TAFASITAMAB: 1,392 Adverse Event Reports & Safety Profile

Tafasitamab-cxix is a humanized CD19-directed cytolytic monoclonal antibody that contains an IgG1/2 hybrid Fc-domain with 2 amino acid substitutions to modify the Fc-mediated functions of the antibody. It is produced by recombinant DNA technology in mammalian cells (Chinese hamster ovary). Tafasitamab-cxix has a molecular weight of approximately 150 kDa. MONJUVI (tafasitamab-cxix) for injection is supplied as a sterile, preservative-free, white to slightly yellowish lyophilized powder in a single-dose vial for intravenous use after reconstitution and further dilution. After reconstitution with 5 mL of Sterile Water for Injection, USP, the resulting concentration is 40 mg/mL with a pH of 6.0. Each single-dose vial contains 200 mg tafasitamab-cxix, citric acid monohydrate (3.7 mg), polysorbate 20 (1 mg), sodium citrate dihydrate (31.6 mg) and trehalose dihydrate (378.3 mg).

AND USAGE MONJUVI is a CD19-directed cytolytic antibody 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, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1.1 ) in combination with lenalidomide and rituximab for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). ( 1.2 ) Limitations of Use : MONJUVI is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials. ( 1.2 , 14.3 )

1.1 Relapsed or Refractory Diffuse Large B-cell Lymphoma MONJUVI, in combination with lenalidomide, is indicated 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, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate [ see Clinical Studies ( 14.1 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

1.2 Relapsed or Refractory Follicular Lymphoma MONJUVI, in combination with lenalidomide and rituximab, is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL). Limitations of Use : MONJUVI is not indicated and is not recommended for the treatment of patients with relapsed or refractory marginal zone lymphoma outside of controlled clinical trials <span class="opacity-50 text-xs">[see Clinical Studies ( 14.3 )]</span>.

AND ADMINISTRATION Administer premedications prior to starting MONJUVI. ( 2.4 )

See Full Prescribing

Information for instructions on preparation and administration. ( 2.6 )

Diffuse

Large B-cell Lymphoma The recommended dosage of MONJUVI is 12 mg/kg as an intravenous infusion according to the following dosing schedule: ( 2.2 )

Cycle

1: Days 1, 4, 8, 15, and 22 of the 28-day cycle.

Cycles

2 and 3: Days 1, 8, 15, and 22 of each 28-day cycle.

Cycle

4 and beyond: Days 1 and 15 of each 28-day cycle. Administer MONJUVI in combination with lenalidomide for a maximum of 12 cycles and then continue MONJUVI as monotherapy until disease progression or unacceptable toxicity. ( 2.2 )

Follicular Lymphoma

The recommended dosage of MONJUVI is 12 mg/kg as an intravenous infusion according to the following dosing schedule: ( 2.3 )

Cycles

1 to 3: Days 1, 8, 15, and 22 of each 28-day cycle.

Cycles

4 to 12: Days 1 and 15 of each 28-day cycle. Administer MONJUVI in combination with lenalidomide (Cycles 1 to 12) and rituximab (Cycles 1 to 5). ( 2.3 )

2.1 Important Dosing Information MONJUVI should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>.

2.2 Recommended Dosage for Relapsed or Refractory Diffuse Large B‑cell Lymphoma The recommended dose of MONJUVI is 12 mg/kg based on actual body weight administered as an intravenous infusion in combination with lenalidomide, according to the dosing schedule in Table 1.

Table

1: MONJUVI Dosing Schedule for Patients with Relapsed or Refractory DLBCL Cycle Each treatment cycle is 28 days.

Dosing Schedule Cycle

1 Days 1, 4, 8, 15, and 22 Cycles 2 and 3 Days 1, 8, 15, and 22 Cycle 4 and beyond Days 1 and 15 Administer MONJUVI in combination with lenalidomide 25 mg for a maximum of 12 cycles, then continue MONJUVI as monotherapy until disease progression or unacceptable toxicity [see Clinical Studies ( 14 .1 )] . Refer to the lenalidomide prescribing information for lenalidomide dosage recommendations, including for patients with renal insufficiency.

