PRODUCT MONOGRAPH
INCLUDING PATIENT MEDICATION INFORMATIONMINJUVI™
Tafasitamab for injection
lyophilized powder for solution for infusion (200 mg single-use vial)
Professed Standard
Antineoplastic, monoclonal antibody
ATC code: L01FX12
PR

Minjuvi, indicated in combination with lenalidomide for the treatment of adult patients with relapsed
or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arisingfrom low grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT), has been
issued marketing authorization with conditions, pending the results of trials to verify its clinicalbenefit. Patients should be advised of the nature of the authorization. For further information for
Minjuvi, please refer to Health Canada’s Notice of Compliance with conditions - drug products web
site: https://www.canada.ca/en/health-canada/services/drugs-health-products/drugproducts/notice-compliance/conditions.html

Incyte Corporation
1801 Augustine Cut-Off
Wilmington, DE 19803
USA
www.incyte.com

Date of Initial
Authorization:
August 19, 2021

Imported by:
Innomar Strategies
Oakville, ON
L6L 0C4
Submission Control Number: 247025

MINJUVI™ (tafasitamab)

Page 1 of 30

What is a Notice of Compliance with Conditions (NOC/c)?
An NOC/c is a form of market approval granted to a product on the basis of promising evidence of clinicaleffectiveness following review of the submission by Health Canada.
Products authorized under Health Canada’s NOC/c policy are intended for the treatment, prevention or
diagnosis of a serious, life-threatening or severely debilitating illness. They have demonstrated promising
benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment.
In addition, they either respond to a serious unmet medical need in Canada or have demonstrated asignificant improvement in the benefit/risk profile over existing therapies. Health Canada has provided
access to this product on the condition that sponsors carry out additional clinical trials to verify the
anticipated benefit within an agreed upon time frame
TABLE OF CONTENTSTABLE OF CONTENTS ............................................................................................................... 2
PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 4
1
1.1
1.2

INDICATIONS .......................................................................................................... 4
Pediatrics ................................................................................................................... 4
Geriatrics ................................................................................................................... 4

2

CONTRAINDICATIONS ............................................................................................. 4

3

SERIOUS WARNINGS AND PRECAUTIONS BOX........................................................ 5

4
4.1
4.2
4.3
4.4

DOSAGE AND ADMINISTRATION ............................................................................ 5
Dosing Considerations .............................................................................................. 5
Recommended Dose and Dosage Adjustment ........................................................ 6
Reconstitution ........................................................................................................... 8
Administration .......................................................................................................... 95

OVERDOSAGE ....................................................................................................... 10

6

DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .......................... 10

7
7.1
7.1.1
7.1.2
7.1.3
7.1.4

WARNINGS AND PRECAUTIONS............................................................................ 11
Special Populations ................................................................................................. 13
Pregnant Women ................................................................................................. 13
Breast-feeding ...................................................................................................... 13
Pediatrics (< 18 years of age) ............................................................................... 13
Geriatrics (≥ 65 years of age) ............................................................................... 14

8
8.1
8.2
8.3

ADVERSE REACTIONS............................................................................................ 14
Adverse Reactions Overview .................................................................................. 14
Clinical Trial Adverse Reactions .............................................................................. 14
Less Common Clinical Trial Adverse Reactions ...................................................... 16

MINJUVI™ (tafasitamab)

Page 2 of 30

8.4

Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other
Quantitative Data.................................................................................................... 17

9
9.2
9.3
9.4
9.5
9.6
9.7

DRUG INTERACTIONS ........................................................................................... 17
Drug Interactions Overview .................................................................................... 17
Drug-Behavioral Interactions.................................................................................. 17
Drug-Drug Interactions ........................................................................................... 18
Drug-Food Interactions ........................................................................................... 18
Drug-Herb Interactions ........................................................................................... 18
Drug-Laboratory Test Interactions ......................................................................... 18

10
10.1
10.2
10.3

CLINICAL PHARMACOLOGY ................................................................................... 18
Mechanism of Action .............................................................................................. 18
Pharmacodynamics ................................................................................................. 18
Pharmacokinetics .................................................................................................... 18

11

STORAGE, STABILITY AND DISPOSAL .................................................................... 19

13

PHARMACEUTICAL INFORMATION ....................................................................... 21

14
14.1
14.2

CLINICAL TRIALS ................................................................................................... 21
Trial Design and Study Demographics .................................................................... 21
Study Results ........................................................................................................... 22

15

MICROBIOLOGY .................................................................................................... 23

16

NON-CLINICAL TOXICOLOGY ................................................................................. 23

17

SUPPORTING PRODUCT MONOGRAPHS ............................................................... 23

PATIENT MEDICATION INFORMATION ................................................................................... 24

MINJUVI™ (tafasitamab)

Page 3 of 30

Minjuvi, indicated in combination with lenalidomide for the treatment of adult patients with relapsed
or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arisingfrom low grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT), has been
issued marketing authorization with conditions, pending the results of trials to verify its clinical benefit.
Patients should be advised of the nature of the authorization. For further information for Minjuvi,
please refer to Health Canada’s Notice of Compliance with conditions - drug products website.

PART I: HEALTH PROFESSIONAL INFORMATION
1

INDICATIONS

Minjuvi (tafasitamab for injection) is indicated in combination with lenalidomide for the treatment of
adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified,including DLBCL arising from low grade lymphoma, who are not eligible for autologous stem celltransplant (ASCT).
Authorization was based on overall response rate, complete response rate and durability of response
from a single-arm clinical study. An improvement in progression-free survival or overall survival has notbeen established (see Section 14 CLINICAL TRIALS).
1.1

Pediatrics

Pediatrics (< 18 years of age): No data are available to Health Canada; therefore, Health Canada has not
authorized an indication for pediatric use.
1.2

Geriatrics

Geriatrics (≥ 65 years of age): Among 81 patients treated in the L-MIND study, 72% were 65 years andolder. Patients 65 years of age and older had more serious treatment emergent adverse events (TEAEs)(57%) than younger patients (39%) (see Section 4.2 DOSAGE AND ADMINISTRATION, Recommended
Dose and Dosage Adjustment, Dose Modifications for Special Populations, and Section 10.3 CLINICALPHARMACOLOGY, Pharmacokinetics).
Evidence from clinical studies does not suggest that use in the geriatric population is associated withdifferences in effectiveness.
2

CONTRAINDICATIONS

Minjuvi (tafasitamab) is contraindicated in patients who are hypersensitive to this drug or to any
ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, (see Section 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

MINJUVI™ (tafasitamab)

Page 4 of 30

3

SERIOUS WARNINGS AND PRECAUTIONS BOX

Serious Warnings and Precautions
•

•

•

•

Infection - Clinically significant and/or life-threatening adverse events including fatal, life
threatening, or serious infections, including opportunistic infections have been reported in patientstreated with Minjuvi in combination with lenalidomide (see Section 7 WARNINGS AND
PRECAUTIONS).
Myelosuppression - Serious and severe myelosuppression, including neutropenia, febrileneutropenia, thrombocytopenia and anemia have been reported in patients treated with Minjuvi in
combination with lenalidomide (see Section 7 WARNINGS AND PRECAUTIONS).
Progressive Multifocal Leukoencephalopathy - PML can occur in patients receiving Minjuvi in
combination with lenalidomide. Minjuvi treatment should be interrupted in case of PML suspicion,
until the diagnosis can be clearly established. Discontinue Minjuvi therapy and consider
discontinuation or reduction of lenalidomide therapy in patients who develop PML (see Section 7
WARNINGS AND PRECAUTIONS).
Hepatitis B Virus (HBV) Reactivation – HBV reactivation has been observed in studies of Minjuvi in
combination with lenalidomide. Patients should be screened for HBV infection before treatment
initiation, and should be monitored during and after treatment with Minjuvi. In the event of HBVreactivation, Minjuvi should be discontinued (see Section 7 WARNINGS AND PRECAUTIONS).

