Common Sepsis (including neutropenic sepsis)

Neoplasms benign, Common Basal cell carcinomamalignant and unspecified(incl. cysts and polyps)

Blood and lymphatic system Very common Febrile neutropenia+, neutropenia+,disorders thrombocytopenia+, anaemia, leukopenia+

Common Lymphopenia

Immune system disorders Common Hypogammaglobulinaemia

Metabolism and nutrition Very common Hypokalaemia, decreased appetitedisorders Common Hypocalcaemia, hypomagnesaemia

Nervous system disorders Common Headache, paraesthesia, dysgeusia

Respiratory, thoracic and Very common Dyspnoea, coughmediastinal disorders Common Exacerbation of chronic obstructive pulmonarydisease, nasal congestion

Gastrointestinal disorders Very common Diarrhoea, constipation, vomiting, nausea,abdominal pain

Hepatobiliary disorders Common Hyperbilirubinaemia, transaminases increased(includes ALT and/or AST increased),

Gamma-glutamyltransferase increased

Skin and subcutaneous Very common Rash (includes different types of rash, e.g. rash,tissue disorders rash maculopapular, rash pruritic, rasherythematous)

Common Pruritus, alopecia, erythema, hyperhidrosis

Musculoskeletal and Very common Back pain, muscle spasmsconnective tissue disorders Common Arthralgia, pain in extremity, musculoskeletalpain

Renal and urinary disorders Common Blood creatinine increased

General disorders and Very common Asthenia++ , oedema peripheral, pyrexiaadministration site Common Mucosal inflammationconditions

Investigations Common Weight decreased, C-reactive protein increased

Injury, poisoning and Common Infusion related reactionprocedural complications+Further information on this adverse reaction is provided in the text below.++ Asthenia includes asthenia, fatigue and malaise.

Compared with the incidences on combination therapy with lenalidomide, the incidences of non-haematological adversereactions on tafasitamab monotherapy decreased by at least 10% for decreased appetite, asthenia, hypokalaemia, constipation,nausea, muscle spasms, dyspnoea and C-reactive protein increased.

Table 3: Adverse reactions in patients with relapsed or refractory FL who received tafasitamabin combination with rituximab and lenalidomide in INCMOR 0208-301 (inMIND)

System organ class/Adverse All grades Grade 3-4areaction frequency frequency

Viral infectionsb Very common Very common

Bacterial infectionsc Very common Common

Pneumonia Very common Common

Bronchitis Common -

Sepsis Common Uncommon

Neutropeniad Very common Very common

Thrombocytopeniae Very common Common

Anaemiaf Very common Common

Febrile neutropenia Common Common

Leukopenia Common Uncommon

Tumour lysis syndrome Uncommon Uncommon

Headache Very common Uncommon

Diarrhoea Very common Uncommon

Constipation Very common Uncommon

Abdominal paing Very common -

Rashh Very common Common

Pruritus Very common Uncommon

Astheniai Very common Common

Pyrexia Very common Common

Chills Common -

ALT increased Common Uncommon

AST increased Common Uncommon

Injury, poisoning, and procedural complications

Infusionrelated reaction Very common Uncommona The severity of adverse drug reactions was assessed based on the CTCAE, defining grade 1 = mild, grade 2 =moderate, grade 3 = severe, grade 4=life threatening, and 5=death.b Includes viral infection, COVID-19, COVID-19 pneumonia, coronavirus infection, coronavirus test positive,cytomegalovirus chorioretinitis, cytomegalovirus infection reactivation, gastroenteritis rotavirus, genital herpes,

Hepatitis B, herpes ophthalmic, herpes simplex, herpes simplex reactivation, herpes virus infection, herpes zoster,herpes zoster reactivation, influenza, laryngitis viral, nasal herpes, norovirus infection, oral herpes, parainfluenzaevirus infection, pneumonia viral, progressive multifocal leukoencephalopathy, respiratory syncytial virus infection,respirovirus test positive, rhinovirus infection, skin papilloma, varicella zoster pneumonia, varicella zoster virusinfection, and viral upper respiratory tract infection.