2.3 Recommended Dosage for Relapsed or Refractory Follicular Lymphoma The recommended dose of MONJUVI is 12 mg/kg based on actual body weight administered as an intravenous infusion in combination with lenalidomide and rituximab, according to the dosing schedule in Table 2.

Table

2: MONJUVI Dosing Schedule for Patients with Relapsed or Refractory FL Cycle Each treatment cycle is 28 days.

Dosing Schedule Cycles

1 to 3 Days 1, 8, 15, and 22 Cycles 4 to 12 Days 1 and 15 Administer MONJUVI in combination with lenalidomide 20 mg (Days 1-21 in Cycles 1 to 12) and rituximab 375 mg/m 2 (Cycles 1 to 5) [see Clinical Studies ( 14.2 )] . Refer to the rituximab prescribing information and the lenalidomide prescribing information for the respective dosage recommendations, including lenalidomide dosage recommendations for patients with renal insufficiency.

2.4 Recommended Premedications and Prophylactic Medication Premedication Administer premedications 30 minutes to 2 hours prior to starting MONJUVI infusion to minimize infusion-related reactions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>. Premedications may include acetaminophen, histamine H 1 receptor antagonists, histamine H 2 receptor antagonists, and/or glucocorticosteroids. For patients not experiencing infusion-related reactions during the first 3 infusions, premedication is optional for subsequent infusions. If a patient experiences an infusion-related reaction, administer premedications before each subsequent infusion.

Thromboprophylaxis

Refer to the lenalidomide prescribing information for recommendations on prophylaxis for venous and arterial thrombotic events.

2.5 Dosage Modifications for Adverse Reactions The recommended dosage modifications for adverse reactions are summarized in Table 3.

Table

3: Dosage Modifications for Adverse Reactions Adverse Reaction Severity MONJUVI Dosage Modification Infusion-related reactions [see Warnings and Precautions ( 5.1 )] Ensure premedications administered before subsequent infusions [see Dosage and Administration (2.4)].

Grade

2 (moderate) 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 the reaction occurred. If the patient does not experience further reaction within 1 hour and vital signs are stable, the infusion rate may be increased every 30 minutes as tolerated to the rate at which the reaction occurred.

Grade

3 (severe) 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 the reaction occurred. If the patient does not experience further reaction within 1 hour and 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 Grade

3 reaction returns, stop the infusion immediately and permanently discontinue MONJUVI.

Grade

4 (life-threatening) Stop the infusion immediately and permanently discontinue MONJUVI. Myelosuppression [see Warnings and Precautions ( 5.2 )] Platelet count of 50,000/mcL or less Withhold MONJUVI and lenalidomide and monitor complete blood count (CBC) weekly until platelet count is 50,000/mcL or higher. Resume MONJUVI at the same dose and lenalidomide at a reduced dose. Refer to lenalidomide prescribing information for dosage modifications. Neutrophil count of 1,000/ mcL or less for at least 7 days OR Neutrophil count of 1,000/ mcL or less with an increase of body temperature to 100.4°F (38°C) or higher OR Neutrophil count less than 500/mcL Withhold MONJUVI and lenalidomide and monitor CBC weekly until neutrophil count is 1,000/ mcL or higher. Resume MONJUVI at the same dose and lenalidomide at a reduced dose. Refer to lenalidomide prescribing information for dosage modifications.

2.6 Preparation and Administration Reconstitute and dilute MONJUVI prior to infusion.

Reconstitution

Calculate the dose (mg) and determine the number of vials needed. Reconstitute each 200 mg MONJUVI vial with 5 mL Sterile Water for Injection, USP with the stream directed toward the wall of each vial to obtain a final concentration of 40 mg/mL tafasitamab-cxix. Gently swirl the vial(s) until completely dissolved. Do not shake or swirl vigorously. Complete dissolution may take up to 5 minutes. Visually inspect the reconstituted solution for particulate matter or discoloration. The reconstituted solution should appear as a colorless to slightly yellow solution. Discard the vial(s) if the solution is cloudy, discolored, or contains visible particles. Use the reconstituted MONJUVI solution immediately. If needed, store the reconstituted solution in the vial for a maximum of 12 hours either refrigerated at 36°F to 46°F (2°C to 8°C) or room temperature at 68°F to 77°F (20°C to 25°C) before dilution. Protect from light during storage.