4

DOSAGE AND ADMINISTRATION

4.1

Dosing Considerations

Minjuvi must be administered by a healthcare professional experienced in the treatment of cancer
patients who has immediate access to emergency equipment and appropriate medical support tomanage infusion-related reactions (IRRs) (see Section 7 WARNINGS AND PRECAUTIONS).
Minjuvi is administered by intravenous infusion only. DO NOT administer as an IV push or bolus dose.
Recommended Premedication
Administer premedication 30 minutes to 2 hours prior to Minjuvi infusion to reduce the risk of infusionrelated reactions (see Section 7 WARNINGS AND PRECAUTIONS). Premedication may include
antipyretics, histamine H1 receptor antagonists, histamine H2 receptor antagonists, and/or
glucocorticosteroids. For patients who do not experience an infusion-related reaction during the first 3
infusions, premedication is optional for subsequent infusions.
Treatment of infusion-related reactions
If an infusion-related reaction occurs (grade 2 or higher), interrupt the infusion. In addition, initiate
appropriate medical treatment of symptoms (see Table 1: Dose Modifications in Case of Adverse
Reactions). See Table 1 for guidance on when to resume Minjuvi infusion.
If a patient has a Grade 1 to 3 infusion-related reaction, premedication should be administered before
every subsequent Minjuvi infusion. See Table 1 for guidance on when to permanently discontinue
Minjuvi.

MINJUVI™ (tafasitamab)

Page 5 of 30

4.2

Recommended Dose and Dosage Adjustment

The recommended dose is 12 mg Minjuvi per kilogram body weight administered as an intravenous
infusion according to the following schedule:•

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

•

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

•

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

Each treatment cycle is 28 days long.
Minjuvi is to be administered with lenalidomide for up to 12 cycles. Patients should self-administerlenalidomide capsules at the recommended starting dose of 25 mg daily on days 1 to 21 of each cycle.
The starting dose and subsequent dosing should be adjusted, as necessary, according to thelenalidomide product monograph.
After a maximum of twelve cycles of combination therapy, stop treatment with lenalidomide andcontinue to administer Minjuvi infusions on day 1 and 15 of each 28-day cycle, until disease progression
or unacceptable toxicity.
Pediatrics
Health Canada has not authorized an indication for pediatric use.
Dose Modifications
Temporary interruption or definitive discontinuation of Minjuvi treatment may be required for infusionrelated reactions (IRRs) or myelosuppression (see Table 1 for guidance).
Recommended Dose Modification for lenalidomide used in combination with Minjuvi: Refer to the
manufacturer’s Product Monograph for the co-administered product, lenalidomide, for toxicity
management, dose adjustment guidelines for special populations, and contraindications (see Section 17
SUPPORTING PRODUCT MONOGRAPHS).
Table 1:

Dose modifications in case of adverse reactions

Adverse Reaction
Infusion-related
reactions

MINJUVI™ (tafasitamab)

Severity
Grade 2 (moderate)••

Minjuvi Dose Modification
Interrupt infusion immediately and manage
signs and symptoms.
Once signs and symptoms resolve or
reduce to Grade 1, resume infusion at no
more than 50% of the rate at which thereaction occurred. If the patient does notexperience further reaction within 1 hourand vital signs are stable, the infusion rate
may be increased every 30 minutes as
tolerated to rate at which the reaction
occurred.

Page 6 of 30

Adverse Reaction

Severity
Grade 3 (severe)

Minjuvi Dose Modification• Interrupt infusion immediately and manage
signs and symptoms.
• Once signs and symptoms resolve or
reduce to Grade 1, resume infusion at no
more than 25% of the rate at which thereaction occurred. If the patient does notexperience further reaction within 1 hourand vital signs are stable, the infusion rate
may be increased every 30 minutes as
tolerated to a maximum of 50% of the rate
at which the reaction occurred.
• If after rechallenge the reaction returns,
stop the infusion immediately.
Grade 4
• Stop the infusion immediately, manage(life-threatening)
signs and symptoms, and permanently
discontinue Minjuvi.
Myelosuppression
Thrombocytopenia:• Withhold Minjuvi and lenalidomide andPlatelet count of lessmonitor complete blood count (CBC)than 50,000/mcL
weekly until platelet count is 50,000/mcL
or higher.
• When platelet count recovers to at least
50,000/mcL, resume Minjuvi at the same
dose and lenalidomide at a reduced dose.
Refer to the lenalidomide productmonograph for additional guidance on
dosage modifications.
Neutropenia:• Withhold Minjuvi and lenalidomide andNeutrophil count of lessmonitor CBC weekly until neutrophil countthan 1,000/mcL for at
is 1,000/ mcL or higher.
least 7 days OR• When neutrophil count recovers to at least
Neutrophil count of
1,000/mcL, resume Minjuvi at the same
1,000/mcL or less withdose and lenalidomide at a reduced dose.
an increase of body
Refer to lenalidomide product monographtemperature to 38°C orfor dosage modifications. Refer to thehigher OR
lenalidomide product monograph for
Neutrophil count lessadditional guidance on dosage
than 500/mcL
modifications.
Abbreviations: mcL – microliters, CBC – complete blood countDose Modifications for Special Populations
Pediatric use: The safety and effectiveness of Minjuvi have not been established in pediatric patients
under 18 years of age. Health Canada has not authorized an indication for pediatric use (see Section 1.1
INDICATIONS, Pediatrics).
Geriatric patients: No dose adjustment is needed for elderly patients ≥ 65 years (see Section 10.3
CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions, Geriatrics).

MINJUVI™ (tafasitamab)

Page 7 of 30

Renal impairment: No dose adjustment of Minjuvi is required in patients with mild or moderate renal
impairment. The effect of renal impairment was not formally tested in dedicated clinical trials; however,no clinically meaningful differences in the pharmacokinetics of tafasitamab were observed for mild tomoderate renal impairment (CrCL ≥ 30 and < 90 mL/min estimated by the Cockcroft-Gault equation).
The effect of severe renal impairment to end-stage renal disease (CrCL < 30 mL/min) is unknown(see Section 10.3 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations and Conditions,
Renal Insufficiency).
Hepatic impairment: No dose adjustment of Minjuvi is required in patients with mild hepatic
impairment. The effect of hepatic impairment was not formally tested in dedicated clinical trials;
however, no clinically meaningful differences in the pharmacokinetics of tafasitamab were observed for
mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and
any AST). The effect of moderate to severe hepatic impairment (total bilirubin > 1.5 times ULN and anyAST) is unknown (see Section 10.3 CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations
and Conditions, Hepatic Insufficiency).
4.3

Reconstitution

Table 2:

Reconstitution

Vial Size(mg/vial)