c Includes bacterial infection, abdominal infection, abscess, appendicitis, asymptomatic bacteriuria, atypicalpneumonia, bacteraemia, bacterial sepsis, breast abscess, bronchopulmonary aspergillosis, campylobactergastroenteritis, campylobacter infection, carbuncle, catheter site infection, cellulitis, cholecystitis, chronic sinusitis,clostridium difficile colitis, clostridium difficile infection, corynebacterium infection, device related infection,diverticulitis, ear infection, ear lobe infection, empyema, enterobacter bacteraemia, erysipelas, erythrasma,escherichia infection, escherichia sepsis, eye infection, folliculitis, furuncle, hemophilus bacteraemia, hemophilusinfection, helicobacter gastritis, helicobacter infection, infected cyst, infected dermal cyst, lower respiratory tractinfection, moraxella infection, mycobacterium chelonae infection, myopericarditis, myringitis, otitis externa, otitismedia, perineal infection, periodontitis, peritonitis bacterial, pneumocystis jirovecii pneumonia, pneumoniamoraxella, pneumonia pneumococcal, pneumonia streptococcal, postoperative wound infection, proctitis, prostatitis,pseudomonal sepsis, pseudomonal skin infection, pseudomonas infection, pulmonary sepsis, pulpitis dental,pyelonephritis, salmonellosis, septic shock, sinusitis, skin infection, soft tissue infection, staphylococcal bacteraemia,staphylococcal infection, tooth abscess, tooth infection, urinary tract infection, urosepsis, vaginal infection, andwound infection.

d Includes neutropenia and neutrophil count decreased.e Includes thrombocytopenia and platelet count decreased.f Includes anaemia and haematocrit decreased.g Includes abdominal pain, abdominal discomfort, abdominal pain lower, abdominal pain upper, and gastrointestinalpain.h Includes rash, rash erythematous, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular, andurticaria.i Includes asthenia, malaise, and fatigue.

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 led to interruption of tafasitamab in 41% and to tafasitamab discontinuation in1.2%.

In the inMIND study, myelosuppression (i.e. neutropenia, febrile neutropenia, thrombocytopenia,leukopenia, lymphopenia or anaemia) occurred in 63.3% of patients treated with tafasitamab,lenalidomide, and rituximab (tafasitamab group) and 63.1% of patients treated with lenalidomide andrituximab (placebo group). Grade 4 haematological adverse reactions included neutropenia,thrombocytopenia and febrile neutropenia. Myelosuppression led to interruption of tafasitamab in42.8% and to tafasitamab discontinuation in 1.5%.

Myelosuppression was managed by reduction or interruption of lenalidomide, interruption oftafasitamab and/or rituximab. In addition, severe neutropenia was managed by the administration of

GCSF (see sections 4.2 and 4.4).

Neutropenia/febrile neutropenia

In the L-MIND study, incidence of neutropenia was 51%. Incidence of Grade 3 or 4 neutropenia was49% and of Grade 3 or 4 febrile neutropenia was 12%. Median duration of any adverse reaction ofneutropenia was 8 days (range 1 - 222 days); median time to onset to first occurrence of neutropeniawas 49 days (range 1 - 994 days).

In the inMIND study, incidence of neutropenia was 56.9% in the tafasitamab group (tafasitamab,lenalidomide and rituximab) and 54.2% in the placebo group (lenalidomide and rituximab). Incidenceof Grade 3 or 4 neutropenia was 46.8% in the tafasitamab group and 45.5% in the placebo group.

Incidence of Grade 3 or Grade 4 febrile neutropenia was 4.3% in the tafasitamab group and 3.4% inthe placebo group. Median duration of any adverse reaction of neutropenia was 11 days (range 1 - 433days). Median duration of febrile neutropenia was 5 days (range 1 - 57 days); median time to onset tofirst occurrence of neutropenia was 57 days (range 1 - 338 days); median time to onset to firstoccurrence of febrile neutropenia was 77 days (range 3 - 304 days).

In the L-MIND study, incidence of thrombocytopenia was 31%. Incidence of Grade 3 or 4thrombocytopenia 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 (range1 - 358 days).