Dilution

Determine the volume (mL) of the 40 mg/mL reconstituted MONJUVI solution needed based on the required dose. Remove a volume equal to the required MONJUVI solution from a 250 mL 0.9% Sodium Chloride Injection, USP infusion bag and discard it. Withdraw the necessary amount of MONJUVI and slowly dilute in the infusion bag that contains the 0.9% Sodium Chloride Injection, USP to a final concentration of 2 mg/mL to 8 mg/mL. Discard any unused portion of MONJUVI remaining in the vial. Gently mix the intravenous bag by slowly inverting the bag. Do not shake . Visually inspect the infusion bag with the diluted MONJUVI infusion solution for particulate matter and discoloration prior to administration. If not used immediately, store the diluted MONJUVI infusion solution refrigerated for up to 18 hours at 36°F to 46°F (2°C to 8°C) and/or at room temperature for up to 12 hours at 68°F to 77°F (20°C to 25°C). The room temperature storage includes time for infusion. Protect from light during storage. Do not shake or freeze the reconstituted or diluted infusion solutions.

Administration

Administer MONJUVI as an intravenous infusion. For the first infusion, use an infusion rate of 70 mL/h for the first 30 minutes, then, increase the rate so that the infusion is administered within 1.5 to 2.5 hours. Administer all subsequent infusions within 1.5 to 2 hours. Infuse the entire contents of the bag containing MONJUVI. Do not co-administer other drugs through the same infusion line. No incompatibilities have been observed between MONJUVI with infusion containers made of polypropylene (PP), polyvinylchloride (PVC), polyethylene (PE), polyethylene terephthalate (PET), or glass and infusion sets made of polyurethane (PUR) or PVC.

None. None.

REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-related reactions [see Warnings and Precautions ( 5.1 )] Myelosuppression [see Warnings and Precautions ( 5.2 )] Infections [see Warnings and Precautions ( 5.3 )] The most common adverse reactions (≥ 20%) in patients with relapsed or refractory DLBCL are neutropenia, respiratory tract infection, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, and decreased appetite. ( 6.1 ) The most common adverse reactions (≥ 20%), excluding laboratory abnormalities, in patients with relapsed or refractory FL are respiratory tract infections, diarrhea, rash, fatigue, constipation, musculoskeletal pain, and cough. The most common Grade 3 or 4 laboratory abnormalities (≥ 20%) are decreased neutrophils and decreased lymphocytes. To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in other clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory Diffuse Large B-cell Lymphoma The safety of MONJUVI in patients with relapsed or refractory DLBCL was evaluated in L-MIND <span class="opacity-50 text-xs">[see Clinical Studies ( 14 .1 )]</span>. Patients (N = 81) received MONJUVI 12 mg/kg intravenously in combination with lenalidomide for a maximum of 12 cycles, followed by MONJUVI as monotherapy until disease progression or unacceptable toxicity as follows: Cycle 1: Days 1, 4, 8, 15, and 22 of the 28-day cycle; Cycles 2 and 3: Days 1, 8, 15, and 22 of each 28-day cycle; Cycles 4 and beyond: Days 1 and 15 of each 28-day cycle. Among patients who received MONJUVI, 57% were exposed for 6 months or longer, 42% were exposed for greater than one year, and 24% were exposed for greater than two years. Serious adverse reactions occurred in 52% of patients who received MONJUVI. Serious adverse reactions in ≥ 6% of patients included infections (26%), including pneumonia (7%) and febrile neutropenia (6%). Fatal adverse reactions occurred in 5% of patients who received MONJUVI, including cerebrovascular accident (1.2%), respiratory failure (1.2%), progressive multifocal leukoencephalopathy (1.2%), and sudden death (1.2%). Permanent discontinuation of MONJUVI or lenalidomide due to an adverse reaction occurred in 25% of patients and permanent discontinuation of MONJUVI due to an adverse reaction occurred in 15%. The most frequent adverse reactions which resulted in permanent discontinuation of MONJUVI were infections (5%), nervous system disorders (2.5%), and respiratory, thoracic and mediastinal disorders (2.5%). Dosage interruptions of MONJUVI or lenalidomide due to an adverse reaction occurred in 69% of patients and dosage interruptions of MONJUVI due to an adverse reaction occurred in 65%. The most frequent adverse reactions which required a dosage interruption of MONJUVI were blood and lymphatic system disorders (41%) and infections (27%). The most common adverse reactions (≥ 20%) were neutropenia, respiratory tract infection, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, and decreased appetite.