Volume of Diluent to be
Added to Vial

Approximate
Available Volume

Concentration per mL

200 mg

5 mL sterile water for
injection

5 mL

40 mg/mL

Minjuvi is provided in sterile, preservative free single-use vials. Minjuvi should be reconstituted anddiluted prior to intravenous infusion. Use appropriate aseptic technique for reconstitution and dilution.
1. Determine the dose of Minjuvi based on patient weight (measured prior to each cycle) bymultiplying 12 mg/kg by the patient weight (kg).
2. Calculate the number of Minjuvi vials needed (each vial contains 200 mg tafasitamab).
3. Using a sterile syringe, gently add 5 mL sterile water for injection into each tafasitamab vial.
Direct the stream toward the walls of each vial and not directly on the lyophilized powder. The
resulting solution contains Minjuvi at a concentration of 40 mg/mL.
4. Gently swirl the reconstituted vial(s) to aid the dissolution of the lyophilized powder. Do notshake or swirl vigorously. Do not remove the contents until all of the solids have been
completely dissolved. The lyophilized powder should completely dissolve within 5 minutes.
5. The reconstituted Minjuvi solution should appear as a colourless to slightly yellow solution.
Before proceeding, ensure there is no particulate matter or discolouration by visually inspecting
the vials. If the solution is cloudy, discoloured or contains visible particles, discard the vial(s) andprepare freshly reconstituted Minjuvi.
6. The reconstituted Minjuvi solution contains no preservative and should be used as soon as
possible after reconstitution. If not used immediately, the reconstituted product may be stored

MINJUVI™ (tafasitamab)

Page 8 of 30

prior to dilution for up to 24 hours at 2°C – 25°C. Do not freeze or shake. Protect from lightduring storage.
Dilution
1. Obtain an infusion bag containing 250 mL sodium chloride 9 mg/mL (0.9%) solution for
injection.
2. Calculate the total volume of the 40 mg/mL reconstituted Minjuvi solution needed based on
the patient’s weight prior to each cycle.
𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉 =𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀𝑀 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 (12𝑚𝑚𝑚𝑚⁄𝑘𝑘𝑘𝑘) × 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑡𝑡 ′ 𝑠𝑠 𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤ℎ𝑡𝑡 (𝑘𝑘𝑘𝑘)
𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅 𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 (40 𝑚𝑚𝑚𝑚/𝑚𝑚𝑚𝑚)

3. Withdraw saline solution equal to the calculated volume from the infusion bag and discard thewithdrawn volume.
4. Withdraw the total calculated volume (mL) of reconstituted Minjuvi solution from the vial(s)and slowly add to the sodium chloride 9 mg/mL (0.9%) infusion bag. Discard any unused
portion of tafasitamab remaining in the vial.
5. The final concentration of the diluted solution should be between 2 mg/mL to 8 mg/mL oftafasitamab. Gently mix the intravenous bag by inverting the bag slowly. Do not shake.
6. Once diluted, the product should be used immediately. If not used immediately, the infusion
solution may be stored for a maximum of 36 hours at 2°C - 8°C followed by up to 24 hours at up
to 25°C. Do not freeze or shake. Protect from light during storage.
Any unused medicinal product or waste material should be disposed of in accordance with local
requirements (see Section 11 STORAGE, STABILITY and DISPOSAL).
Incompatibilities
No incompatibilities have been observed between Minjuvi infusion solutions with standard infusionmaterials.
4.4

Administration

Do not administer Minjuvi as an intravenous push or bolus.
Recommended supplies: 250 mL 0.9% NaCl infusion bag or bottle; standard IV infusion
administration set, and 0.2 µm in-line filter. No incompatibilities have been observed between
Minjuvi with infusion containers made of polypropylene (PP), polyvinylchloride (PVC),
polyethylene (PE), polyethylenterephthalate (PET), or glass and infusion sets made ofpolyurethane (PUR) or PVC. No incompatibilities were observed with terminal in-line filters withneutral or positively charged polyethersulfone (PES) membrane, 0.2 µm.
•

Administer Minjuvi as an intravenous infusion after reconstitution and dilution.

•

For the first infusion of cycle 1, the intravenous infusion rate should be 70 mL/h for the first
30 minutes. Afterwards, increase the rate so that the first infusion is complete within a 2.5-hour
period.

MINJUVI™ (tafasitamab)

Page 9 of 30

•Monitor patients during the entire infusion for infusion-related reactions. Most infusion-related
reactions occur in the first 15 minutes of the first dose. Follow standard care measures formonitoring after the infusion is complete. Advise patients to contact their healthcare professional
if they experience signs and symptoms of infusion-related reactions including fever, chills, rash or
breathing problems within 24 hours of infusion.

•

In the absence of any prior infusion-related reaction, subsequent infusions may be administered
within a 1.5 - 2-hour period.

•

Do not co-administer other medicines through the same infusion line.

•

After the infusion is complete, flush the tubing with 0.9% NaCl injection to ensure the entire doseis administered.

5

OVERDOSAGE

There is no information on overdose with Minjuvi. The recommended dose of Minjuvi is 12 mg/kg, whichis the highest dose that has been tested in clinical studies. In the case of an overdose, patients should be
carefully observed for signs or symptoms of adverse reactions and supportive care should be
administered, as appropriate.
For management of a suspected drug overdose, contact your regional poison control centre.
6

DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING

Table 3:

Dosage Forms, Strengths, Composition and Packaging

Route of
Administration
Intravenous Infusion

Dosage Form /Strength/Composition
lyophilized powder,
200 mgNon-medicinal Ingredients
citric acid monohydrate, polysorbate 20,
sodium citrate dihydrate, and trehalose
dihydrate

Minjuvi for injection: 200 mg of tafasitamab as white to slightly yellowish lyophilized powder insingle-dose vial for reconstitution and further dilution.
Packaging: Minjuvi (tafasitamab) is supplied as a vial containing 200 mg per vial with an outer carton.

MINJUVI™ (tafasitamab)

Page 10 of 30

7

WARNINGS AND PRECAUTIONSGeneralInfusion-related reactions
Infusion-related reactions may occur and have been reported in clinical studies with Minjuvi. Infusionrelated reactions may occur more frequently during the first infusion, but can occur during or after any
infusion. Patients should be monitored closely throughout the infusion. Advise patients to contact theirhealthcare professionals if they experience signs and symptoms of infusion-related reactions including
fever, chills, rash or breathing problems within 24 hours of infusion (see Section 8.2 ADVERSE
REACTIONS, Clinical Trial Adverse Reactions).
Premedicate patients prior to starting tafasitamab infusion. Monitor patients frequently during infusion.
If infusion reaction occurs or is suspected, immediately interrupt or discontinue Minjuvi based on theseverity of the infusion-related reaction. Institute appropriate medical management (see Section 4.1
DOSAGE AND ADMINISTRATION, Dosing Considerations).
Endocrine and Metabolism
Tumor Lysis Syndrome
Patients with high tumor burden and rapidly proliferative tumor may be at increased risk of tumor lysis
syndrome. In patients with R/R-DLBCL who received Minjuvi in clinical studies, tumor lysis syndrome has
been observed. Measures/prophylaxis appropriate for TLS should be instituted in accordance with local
guidelines prior to treatment with Minjuvi. Patients should be monitored closely for tumor lysis
syndrome during treatment with tafasitamab.
Hematology
Myelosuppression
Treatment with Minjuvi can cause serious and/or severe myelosuppression including neutropenia,
thrombocytopenia, and anemia. Monitor complete blood counts throughout treatment and prior toadministration of each treatment cycle. Withhold Minjuvi based on the severity of the adverse reaction(see Section 4.2 DOSAGE AND ADMINISTRATION, Recommended Dose and Dosage Adjustment, andSection 8.2 ADVERSE REACTIONS, Clinical Trial Adverse Reactions). Minjuvi is given in combination withlenalidomide, which may also cause myelosuppression, refer to the lenalidomide product monographfor guidance on lenalidomide related toxicity management.
Neutropenia
Neutropenia, including febrile neutropenia, has been reported during treatment with tafasitamab.
Administration of granulocyte colony-stimulating factors (G-CSF) may be considered. Anticipate,evaluate and treat any symptoms or signs of developing infection.
Thrombocytopenia
Thrombocytopenia has been reported during treatment with tafasitamab. Consider withholding
concomitant medications that may increase bleeding risk (e.g. platelet inhibitors, anticoagulants).
Advise patients to report signs or symptoms of bruising or bleeding immediately.