In the inMIND study, incidence of thrombocytopenia was 17.1% in the tafasitamab group(tafasitamab, lenalidomide and rituximab) and 20.6% in the placebo group (lenalidomide andrituximab). Incidence of Grade 3 or Grade 4 thrombocytopenia was 6.4% in the tafasitamab group and9.8% in the placebo group. Median duration of thrombocytopenia was 16 days (range 2 - 434 days);median time to onset to first occurrence of thrombocytopenia was 33 days (range 1 - 324 days).

In the L-MIND study, 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 toonset 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 thecombination therapy phase to tafasitamab alone in the extended monotherapy phase, the incidences ofhaematological events decreased by at least 20% for neutropenia, thrombocytopenia and anaemia; noincidences of febrile neutropenia were reported with tafasitamab monotherapy (see sections 4.2 and4.4).

In the inMIND study, incidence of anaemia was 17.1% in the tafasitamab group (tafasitamab,lenalidomide and rituximab) and 14.5% in the placebo group (lenalidomide and rituximab). Incidenceof Grade 3 or 4 anaemia was 6.4% in the tafasitamab group and 6.5% in the placebo group. Medianduration of any adverse reaction of anaemia was 23 days (range 1 - 432 days); median time to onset tofirst occurrence of anaemia was 49 days (range 1 - 274 days).

In the L-MIND study, infections occurred in 73% of patients. Incidence of Grade 3 or 4 infections was28%. The most frequently reported Grade 3 or higher infections were pneumonia (7%), respiratorytract 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 ofany infection was 11 days (1 - 392 days).

Infection led to dose interruption of tafasitamab in 27% and tafasitamab discontinuation in 4.9%.

In the inMIND study, infections occurred in 52.3% of patients in the tafasitamab group (tafasitamab,lenalidomide and rituximab) and in 45.2% of patients in the placebo group (lenalidomide andrituximab). Viral infections occurred in 41.3% of patients in the tafasitamab group and 32% in theplacebo group. Bacterial infections occurred in 27.2% of patients in the tafasitamab group and 25.2%in the placebo group. Incidence of Grade 3 or 4 viral infections was 11.6% in the tafasitamab groupand 4.6% in the placebo group. Incidence of Grade 3 or 4 bacterial infections was 7.6% in thetafasitamab group and 7.7% in the placebo group. Infections were fatal in 3 patients in the tafasitamabgroup (two cases of COVID-19 and one of sepsis).

Median time to first onset of any infection ≥ Grade 3 was 10 days (2 - 311 days).

Recommendations for management of infections are provided in section 4.4.

In the L-MIND study, infusion-related reactions occurred in 6% of patients. All infusion relatedreactions were Grade 1 and resolved on the day of occurrence. Eighty percent of these reactionsoccurred during cycle 1 or 2.

In study inMIND, infusion-related reactions occurred in 15.9% of patients in the tafasitamab group(tafasitamab, lenalidomide and rituximab) and 15.1% in the placebo group (lenalidomide andrituximab). Grade 3 infusion-related reactions occurred in 6.1% of patients in the tafasitamab group. Inthe tafasitamab group infusion-related reactions occurred in 15.3% of patients during cycle 1, in 1.3%of patients during cycle 2 and in 0.3% of patients during cycle 3.

Symptoms included chills, flushing, dyspnoea, hypertension and rash (see sections 4.2 and 4.4).

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

Anti-drug antibodies (ADAs) were tested in 327 patients with relapsed or refractory follicularlymphoma or relapsed or refractory marginal zone lymphoma who received tafasitamab in studyinMIND. The incidence of tafasitamab treatment-emergent ADAs was 0.9% (3/327) using a bridgingenzyme-linked immunosorbent assay.

No neutralizing antibodies were detected. There was no apparent clinically meaningful effect of ADAson the pharmacokinetics, pharmacodynamics, safety, or effectiveness of tafasitamab over the mediantreatment duration of 322.5 days.

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%).