Table

4 summarizes the adverse reactions in L-MIND.

Table

4: Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Who Received MONJUVI in L-MIND Adverse Reaction MONJUVI in Combination with Lenalidomide (N = 81)

All

Grades (%)

Grade

3 or 4 (%) Blood and lymphatic system disorders Neutropenia 51 49 Anemia 36 7 Thrombocytopenia 31 17 Febrile neutropenia 12 12 Infections Respiratory tract infection Respiratory tract infection includes lower respiratory tract infection, upper respiratory tract infection, respiratory tract infection, bronchitis, pneumonia, nasopharyngitis, and related terms. 51 12 Urinary tract infection Urinary tract infection includes urinary tract infection, urinary tract infection bacterial, and related terms. 17

4.9 General disorders and administration site conditions Fatigue Fatigue includes asthenia and fatigue. 38

3.7 Pyrexia 24

1.2 Peripheral edema 24 0 Gastrointestinal disorders Diarrhea 36

1.2 Constipation 17 0 Abdominal pain Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper. 15

1.2 Nausea 15 0 Vomiting 15 0 Respiratory, thoracic and mediastinal disorders Cough 26

1.2 Dyspnea 12

1.2 Metabolism and nutrition disorders Decreased appetite 22 0 Hypokalemia 19 6 Musculoskeletal and connective tissue disorders Back pain 19

2.5 Muscle spasms 15 0 Skin and subcutaneous tissue disorders Rash Rash includes rash, rash maculopapular, rash pruritic, rash erythematous, and rash pustular. 15

2.5 Pruritus 10

1.2 Clinically relevant adverse reactions in &lt; 10% of patients with relapsed or refractory DLBCL who received MONJUVI in L-MIND were: Blood and lymphatic system disorders: lymphopenia (6%) General disorders and administration site conditions: infusion-related reaction (6%) Infections: sepsis (4.9%) Investigations: weight decreased (4.9%) Musculoskeletal and connective tissue disorders: arthralgia (9%), pain in extremity (9%), musculoskeletal pain (2.5%) Neoplasms: basal cell carcinoma (1.2%) Nervous system disorders: headache (9%), paresthesia (7%), dysgeusia (6%) Respiratory, thoracic and mediastinal disorders: nasal congestion (4.9%), exacerbation of chronic obstructive pulmonary disease (1.2%) Skin and subcutaneous tissue disorders: erythema (4.9%), alopecia (2.5%), hyperhidrosis (2.5%)

Table

5 summarizes the laboratory abnormalities in L-MIND.

Table

5: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma Who Received MONJUVI in L-MIND Laboratory Abnormality MONJUVI in Combination with Lenalidomide 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.

All

Grades (%)

Grade

3 or 4 (%)

Chemistry

Glucose increased 49 5 Calcium decreased 47

1.4 Gamma glutamyl transferase increased 34 5 Albumin decreased 26 0 Magnesium decreased 22 0 Urate increased 20 7 Phosphate decreased 20 5 Creatinine increased 20