MINJUVI™ (tafasitamab)

Page 11 of 30

ImmuneImmunizations
The safety of immunization with live vaccines following Minjuvi therapy has not been investigated, andvaccination with live vaccines is not recommended concurrently with Minjuvi therapy.
Infections
Serious and/or fatal bacterial, fungal and new or reactivated viral infections, including opportunistic
infections, can occur in patients treated with Minjuvi.
Patients with a history of recurring or chronic infections may be at increased risk of infection and should
be monitored appropriately (see Section 8.2 ADVERSE REACTIONS, Clinical Trial Adverse Reactions).
Advise patients to contact their healthcare professionals if fever or other evidence of potential infection
such as chills, cough or pain on urination develops.
Hepatitis B Virus (HBV) Reactivation
Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure anddeath, can occur in patients treated with monoclonal antibodies that target B-lymphocytes. Reactivationof HBV replication is often followed by hepatitis, i.e., increase in transaminase levels and, in severecases, increase in bilirubin levels, liver failure, and death. Screen all patients for HBV infection bymeasuring HBsAg and anti-HBc before initiating treatment with Minjuvi.
Patients with active hepatitis B disease should not be treated with Minjuvi. Patients with positive
hepatitis B serology (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc
positive), should consult physicians with expertise in managing hepatitis B regarding monitoring andconsideration for HBV antiviral therapy.
Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs ofhepatitis or HBV reactivation during and for several months following treatment with Minjuvi. HBVreactivation has been reported for other B-cell cytolytic antibodies following completion of therapy. In
patients who develop reactivation of HBV while receiving Minjuvi, immediately discontinue Minjuvi andany concomitant anti-neoplastic therapy, and institute appropriate treatment. Resumption of Minjuvi inpatients whose HBV reactivation resolves should be discussed with physicians with expertise inmanaging hepatitis B.
Progressive Multifocal Leukoencephalopathy (PML)PML has been observed in clinical studies of Minjuvi. The diagnosis of PML should be considered in any
patient presenting with new-onset or changes to pre-existing neurologic manifestations. The symptomsof PML are non-specific and can vary. Common symptoms include muscular weakness, paralysis, sensory
abnormalities, cerebellar symptoms, and visual field defects. Evaluation of PML includes consultation
with a neurologist, brain magnetic resonance imaging (MRI), and lumbar puncture (CSF testing for JC
viral DNA). Therapy with Minjuvi should be withheld during the investigation of potential PML.
Discontinue Minjuvi therapy and consider discontinuation or reduction of any concomitant antineoplastic treatment or immunosuppressive therapy in patients who develop PML.

MINJUVI™ (tafasitamab)

Page 12 of 30

Reproductive Health: Female and Male Potential
Treatment with tafasitamab in combination with lenalidomide should not be initiated in female patients
unless pregnancy has been excluded. Please also refer to the product monograph for lenalidomide.
Fertility
No specific studies have been conducted to evaluate the potential effects of Minjuvi on fertility.
However, no adverse effects on male and female reproductive organs were observed in repeat dose
toxicity study in animals.
Teratogenicity
Based on its mechanism of action, Minjuvi may cause fetal B-cell depletion when administered to apregnant woman. Minjuvi in combination with lenalidomide should not be initiated in female patients
unless pregnancy has been excluded (see Section 7.1.1 WARNINGS AND PRECAUTIONS, Special
Populations, Pregnant Women).
Minjuvi may cause fetal harm. Advise females of reproductive potential to use effective contraception
during Minjuvi treatment and for at least 3 months after the end of treatment.
Lenalidomide has been found to be teratogenic. Please refer to the lenalidomide product monograph.
7.1

Special Populations

7.1.1

Pregnant Women

There are no data on the use of Minjuvi in pregnant women. However, IgG is known to cross theplacenta and Minjuvi may cause fetal B-cell depletion based on the mechanism of action (see Section
10.1 CLINICAL PHARMACOLOGY, Mechanism of Action).
Minjuvi is not recommended during pregnancy and in women of childbearing potential not using
contraception. Advise patients to notify their doctor if they become pregnant or intend to become
pregnant during Minjuvi therapy, as it may cause harm to the unborn baby.
Minjuvi is administered in combination with lenalidomide for up to 12 cycles. Lenalidomide can cause
embryo-fetal harm and is contraindicated for use in pregnancy and in women of childbearing potential
unless all of the conditions of the lenalidomide pregnancy prevention program are met.
7.1.2

Breast-feeding

It is not known whether tafasitamab is excreted in human milk. However, maternal IgG is known to be
excreted in human milk. Because of the potential for adverse reactions in nursing infants fromtafasitamab, advise women not to breast-feed during treatment with Minjuvi until at least 3 months
after the last dose.
7.1.3

Pediatrics (< 18 years of age)

No data are available to Health Canada; therefore, Health Canada has not authorized an indication for
pediatric use.

MINJUVI™ (tafasitamab)

Page 13 of 30

7.1.4

Geriatrics (≥ 65 years of age)

Among 81 patients treated in the L-MIND study, 72% were 65 years and older. No overall differences in
efficacy were observed in patients above 70 years of age or younger (see Section 1.2 INDICATIONS,
Geriatrics).
8

ADVERSE REACTIONS

8.1

Adverse Reactions Overview

In the clinical development program of Minjuvi, 427 patients have received Minjuvi, either as
monotherapy or in combination with other treatments. Of these, 35 patients with relapsed or refractory
DLBCL were treated with Minjuvi monotherapy (MOR208C201 study) and 80 patients with relapsed or
refractory DLBCL were treated with Minjuvi in combination with lenalidomide (MOR208C203 [L-MIND]
study).
8.2

Clinical Trial Adverse Reactions

Clinical trials are conducted under very specific conditions, the adverse reaction rates observed in theclinical trials may not reflect the rates observed in practice and should not be compared to the rates in
the clinical trials of another drug. Adverse reaction information from clinical trials may be useful for
identifying and approximating rates of adverse drug-reactions in real-world use.
The safety of Minjuvi has been evaluated in 81 patients with non-transplant eligible relapsed or
refractory DLBCL in the MOR208C203 (L-MIND) study in which Minjuvi was used in combination withlenalidomide. One patient received tafasitamab, but not lenalidomide. The remaining 80 patients
received at least one dose of tafasitamab and lenalidomide.
Serious adverse events occurred in 52% of patients who received tafasitamab. Serious adverse events in≥6% of patients included infections (26%) including pneumonia (7%), and febrile neutropenia (6%). Fatal
adverse events occurred in 5% of patients who received tafasitamab, including cerebrovascular accident(1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%) and sudden death(1.2%).
Permanent discontinuation of tafasitamab or lenalidomide due to an adverse event occurred in 25% of
patients and permanent discontinuation of tafasitamab due to an adverse event occurred in 15%. The
most frequent adverse event which resulted in permanent discontinuation of tafasitamab were
infections (5%), nervous system disorders (2.5%), respiratory, thoracic and mediastinal disorders (2.5%).
The adverse reactions from L-MIND are presented in Table 4.