Among the 274 patients with FL treated with tafasitamab in study inMIND, 50% were ≥ 65 years of ageand 20% were ≥ 75 years of age. No clinically meaningful differences in safety or effectiveness wereobserved between these patients and younger patients but greater sensitivity of some older individualscannot be ruled out.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

In the case of an overdose, patients should be carefully observed for signs or symptoms of adversereactions and supportive care should be administered, as appropriate.

Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01FX12.

Tafasitamab is an Fc-enhanced monoclonal antibody that targets the CD19 antigen expressed on thesurface of pre-B and mature B lymphocytes.

Upon binding to CD19, tafasitamab mediates B-cell lysis through:

* engagement of immune effector cells like natural killer cells, γδ T cells and phagocytes

* direct induction of cell death (apoptosis)

The Fc modification results in enhanced antibody-dependent cellular cytotoxicity andantibody-dependent cellular phagocytosis.

Tafasitamab induced a rapid reduction in peripheral blood B-cell counts. In patients with relapsed orrefractory DLBCL, the reduction relative to baseline B-cell count reached 97% after eight days oftreatment in the L-MIND study. The maximum B-cell reduction at approximately 100% (median) wasreached within 16 weeks of treatment.

In patients with relapsed or refractory follicular lymphoma, circulating B-cells decreased toundetectable levels by day 8 following administration of the recommended dosage of tafasitamab inpatients who had detectable B-cells at treatment initiation. The depletion was sustained while patientsremained on treatment.

Although the depletion of B-cells in the peripheral blood is a measurable pharmacodynamic effect, itis not directly correlated with the depletion of B-cells in solid organs or in malignant deposits.

Relapsed or refractory DLBCL

Tafasitamab plus lenalidomide followed by tafasitamab monotherapy was studied in the L-MINDstudy, an open-label multicentre single-arm study. This study was conducted in adult patients withrelapsed or refractory DLBCL after 1 to 3 prior systemic DLBCL therapies, who at the time of the trialwere not candidates for high dose chemotherapy followed by ASCT or who had refused ASCT. Oneof the prior systemic therapies had to include a CD20 targeted therapy. The study excluded patientswith severe hepatic impairment (total serum bilirubin > 3 mg/dL) and patients with renal impairment(CrCL< 60 mL/min.), as well as patients with history or evidence of clinically significantcardiovascular, CNS and/or other systemic disease. Patients with a known history of“double/triple-hit” genetics DLBCL were also excluded at study entry.

For the first three cycles, patients received 12 mg/kg tafasitamab via infusion on day 1, 8, 15 and 22 ofeach 28-day cycle, plus a loading dose on day 4 of cycle 1. Thereafter, tafasitamab was administeredon days 1 and 15 of each cycle until disease progression. Premedication including antipyretics,histamine H1 and H2 receptor blockers and glucocorticosteroids was given 30 to 120 minutes prior tothe first three tafasitamab infusions.

Patients self-administered 25 mg lenalidomide daily on days 1 to 21 of each 28-day cycle, up to12 cycles.

A total of 81 patients were enrolled in the L-MIND study. The median age was 72 years (range 41 to86 years), 89% were white and 54% were males. Out of 81 patients, 74 (91.4%) had ECOGperformance score of 0 or 1 and 7 (8.6%) had ECOG score of 2. The median number of prior therapieswas two (range: 1 to 4), with 40 patients (49.4%) receiving one prior therapy and 35 patients (43.2%)receiving 2 prior lines of treatment. Five patients (6.2%) had 3 prior lines of therapies and 1 (1.2%)had 4 prior lines of treatment. All patients had received a prior anti-CD20-containing therapy. Eightpatients had a diagnosis of DLBCL transformed from low-grade lymphoma. Fifteen patients (18.5%)had primary refractory disease, 36 (44.4%) were refractory to their last prior therapy, and 34 (42.0%)were refractory to rituximab. Nine patients (11.1%) had received prior ASCT. The primary reasons forpatients not being candidates for ASCT included age (45.7%), refractory to salvage chemotherapy(23.5%), comorbidities (13.6%) and refusal of high dose chemotherapy/ASCT (16.0%).

One patient received tafasitamab, but not lenalidomide. The remaining 80 patients received at least onedose of tafasitamab and lenalidomide. All patients enrolled in the L-MIND study had a diagnosis of

DLBCL based on local pathology. However, as per central pathology review, 10 patients could not beclassified as DLBCL.

The median duration of exposure to treatment was 9.2 months (range: 0.23, 54.67 months). Thirty-two(39.5%) patients completed 12 cycles of tafasitamab. Thirty (37.0%) patients completed 12 cycles oflenalidomide.

The primary efficacy endpoint was best objective response rate (ORR), defined as the proportion ofcomplete and partial responders, as assessed by an independent review committee (IRC). Otherefficacy endpoints included duration of response (DoR), progression-free survival (PFS) and overallsurvival (OS). The efficacy results are summarised in Table 4.

Table 4: Efficacy results in patients with relapsed or refractory diffuse large B-cell lymphomain the MOR208C203 (L-MIND) study

Efficacy parameter Tafasitamab + lenalidomide(N = 81 [ITT]*)30-NOV-2019 cut-off 30-OCT-2020 cut-off(24 months analysis) (35 months analysis)

Primary endpoint

Best objective response rate (per IRC)

Overall response rate, n (%) 46 (56.8) 46 (56.8)(95% CI) [45.3, 67.8] [45.3, 67.8]

Complete response rate, n 32 (39.5) 32 (39.5)(%) [28.8, 51.0] [28.8, 51.0](95% CI)

Partial response rate, n (%) 14 (17.3) 14 (17.3)(95% CI) [ 9.8, 27.3] [ 9.8, 27.3]

Secondary endpoint

Overall duration of response (complete + partial response) a

Median, months 34.6 43.9(95% CI) [26.1, NR] [26.1, NR]

ITT = intention to treat; NR = not reached

*One patient received only tafasitamab

CI: Binomial exact confidence interval using Clopper Pearson methoda Kaplan Meier estimates

Overall survival (OS) was a secondary endpoint in the study. After a median follow up time of42.7 months (95% CI: 38.0; 47.2), the median OS was 31.6 months (95% CI: 18.3; not reached).

Amongst the eight patients who had a DLBCL transformed from a prior indolent lymphoma, sevenpatients had an objective response (three patients a CR, four patients a PR) and one patient had astable disease as the best response to tafasitamab+ lenalidomide treatment.

Relapsed or refractory FL after at least one line of systemic therapy

The efficacy of tafasitamab in combination with lenalidomide and rituximab in patients with relapsedor refractory follicular lymphoma was evaluated in a randomised, double-blind, placebo-controlledphase 3 study (inMIND; INCMOR 0028-301).

Eligible patients were adults aged 18 years and above with histologically confirmed grade 1-3afollicular lymphoma (WHO 2016) whose disease relapsed or became refractory after at least 1 priorline of systemic therapy, including an anti-CD20 therapy. In addition, GELF criteria wererecommended as guidance to the investigators, to identify the FL patients that were in need oftreatment. As per inclusion criteria, all patients included in the study were required to havedocumented CD20+ and CD19+ expression based on local or central pathology review. The studyexcluded patients with CNS involvement or prior allogeneic HSCT.

A total of 548 patients with R/R follicular lymphoma were randomized in a 1:1 ratio to receivetafasitamab plus lenalidomide and rituximab or placebo plus R2 for up to twelve 28-day cycles.

Randomization was stratified by progression of disease within 24 months after initial diagnosis(POD24) (yes vs no), refractoriness to prior CD20-directed antibody therapy (yes vs no), and thenumber of prior lines of therapy (< 2 vs ≥ 2).

Dosing in each treatment arm was as follows:

* Tafasitamab 12 mg/kg intravenously (Days 1, 8, 15 and 22 of Cycles 1 to 3 and on Days 1 and15 of Cycles 4 to 12) and lenalidomide 20 mg orally once daily (Days 1 to 21 of Cycles 1 to12) with rituximab 375 mg/m² intravenously (Days 1, 8, 15 and 22 of Cycle 1 and on Day 1 of

Cycles 2 to 5).