MINJUVI™ (tafasitamab)

Page 14 of 30

Table 4:

Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Diffuse Large B-Cell
Lymphoma Who Received Minjuvi in L-MIND

Adverse Reaction
Blood and lymphatic system disorders
Neutropenia
AnemiaThrombocytopenia
Leukopenia
Febrile neutropenia
General disorders and administration site conditions
Asthenia1
Pyrexia
Peripheral edema
Gastrointestinal disorders
Diarrhea
Constipation
NauseaVomiting
Respiratory, thoracic and mediastinal disorders
Cough
Dyspnea
Infections
Respiratory tract infection2
Urinary tract infection3
Metabolism and nutrition disorders
Decreased appetite
Hypokalemia
Musculoskeletal and connective tissue disorders
Back pain
Muscle spasms
Skin and subcutaneous tissue disorders
Rash4

Minjuvi(N=81)All Grades
Grade 3 or 4
n (%)
n (%)
41 (51)29 (36)25 (31)
12 (15)10 (12)40 (49)6 (7)14 (17)9 (11)
10 (12)32 (39.5)(19) 24
19 (24)3 (3.7)(1) 1.2
029 (36)14 (17)12 (15)12 (15)

1 (1.2)00
0

21 (26)10 (12)

1 (1.2)
1 (1.2)43 (53.1)
14 (17)11 (13.6)
4 (4.9)18 (22)15 (19)05 (6)15 (19)12 (15)2 (2.5)0

13 (16)2 (2.5)

1

Includes fatigue and malaise

2

Respiratory tract infection includes bronchitis, bronchopulmonary aspergillosis, influenza, lower respiratory tract infection,nasopharyngitis, parainfluenzae virus infection, pharyngitis, pharyngitis streptococcal, pneumonia, respiratory syncytial virus
infection, respiratory tract infection, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, upper respiratory tract
infection bacterial, viral pharyngitis

3

Urinary tract infection includes: urinary tract infection, Escherichia urinary tract infection, urinary tract infection bacterial,and urinary tract infection enterococcal

MINJUVI™ (tafasitamab)

Page 15 of 30

4Rash includes rash, rash maculopapular, rash pruritus, rash erythematous

Description of selected adverse reactions
Myelosuppression
Treatment with Minjuvi can cause serious or severe myelosuppression including neutropenia,
thrombocytopenia and anaemia (see Section 4.2 DOSAGE AND ADMINISTRATION, Recommended Doseand Dosage Adjustment, and Section 7 WARNINGS AND PRECAUTIONS, Hematology). In patients treatedwith Minjuvi and lenalidomide, Grade 3 or higher hematological adverse reactions (in 59% of patients)
included neutropenia (49%), thrombocytopenia (17%), febrile neutropenia (12%), leukopenia andanemia (7%). Grade 4 hematological adverse reactions (in 31% of patients) included neutropenia(including agranulocytosis), thrombocytopenia, febrile neutropenia, and leukopenia.
When patients in MOR208C203 (L-MIND) were switched from tafasitamab and lenalidomide in the
combination therapy phase to tafasitamab alone in the extended monotherapy phase, the incidences ofhematological events decreased by at least 20% for neutropenia, anaemia and thrombocytopenia; no
incidences of febrile neutropenia were reported with tafasitamab monotherapy.
Infections
Bacterial, fungal, and new or reactivation of viral infections can occur during and following Minjuvi
therapy (see Section 7 WARNINGS AND PRECAUTIONS, Immune). Grade 3 or higher infections occurredin 30% of patients treated with Minjuvi and lenalidomide. The most frequently reported Grade 3 orhigher infections were pneumonia (7%), respiratory tract infections (4.9%), urinary tract infection (4.9%)
and sepsis (4.9%). Infection-related death was reported in 1% of patients (pneumonia) within 30 days oflast treatment.
Infusion-related reactions
In the MOR208C203 (L-MIND) study, 6% of patients experienced an infusion-related reaction; Eighty
percent of these reactions occurred during cycle 1 or 2; all were Grade 1 and resolved on the day ofoccurrence. Symptoms included chills, flushing, dyspnea and hypertension.
8.3

Less Common Clinical Trial Adverse Reactions

Blood and lymphatic system disorders: lymphopenia (6.2%)
General disorders and administration site conditions: infusion-related reaction (6.2%)
Infections: sepsis, including Klebsiella sepsis, neutropenic sepsis and streptococcal sepsis (4.9%)
Investigations: weight decreased (4.9%)
Musculoskeletal and connective tissue disorders: arthralgia (8.6%), pain in extremity (8.6%),
musculoskeletal pain (1.2%)
Neoplasms benign, malignant, and unspecified: basal cell carcinoma (1.2%)
Nervous system disorders: headache (9%), paresthesia (7%), dysgeusia (6%)

MINJUVI™ (tafasitamab)

Page 16 of 30

Respiratory, thoracic and mediastinal disorders: nasal congestion (4.9%), exacerbation of chronic
obstructive pulmonary disease (1.2%)
Skin and subcutaneous tissue disorders: pruritus (9.9%), erythema (3.7%), alopecia (2.5%), hyperhidrosis(2.5%)
8.4

Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data

Table 5:

Select Laboratory Abnormalities (>20%) Worsening from Baseline in Patients with
Relapsed or Refractory Diffuse Large B-Cell Lymphoma Who Received Minjuvi in L-MIND
Minjuvi1

Laboratory Abnormality

All Gradesn (%)

Grade 3 or 4n (%)

Chemistry
Glucose increased
36 (49)4 (5)Calcium decreased
35 (47)
1 (1.4)Gamma glutamyl transferase increased
25 (34)4 (5)Albumin decreased
19 (26)0Magnesium decreased
16 (22)0
Urate increased
15 (20)5 (7)Phosphate decreased
15 (20)4 (5)Creatinine increased
15 (20)1 (1.4)
Aspartate aminotransferase increased
15 (20)0Coagulation
Activated partial thromboplastin time increased
34 (46)3 (4.1)
1
The denominator used to calculate the rate was 74 based on the number of patients with a baseline
value and at least one post-treatment value.
9

DRUG INTERACTIONS

9.2

Drug Interactions Overview

No formal drug-drug interaction studies have been performed. In a population-pharmacokinetic
analysis, concomitant administration of lenalidomide had no clinically meaningful effect on Minjuvi
pharmacokinetics.
9.3

Drug-Behavioral Interactions

Women of child-bearing potential should use contraception while undergoing treatment with Minjuvi andfor at least 3 months after end of treatment. (see Section 7.1 WARNINGS AND PRECAUTIONS, Special
Populations).

MINJUVI™ (tafasitamab)

Page 17 of 30

9.4

Drug-Drug Interactions

Interactions with other drugs have not been established.
9.5

Drug-Food Interactions

Minjuvi can be administered with or without food (see Section 10.3 CLINICAL PHARMACOLOGY,
Pharmacokinetics).
9.6

Drug-Herb Interactions

Drug-herb interactions have not been studied
9.7

Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.
10

CLINICAL PHARMACOLOGY

10.1 Mechanism of Action
Tafasitamab is an Fc-enhanced monoclonal antibody that targets the CD19 antigen expressed on thesurface of pre-B and mature B lymphocytes and on several B-cell malignancies, including diffuse large Bcell lymphoma.
Upon binding to CD19, tafasitamab mediates B-cell lysis through apoptosis and immune effector
mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellularphagocytosis (ADCP). In in vitro laboratory studies conducted in DLBCL tumour cell lines, tafasitamab, in
combination with lenalidomide, was associated with greater cytotoxicity than observed when cells weretreated with either agent alone.
10.2

Pharmacodynamics

In patients with relapsed or refractory DLBCL, tafasitamab led to a reduction in peripheral blood B-cellcounts. The reduction relative to baseline B-cell count reached 97% after eight days of treatment in the
MOR208C203 (L-MIND) study. The maximum B-cell reduction at approximately 100% (median) was
reached within 16 weeks of treatment.
Although the depletion of B-cells in the peripheral blood is a measurable pharmacodynamic effect, it is
not directly correlated with the depletion of B-cells in solid organs or in malignant deposits.
10.3