* Placebo intravenously (Days 1, 8, 15, and 22 of Cycles 1 to 3 and on Days 1 and 15 of Cycles 4 to 12)and lenalidomide 20 mg orally once daily (Days 1 to 21 of Cycles 1 to 12) with rituximab 375 mg/m²intravenously (Days 1, 8, 15, and 22 of Cycle 1 and on Day 1 of Cycles 2 to 5).

The baseline demographics and disease characteristics were generally well balanced between the twotreatment groups. Among the 548 patients with R/R FL enrolled in study inMIND, the median age was64 years (range 31 to 88 years), 54.6% were male, and 79.9% were White. The median time sinceinitial diagnosis was 5.3 years (range 0 to 34 years). Most participants (56.8%) had Ann Arbor Stage

IV disease at study entry. Approximately half of participants had high-risk disease as per FLIPI score,and most participants met at least one GELF criterion for high tumour burden. Most participants had

ECOG performance status of 0 (66.4%) and 37.8% of participants had a bulky disease (> 7cm).

The majority (54.7%) of participants had received 1 prior systemic anticancer line of therapy; themedian number of prior therapies was 1 (range: 1 to 10), 209 patients (38.1%) were refractory to theirlast prior therapy. All participants in the FL Population had received prior anti-CD20 therapy; mostparticipants had received 1 (61.3%) or 2 (24.8%) prior anti-CD20 therapies. Two participants, both inthe placebo arm, received prior anti-CD 19 containing therapy. Prior treatments included R-CHOP(23.9% of participants), R-CHOP +R-maintenance (27.9% of participants), R-bendamustine (21.7% ofparticipants), rituximab monotherapy (17.2% of participants), R-bendamustine +R-maintenance(12.2% of participants), R-CVP (6.8% of participants), and R-CVP +R-maintenance (5.8% ofparticipants). Twenty-eight (5.1%) participants had received prior ASCT.

One third (34.3%) of participants were anti-CD20 refractory, and 31.6% had progression of diseasewithin 24 months of initial diagnosis (POD24).

A total of 546 participants (99.6%) with R/R FL were treated, including 273 participants (100.0%) inthe tafasitamab+R2 group and 273 participants (99.3%) in the placebo+R2 group.

The primary efficacy endpoint was investigator-assessed progression-free survival (PFS) in the FLpopulation, defined as the time from randomization to first documented disease progression, or deathfrom any cause, whichever occurs first. The key secondary endpoints included PET-CR rate by INV inthe FDG-avid FL population, defined as a complete metabolic response at any time after start oftreatment, as well as overall survival in the FL population. The median duration of PFS follow-up was14.3 months (95% CI: 11.8, 15) in the tafasitamab group and 14.1 months (95% CI: 11.5, 15) in theplacebo group.

The efficacy results are summarized in Table 5 and Figure 1.

Table 5: Efficacy Results from Study INCMOR 0208-301 (inMIND)

Tafasitamab with Placebo with

Lenalidomide plus Lenalidomide plus

Endpoint Rituximab Rituximab(N = 273) (N = 275)

Progression-free survivala, b

Patients with event, n (%) 75 (27.5) 131 (47.6)

Median PFS (months) 22.4 13.9(95% CI)c (19.2, NE) (11.5, 16.4)

Hazard ratiod (95% CI) 0.43 (0.32, 0.58)p-value < 0.0001

Participants with FDG-avid PET Scan (N = 251) (N = 254)at Baselinea

PET-CR rate (95% CI)e, f 49.4 (43.1, 55.8) 39.8 (33.7, 46.1)

Odds ratio (95% CI) 1.5 (1.04, 2.13)p-value 0.0286

CI = confidence interval; NE = not evaluable.a Investigator-assessedb Per Cheson 2014 Response Criteriac Two-sided 95% CIs based on Brookmeyer and Crowley method.d Hazard ratio based on a stratified Cox proportional hazard model.e The PET-CR rate was defined as the proportion of patients in the FDG-avid FL population who achieved acomplete metabolic response at any time after the start of treatment as per Lugano classification among thepatients with a positive PET scan at baseline. Patients with no postbaseline assessment by PET or who didnot achieve a CMR were classified as non-CR responders.

f 95% CIs based on the Clopper-Pearson method.