Pharmacokinetics

Absorption: Based on a population pharmacokinetic analysis of Minjuvi in combination withlenalidomide, tafasitamab average serum trough concentrations (± standard deviation) were 179 (± 53)μg/mL during weekly intravenous administrations of 12 mg/kg (plus an additional dose on day 4 of cycle1). During administration every 14 days from cycle 4 to cycle 23 onwards, average trough serum

MINJUVI™ (tafasitamab)

Page 18 of 30

concentrations were 153 (± 68) μg/mL. Overall, maximum Minjuvi serum concentrations were
483 (± 109) μg/mL.
Distribution: The total volume of distribution for tafasitamab was 9.3 L (95% CI 8.59, 10.0 L).
Metabolism: 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 andamino acids via catabolic pathways in the same manner as endogenous IgG.
Elimination: The clearance of tafasitamab was 0.41 L/day and terminal elimination half-life was
16.9 days (95% CI 15.4, 18.4 days). Following long-term observations, tafasitamab clearance was foundto decrease over time to 0.19 L/day after two years.
Special Populations and Conditions

11•

Pediatrics (< 18 years of age): The pharmacokinetics of Minjuvi has not been studied inpediatric patients.

•

Geriatrics (≥ 65 years of age): Age had no relevant effect on the pharmacokinetics of
Minjuvi.

•

Sex: Sex had no relevant effect on the pharmacokinetics of Minjuvi.

•

Pregnancy and Breast-feeding: The pharmacokinetics of Minjuvi in patients who are
pregnant or breast-feeding has not been studied.

•

Ethnic Origin: The pharmacokinetics of Minjuvi has not evaluated based on ethnic origin.

•

Hepatic Insufficiency: The effect of hepatic impairment was not formally tested in dedicatedclinical trials; however, no clinically meaningful differences in the pharmacokinetics oftafasitamab were observed for mild hepatic impairment (total bilirubin ≤ ULN and
AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST). The effect of moderate tosevere hepatic impairment (total bilirubin> 1.5 times ULN and any AST) on thepharmacokinetics of Minjuvi is unknown.

•

Renal Insufficiency: The effect of renal impairment was not formally tested in dedicatedclinical trials; however, no clinically meaningful differences in the pharmacokinetics oftafasitamab were observed for mild to moderate renal impairment (CrCL ≥ 30 and< 90 mL/min estimated by the Cockcroft-Gault equation). The effect of severe renal
impairment to end-stage renal disease (CrCL < 30 mL/min) on the pharmacokinetics of
Minjuvi is unknown.

•

Obesity: Weight had a statistically significant effect on the pharmacokinetics of Minjuvi in a
population pharmacokinetic model; however, the effect was not considered clinically
relevant in patients who weigh less than 163 kg. The clinical relevance in patients who weigh
163 kgs or greater is unknown.

STORAGE, STABILITY AND DISPOSALStore in a refrigerator (2°C – 8°C).
Keep the vial in the outer carton in order to protect from light.

MINJUVI™ (tafasitamab)

Page 19 of 30

Reconstituted solution (prior to dilution)
From a microbiological point of view, the reconstituted Minjuvi solution should be used as soon as
possible after reconstitution. If not used immediately, the reconstituted product may be stored prior todilution for up to 24 hours at 2°C - 25°C. Do not freeze or shake. Protect from light during storage.
Diluted solution (solution for infusion)
From a microbiological point of view, once diluted, the product should be used immediately. If not used
immediately, the infusion solution may be stored for a maximum of 36 hours at 2°C - 8°C followed by up
to 24 hours at up to 25°C. Do not freeze or shake. Protect from light during storage.

MINJUVI™ (tafasitamab)

Page 20 of 30

PART II: SCIENTIFIC INFORMATION
13

PHARMACEUTICAL INFORMATION

Drug Substance
Proper name: tafasitamab for injection
Molecular mass: Tafasitamab has a molecular weight of approximately 150 kDa.
Molecular formula: C6538H10068N1720O2046S52
Structure: Tafasitamab is a fragment crystallizable (Fc)-engineered humanized monoclonal antibody. It
is derived from the murine monoclonal antibody (mAb) 4G7 by humanization of the variable domain.
Drug Product Characteristics
Tafasitamab is expressed in Chinese hamster ovary (CHO) cells. Tafasitamab drug product (DP) is alyophilized powder for reconstitution and intravenous infusion. Tafasitamab DP is a white to slightly
yellowish lyophilizate for reconstitution. After reconstitution, tafasitamab is presented at aconcentration of 40 mg/mL in a 25 mM citrate buffered, isotonic solution at pH 6.0 supplied in singleuse 20 R glass vials.
14

CLINICAL TRIALS

14.1 Trial Design and Study Demographics
Tafasitamab plus lenalidomide followed by tafasitamab monotherapy was studied in the MOR208C203(L-MIND) study (NCT02399085), an open-label multicentre single-arm study. Adult patients were eligible
for the study if they had relapsed or refractory DLBCL, had received 1 to 3 prior systemic DLBCL
therapies, and, who at the time of the trial, were not candidates for high dose chemotherapy followed
by ASCT. At least one of the prior systemic therapies had to include a CD20 targeted therapy. Patientswere not eligible if they had other types of lymphoma including primary mediastinal B-cell lymphoma(PMBCL) or Burkitt lymphoma or if they had a history of double/triple hit genetics (i.e., detection of MYC
with BCL2 and/or BCL6 translocations). Patients with a history of CNS lymphoma involvement were also
excluded.
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 administered ondays 1 and 15 of each cycle until disease progression. Pre-medication, including antipyretics, histamine
H1 and H2 receptor blockers and glucocorticosteroids, was given 30 to 120 minutes prior to the first
three tafasitamab infusions.
Patients self-administered 25 mg lenalidomide daily on days 1 to 21 of each 28-day cycle, for up to
12 cycles.
A total of 81 patients were enrolled in the study. Seventy-one of the enrolled patients had DLBCL
confirmed by a central laboratory, and received combination treatment on study. The median age was
71 years (range 41 to 86 years), 87% were white and 55% were male. The median number of priorMINJUVI™ (tafasitamab)

Page 21 of 30

therapies was two and all patients had received a prior CD20-containing therapy. Fourteen patients(19.7%) had a primary refractory disease, 32 (45.1%) were refractory to their last prior therapy and 30(42.3%) were refractory to rituximab. Nine patients (12.7%) had received prior ASCT. The primaryreasons for patients (full analysis set) not being candidates for ASCT included age (46.5%), refractory tosalvage chemotherapy (26.8%), comorbidities (12.7%) and refusal of high dose chemotherapy/ASCT(12.7%).
The median duration of exposure to tafasitamab and lenalidomide was 6.7 months. Twenty-six (36.6%)
patients completed 12 cycles of tafasitamab. Twenty-three (32.4%) patients completed 12 cycles oflenalidomide.
14.2

Study Results

The primary efficacy outcome in the L-MIND study was the best Overall Response Rate (ORR), defined as
the sum of the proportions of patients who were complete or partial responders as assessed by anindependent review committee who applied the International Working Group Response Criteria (Cheson2007). Study Results are summarized in Table 6.
Table 6:

Efficacy Results in L-MIND(N = 71)

Best objective response rate
Overall response rate, n (%)
38 (53.5)(95% CI)(41.3,65.5)
Complete response rate, n (%)
25 (35.2)(95% CI)(24.2,47.5)
Partial response rate, n (%)
13 (18.3)(95% CI)(10.1,29.3)
Overall duration of response (complete + partial response)
Median, months2
34.6(95% CI)(21.7, not reached)(range, months)
0, 34.6
Duration of response in patients with complete response as
best response
Median, months2
NR(95% CI)(26.1, NR)(range, months)
0+, 34.1+
Duration of response in patients with partial response as
best response
Median, months2
5.7(95% CI)(1.8, NR)(range, months)
0+, 34.6
1 Confidence interval based on the Clopper-Pearson method.
2
Kaplan-Meier estimates. Confidence interval based on the Brookmeyer and Crowley method.
+ Denotes a censored observation.
1

MINJUVI™ (tafasitamab)

Page 22 of 30

14.4 Immunogenicity
As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody
formation is highly dependent on the sensitivity and specificity of the assay.
Seventeen of 245 evaluable subjects (6.9%) tested ADA-positive before start of tafasitamab treatment
suggesting the presence of pre-existing antibodies. Six subjects who had pre-existing ADAs were ADApositive on an intermittent basis also after start of tafasitamab treatment. The remaining 11 of baseline
ADA-positive subjects did not test positive for ADA during treatment. No baseline ADA-negative subjects
tested positive for ADA during treatment. Thus, no treatment-emergent or treatment-boosted ADAs
were detected. The ADA titers were low and there was no apparent clinical impact of ADAs on PK, safety
or efficacy.
15 MICROBIOLOGY
No microbiological information is required for this drug product.
16

NON-CLINICAL TOXICOLOGY

General Toxicology: Tafasitamab has shown to be highly specific to the CD19 antigen on B cells. Toxicity
studies following intravenous administration to cynomolgus monkeys have shown no other effect thanthe expected pharmacological depletion of B-cells in peripheral blood and in lymphoid tissues. Thesechanges reversed after cessation of treatment.
Carcinogenicity: Carcinogenicity studies have not been conducted with tafasitamab; consistent withhealth authority guidelines for therapeutics intended for the treatment of cancer, carcinogenicity
studies are generally not warranted.
Genotoxicity: Genotoxicity studies have not been conducted with tafasitamab; consistent with healthauthority guidelines for biotechnology products, genotoxicity studies are generally not needed.
Reproductive and Developmental Toxicology: No specific studies of fertility or reproductive anddevelopmental toxicity were conducted with tafasitamab. In the 13-week repeat-dose general toxicity
study in cynomolgus monkeys, no adverse effects on male and female reproductive organs wereobserved up to the highest dose tested, 100 mg/kg/week (approximately 9 times the human exposure
based on AUC at the clinical dose of 12 mg/kg/week).
Immunogenicity: In the 13-week repeat-dose general toxicity study in cynomolgus monkeys, there wasevidence for anti-drug antibody formation but no evidence for cytokine release. There was a reversible
reduction in a primary antibody response to antigens in a T-cell dependent antibody response
assessment.
17

SUPPORTING PRODUCT MONOGRAPHS

1. Product Monograph, REVLIMID (lenalidomide) Capsules, 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg,
Antineoplastic Agent, Immunomodulatory Agent, Celgene Inc. Control No. 229241, Revision Date: 20
August 2019

MINJUVI™ (tafasitamab)

Page 23 of 30

PATIENT MEDICATION INFORMATIONREAD THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINEPR

Minjuvi™

tafasitamab for injection
Read this carefully before you start taking Minjuvi and each time you get a refill. This leaflet is asummary and will not tell you everything about this drug. Talk to your healthcare professional about
your medical condition and treatment and ask if there is any new information about Minjuvi.
Serious Warnings and Precautions•

Infections: Fatal, life threatening, or serious infections have been reported in patients treated with
Minjuvi (see Section What are possible side effects from using Minjuvi?)•

Decreased production of blood cells: Serious and severe reduction in blood cells have beenreported in patients treated with Minjuvi (see Section What are possible side effects from using
Minjuvi?)•

A serious and life-threatening brain condition called progressive multifocal leukoencephalopathy(PML) has been observed after treatment with Minjuvi (see Section What are possible side effects
from using Minjuvi?)•

Recurrence of hepatitis B viral infection can occur with Minjuvi treatment (see Section What are
possible side effects from using Minjuvi?)

What is Minjuvi used for?
•Diffuse large B-cell lymphoma (DLBCL) – a type of cancer found mainly in the lymph nodes made up
of white blood cells that have become malignant. Minjuvi can be used to treat adult patients who
have had their cancer return after other treatments or when other treatments did not work.

“For the following indication, Minjuvi™ has been approved with conditions (NOC/c). This means it
has passed Health Canada’s review and can be bought and sold in Canada, but the manufacturer has
agreed to complete more studies to make sure the drug works the way it should. For more
information, talk to your healthcare professional.”•

Minjuvi (tafasitamab for injection) is indicated in combination with lenalidomide for thetreatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma(DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, who are
not eligible for autologous stem cell transplant (ASCT).

MINJUVI™ (tafasitamab)

Page 24 of 30

A Notice of Compliance with Conditions (NOC/c) is a type of approval to sell a drug in Canada.
Health Canada only gives an NOC/c to a drug that treats, prevents, or helps identify a serious or
life-threatening illness. The drug must show promising proof that it works well, is of high quality, and isreasonably safe. Also, the drug must either respond to a serious medical need in Canada, or be muchsafer than existing treatments.
Drug makers must agree in writing to clearly state on the label that the drug was given an NOC/c, tocomplete more testing to make sure the drug works the way it should, to actively monitor the drug’s
performance after it has been sold, and to report their findings to Health Canada.

MINJUVI™ (tafasitamab)

Page 25 of 30

How does Minjuvi work?
Minjuvi contains the active substance tafasitamab, an anti-cancer agent, which is a monoclonal antibody
that has been designed to kill cancer cells. The monoclonal antibody acts by binding to a protein on thesurface of cancerous B cells in order to kill the cells and to recruit normal immune cells, which also cantarget and kill the cancer cells. A monoclonal antibody is a protein that binds to a specific protein target.
Minjuvi is given with another drug called lenalidomide. Minjuvi in combination with lenalidomide
resulted in better cancer cell toxicity in laboratory studies than when either drug was used by itself.
What are the ingredients in Minjuvi?
Medicinal ingredients: tafasitamab
Non-medicinal ingredients: citric acid monohydrate, polysorbate 20, sodium citrate dihydrate, andtrehalose dihydrate.
Minjuvi comes in the following dosage forms:
For injection: 200 mg of tafasitamab as white to slightly yellowish lyophilized powder in single-dose vial
for reconstitution and further dilution
Do not use Minjuvi if:
You are allergic to tafasitamab or to any of the other ingredients in the medicine.
To help avoid side effects and ensure proper use, talk to your healthcare professional before you take
Minjuvi. Talk about any health conditions or problems you may have, including if you:•have an active infection or have had one recently.

•

have hepatitis B or have recovered from hepatitis B in the past.

•

are pregnant or plan to become pregnant. Minjuvi may harm your unborn baby. You should not
become pregnant during treatment with Minjuvi. Do not receive treatment with Minjuvi in
combination with lenalidomide if you are pregnant because lenalidomide can cause birthdefects and death of your unborn baby.

••

you should use an effective method of birth control (contraception) during treatment andfor at least 3 months after your last dose of Minjuvi.

•

tell your healthcare professional right away if you become pregnant or think you may be
pregnant during treatment with Minjuvi.

are breast-feeding or plan to breast-feed. It is not known if Minjuvi passes into your breast-milk.
Do not breast-feed during treatment and for at least 3 months after your last dose of Minjuvi.