Figure 1: Kaplan-Meier Curve for Progression-Free Survival by Investigator Assessment ininMIND1.0 Treatment Group0.9 Tafasitamab+Rituximab+Lenalidomide

Placebo+Rituximab+Lenalidomide0.80.70.60.50.4

Tafasitamab+Rituximab+Lenalidomide0.3

Placebo+Rituximab+Lenalidomide0.20.10.0 Censored0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Time to Events (Months)

Number of Patients at Risk

Tafasitamab+Rituximab+Lenalidomide 273 261 250 212 200 164 119 103 71 57 30 22 12 3 2 0

Placebo+Rituximab+Lenalidomide 275 265 235 192 173 126 82 70 48 40 26 16 10 2 2 0

At the interim analysis, the key secondary endpoint of OS was immature, and median OS was notreached in either treatment group (stratified hazard ratio of 0.587 (95% CI: 0.306, 1.128); p-value0.1061).

In the ITT set of L-MIND study, 36 of 81 patients were ≤ 70 years and 45 of 81 patients were> 70 years.

Among the 273 patients with R/R follicular lymphoma treated with tafasitamab in inMIND study, 178were ≤ 70 years and 95 were > 70 years.

No overall differences in efficacy were observed for patients ≤ 70 years versus patients > 70 years ofage.

The European Medicines Agency has waived the obligation to submit the results of studies with

MINJUVI in all subsets of the paediatric population in mature B-cell neoplasms (see section 4.2 forinformation on paediatric use).

This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. Thismeans that further evidence on this medicinal product is awaited.

The European Medicines Agency will review new information on this medicinal product at least everyyear and this SmPC will be updated as necessary.

The absorption, distribution, biotransformation and elimination were documented based on apopulation pharmacokinetic analysis.

Tafasitamab average serum trough concentrations (± standard deviation) were 178.4 (± 66) μg/mLduring weekly intravenous administrations of 12 mg/kg from cycle 1 to 3. During administration every14 days from cycle 4 to 6, average trough serum concentrations were 163.2 (± 74.3) μg/mL. Meanmaximum tafasitamab serum concentrations were 488.4 (± 126.6) μg/mL.

The total volume of distribution at steady state for tafasitamab was 7.11 L.

PPrroobbaabbiilliittyy ooff PPrrooggrreessssiioonn--FFrreeee SSuurrvviivvaall

The exact pathway through which tafasitamab is metabolised has not been characterised. As a human

IgG monoclonal antibody, tafasitamab is expected to be degraded into small peptides and amino acidsvia catabolic pathways in the same manner as endogenous IgG.

The clearance of tafasitamab was 0.44 L/day and terminal elimination half-life was 13.4 days.

Following long-term observations, tafasitamab clearance was found to decrease over time to0.29 L/day after two years.

Age, body weight, sex, tumour size, disease type, B-cell or absolute lymphocyte counts, anti-drugantibodies, lactate dehydrogenase and serum albumin levels had no relevant effect on thepharmacokinetics of tafasitamab. The influence of race and ethnicity on the pharmacokinetics oftafasitamab is unknown.

The effect of renal impairment was not formally tested in dedicated clinical trials; however, noclinically meaningful differences in the pharmacokinetics of tafasitamab were observed for mild tosevere renal impairment (creatinine clearance (CrCL) ≥ 15 and < 90 mL/min estimated by the

Cockcroft-Gault equation). The effect of end-stage renal disease (CrCL < 15 mL/min) is unknown.

The effect of hepatic impairment was not formally tested in dedicated clinical trials; however noclinically meaningful differences in the pharmacokinetics of tafasitamab were observed for mild tomoderate hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartateaminotransferase (AST) > ULN, or total bilirubin 1 to 3 times ULN and any AST). The effect ofmoderate to severe hepatic impairment (total bilirubin > 3 times ULN and any AST) is unknown.

Preclinical data reveal no special hazards for humans.

Repeat dose toxicology studies

Tafasitamab has shown to be highly specific to the CD19 antigen on B cells. Toxicity studiesfollowing intravenous administration to cynomolgus monkeys have shown no other effect than theexpected pharmacological depletion of B-cells in peripheral blood and in lymphoid tissues. Thesechanges reversed after cessation of treatment.

Mutagenicity/carcinogenicity

As tafasitamab is a monoclonal antibody, genotoxicity and carcinogenicity studies have not beenconducted, since such tests are not relevant for this molecule in the proposed indication.

Reproductive and developmental toxicity studies as well as specific studies to evaluate the effects onfertility have not been conducted with tafasitamab. However, no adverse effects on reproductiveorgans in males and females and no effects on menstrual cycle length in females were observed in the13-week repeat-dose toxicity study in cynomolgus monkeys.

Sodium citrate dihydrate

Citric acid monohydrate

Trehalose dihydrate

Polysorbate 20

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

No incompatibilities have been observed with standard infusion materials.

Unopened vial5 years

Reconstituted solution (prior to dilution)

Chemical and physical in-use stability has been demonstrated for up to 30 days at 2 °C - 8 °C or up to24 hours at 25 °C.

From a microbiological point of view, the reconstituted solution should be used immediately. If notused immediately, in-use storage times and conditions are the responsibility of the user and wouldnormally not be longer than 24 hours at 2 - 8 °C, unless reconstitution has taken place in controlledand validated aseptic conditions. Do not freeze or shake.

Diluted solution (for infusion)

Chemical and physical in-use stability has been demonstrated for a maximum of 14 days at 2 °C -8 °C followed by up to 24 hours at up to 25 °C.

From a microbiological point of view, the diluted solution should be used immediately. If not usedimmediately, in-use storage times and conditions prior to use are the responsibility of the user andwould normally not be longer than 24 hours at 2 - 8 °C, unless dilution has taken place in controlledand validated aseptic conditions. Do not freeze or shake.

Store in a refrigerator (2 °C - 8 °C).

Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

Clear type I glass vial with a butyl rubber stopper, aluminium seal and a plastic flip-off cap containing200 mg tafasitamab. Pack size of one vial.

MINJUVI is provided in sterile, preservative-free single-use vials.

MINJUVI should be reconstituted and diluted prior to intravenous infusion.

Use appropriate aseptic technique for reconstitution and dilution.

* Determine the dose of tafasitamab based on patient weight by multiplying 12 mg by the patientweight (kg). Then calculate the number of tafasitamab vials needed (each vial contains 200 mgtafasitamab) (see section 4.2).

* Using a sterile syringe, gently add 5.0 mL sterile water for injections into each MINJUVI vial.

Direct the stream toward the walls of each vial and not directly on the lyophilised powder.

* Gently swirl the reconstituted vial(s) to aid the dissolution of the lyophilised powder. Do notshake or swirl vigorously. Do not remove the contents until all of the solids have beencompletely dissolved. The lyophilised powder should dissolve within 5 minutes.

* The reconstituted solution should appear as a colourless to slightly yellow solution. Beforeproceeding, ensure there is no particulate matter or discolouration by inspecting visually. If thesolution is cloudy, discoloured or contains visible particles, discard the vial(s).

* An infusion bag containing 250 mL sodium chloride 9 mg/mL (0.9%) solution for injectionshould be used.

* Calculate the total volume of the 40 mg/mL reconstituted tafasitamab solution needed.

Withdraw a volume equal to this from the infusion bag and discard the withdrawn volume.

* Withdraw the total calculated volume (mL) of reconstituted tafasitamab solution from the vial(s)and slowly add to the sodium chloride 9 mg/mL (0.9%) infusion bag. Discard any unusedportion of tafasitamab remaining in the vial.

* The final concentration of the diluted solution should be between 2 mg/mL to 8 mg/mL oftafasitamab.

* Gently mix the intravenous bag by slowly inverting the bag. Do not shake.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Incyte Biosciences Distribution B.V.

Paasheuvelweg 251105 BP Amsterdam

Netherlands

EU/1/21/1570/001

Date of first authorisation: 26 August 2021

Date of latest renewal: 17 September 2025

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.