Other warnings you should know about:•Infusion-related reactions
o Your healthcare provider will monitor you for infusion reactions during your infusion of
Minjuvi. Tell your health care provider right away if you get chills, flushing, headache, or
shortness of breath during an infusion with Minjuvi.

•

Low blood cell counts (platelets, red blood cells, and white blood cells)

MINJUVI™ (tafasitamab)

Page 26 of 30

•

Low blood cell counts are common with Minjuvi, but can also be serious or severe. Your
healthcare provider will monitor your blood counts during treatment with Minjuvi. Tell
your healthcare provider right away if you get a fever of 38°C or above, or any bruisingor bleeding.
Infectionso Serious infections, including infections that can cause death, have happened in people
during treatment with Minjuvi and after the last dose. Tell your healthcare provider
right away if you get a fever of 38°C or above, or develop any signs or symptoms ofinfection.

•

Hepatitis B reactivation

o

o

•

Progressive multifocal leukoencephalopathy
o

•

•

•

A serious and life-threatening brain condition called progressive multifocal
leukoencephalopathy (PML) has been observed after treatment with Minjuvi. Tell yourdoctor immediately if you have memory loss, trouble thinking, difficulty with walking,clumsiness, experience falls or weakness on one side of the body, changes in mood orloss of vision. Your doctor will check if you need to see a neurologist.

Tumor Lysis Syndrome (also called TLS) (the development of unusual levels of some chemicals
such as potassium and uric acid, in the blood caused by fast breakdown of cancer cells during
treatment)o Your healthcare provider will do blood tests to check for TLS.
o•Patients who have previously had hepatitis B may be at greater risk of hepatitis B
reactivation after receiving Minjuvi. Hepatitis B reactivation has been observed after
treatment with Minjuvi. Your doctor will monitor you for hepatitis B and may makechanges to your treatment if necessary.

Tell your doctor immediately if you have palpitations/irregular heartbeats; vomiting;fatigue/weakness; difficulty concentrating/trouble thinking; swelling, numbness ortingling in hands, face or feet; back pain; muscle cramps; fainting or trouble breathing.

Sexual Healtho Women should use an effective method of birth control during treatment and for3 months after your final dose of Minjuvi.
o No information is available to evaluate the potential effects of Minjuvi on fertility.
Pregnancyo Your healthcare professional should do a pregnancy test before you start treatment
with Minjuvi. Minjuvi can harm your unborn baby or cause loss of your pregnancy(miscarriage). You should not become pregnant during treatment with Minjuvi. Tell yourhealthcare professional right away if you become pregnant or think that you may be
pregnant.
Breast-feedingo It is unknown if Minjuvi can pass into breast-milk. Do not breastfeed for at least
3 months after your final dose of Minjuvi.

MINJUVI™ (tafasitamab)

Page 27 of 30

•Immunizationso The safety of immunization with live vaccines following tafasitamab therapy has notbeen investigated, and vaccination with live vaccines is not recommended concurrently
with tafasitamab therapy.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins,
minerals, natural supplements or alternative medicines.
The following may interact with Minjuvi:
No known interactions
How to take Minjuvi:•

Minjuvi will be given to you by your healthcare professional in a healthcare setting. Minjuvi isgiven as an intravenous infusion.

Usual dose:
•
•

•

•

Minjuvi 12 mg per kilogram (mg/kg) body weight is given as an intravenous infusion according to
the dosing schedule in Table 7.
You will receive other medications prior to each dose of Minjuvi to reduce the chances of an
infusion reaction. Your health care professional may decide you do not need these medicines after
several infusions if you do not have any reactions to the infusion.
Minjuvi is given while you are taking another drug called lenalidomide. The dose of lenalidomide is
25 mg and it is taken by mouth once a day for the first 21 days of each cycle for a maximum of 12
cycles. You should also read the PATIENT MEDICATION INFORMATION for lenalidomide before
starting treatment.
After a maximum of 12 cycles of Minjuvi and lenalidomide, Minjuvi is given alone. Treatment isusually continued until disease progression or unacceptable toxicity.

Table 7:

Minjuvi Dosing Schedule

Cycle
Cycle 1
Cycles 2 and 3
Cycle 4 and beyond

Dosing ScheduleDays 1, 4, 8, 15 and 22
Days 1, 8, 15 and 22
Days 1 and 15

Overdose:
Minjuvi is administered by your healthcare professional. There is no information on overdose with
Minjuvi. For management of a suspected drug overdose contact your healthcare professional,
hospital emergency department or regional poison control centre immediately, even if there are no
symptoms.
What are possible side effects from using Minjuvi?
These are not all the possible side affects you may feel when taking Minjuvi. If you experience any side
effects not listed here, contact your healthcare professional.
The most common side effects of Minjuvi include:

MINJUVI™ (tafasitamab)

Page 28 of 30

o
o
o
o
o
o
o
o
o
o
o

decreased blood count (certain white blood cells and red blood cells)
feeling tired or weakdecreased platelets
diarrhea, constipation, nausea, vomiting
coughtrouble breathingfever
swelling of lower legs or hands
respiratory tract infection
urinary tract infections
decreased appetite

Symptom / effectSerious side effects and what to do about them
Talk to your healthcare professional
Only if severe

In all cases

Stop taking drug and
get immediate
medical help

VERY COMMON
Infections- symptoms may include, fever,chills, sore throat, cough,shortness of breath, nausea,
vomiting, diarrhea
Low blood cell counts- symptoms may include feeling
tired or weak, fever, bleeding or
bruising√√

COMMON
Infusion reactions- symptoms include fever, chills,
rash, flushing, headache, or
shortness of breath within
24 hours of infusion
Hepatitis B reactivation- symptoms may include mild
fever, feeling of sickness, fatigue,
loss of appetite, joint and/or
abdominal pain and yellowing ofwhites of the eyes, skin andtongue.
Progressive multifocal
leukoencephalopathy (PML)MINJUVI™ (tafasitamab)

√

√

√

Page 29 of 30

- symptoms may include increasing
weakness or numbness of part or
all of one side of the body, loss ofvision or blurred vision,
unexplained dizziness and/orclumsiness or sudden falls, trouble
with thinking or memory, changes
in mood, change in vision, change
in mental status (for example,
confusion), seizures.
If you have a troublesome symptom or side effect that is not listed here or becomes bad enough tointerfere with your daily activities, talk to your healthcare professional.
Reporting Side Effects
You can report any suspected side effects associated with the use of health products to Health
Canada by:• Visiting the Web page on Adverse Reaction Reporting (https://www.canada.ca/en/healthcanada/services/drugs-health-products/medeffect-canada.html) for information on how toreport online, by mail or by fax; or• Calling toll-free at 1-866-234-2345.
NOTE: Contact your health professional if you need information about how to manage your side
effects. The Canada Vigilance Program does not provide medical advice.
Storage:
Minjuvi is stored refrigerated at 2°C to 8°C in the original carton to protect from light. Do not shake. Do
not freeze.
Keep out of reach and sight of children.
If you want more information about Minjuvi:••

Talk to your healthcare professional
Find the full product monograph that is prepared for healthcare professionals and includes thisPatient Medication Information by visiting the Health Canada website:(https://www.canada.ca/en/health-canada/services/drugs-health-products/drugproducts/drug-product-database.html), the manufacturer’s website(www.incytebiosciences.ca), or by calling 1-833-309-2759.

This leaflet was prepared by Incyte Corporation
Wilmington, Delaware 19803 USA
All trademarks used under license.
Last Revised: AUGUST 19, 2021
MINJUVI™ (tafasitamab)

Page 30 of 30