1.4 Aspartate aminotransferase increased 20 0 Coagulation Activated partial thromboplastin time increased 46

4.1 Relapsed or Refractory Follicular Lymphoma The safety of MONJUVI in patients with relapsed or refractory FL was evaluated in the inMIND trial <span class="opacity-50 text-xs">[see Clinical Studies (14.2)]</span>. Patients received MONJUVI 12 mg/kg (N = 274) or placebo (N = 272) intravenously for a maximum of 12 cycles in combination with lenalidomide 20 mg (Days 1-21 of Cycles 1 to 12) and rituximab 375 mg/m 2 (Cycles 1 to 5). MONJUVI was administered as follows: Cycle 1 to 3: Days 1, 8, 15, and 22 of each 28-day cycle; Cycles 4 to 12: Days 1 and 15 of each 28-day cycle. In the MONJUVI arm, 54% of patients completed all 12 cycles. The median age in that arm was 64 years (range: 36-88 years); 20% were age 75 years or older; 55% were male; 80% were White, 15% Asian, and 0.4% Black. In the MONJUVI arm, serious adverse reactions occurred in 33% of patients, including serious infections in 24% of patients (including pneumonia and COVID-19 infection). Other serious adverse reactions in ≥ 2% of patients included renal insufficiency (3.3%), second primary malignancies (2.9%), and febrile neutropenia (2.6%). Fatal adverse reactions occurred in 1.5% of patients, including from COVID‑19, sepsis, and adenocarcinoma. Adverse reactions led to permanent discontinuation of MONJUVI in 11% of patients and dosage interruptions in 74%. The most frequent adverse reactions leading to dosage interruptions of MONJUVI were neutropenia (37% of all patients), COVID-19 (22%), pneumonia (11%), and infusion-related reaction (8%). The most common adverse reactions (≥ 20%) in recipients of MONJUVI, excluding laboratory abnormalities, were respiratory tract infections (including COVID-19 infection and pneumonia), diarrhea, rash, fatigue, constipation, musculoskeletal pain, and cough. The most common Grade 3 or 4 laboratory abnormalities (≥ 20%) were decreased neutrophils and decreased lymphocytes.

Table

6 summarizes the adverse reactions in inMIND. Adverse reactions occurring at least 5% more frequently in the MONJUVI arm included COVID-19 infection, pneumonia, diarrhea, pruritus, fatigue, musculoskeletal pain, and mucositis.

Table

6: Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory Follicular Lymphoma Who Received MONJUVI in inMIND Adverse Reaction MONJUVI in Combination with Lenalidomide and Rituximab (N = 274) Placebo in Combination with Lenalidomide and Rituximab (N = 272)

All

Grades (%)

Grade

3 or 4 (%)

All

Grades (%)

Grade

3 or 4 (%)

Infections

Respiratory tract infection 56 18 56 9 COVID-19 infection Includes COVID-19, COVID-19 pneumonia, and coronavirus test positive. 34 Includes 2 cases in each arm with fatal outcome. 10 24

2.9 Pneumonia Includes pneumonia, COVID-19 pneumonia, pneumonia fungal, Pneumocystis jirovecii pneumonia, and other types of pneumonia. 18 14 11 Includes 3 cases with fatal outcome, including 2 reported under COVID-19 infection. 7 Upper respiratory tract infection Includes upper respiratory tract infection, nasopharyngitis, sinusitis, laryngitis, and related terms. 17 1.1 22

0.4 Gastrointestinal disorders Diarrhea 38 0.7 28

1.8 Constipation 29 0.7 25 0 Nausea 18 0.4 14

0.4 Abdominal pain 13 0 18

2.2 Skin and subcutaneous tissue disorders Rash Includes rash, urticaria, dermatitis, drug eruption, and related terms. 37 3.6 33

1.5 Pruritus 16 0.4 10 0 General disorders Fatigue Includes fatigue and asthenia. 34 2.9 25

0.7 Pyrexia 19 1.8 16

2.2 Mucositis Includes oropharyngeal pain, stomatitis, mucosal inflammation, mouth ulceration, odynophagia, aphthous ulcer, esophageal pain, and related terms. 17 0.4 11 0 Edema Includes edema, peripheral edema, pulmonary edema, generalized edema, and related terms. 11 0.7 17

1.1 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes back pain, pain in extremity, myalgia, bone pain, neck pain, spinal pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, and sacral pain. 24 0.4 16

0.4 Muscle contracture Includes muscle spasms and muscle contractions involuntary. 18 0 19 0 Respiratory, thoracic and mediastinal disorders Cough 21 0 19 0 Procedural complications Infusion-related reaction Includes infusion-related reaction and cytokine release syndrome. 16 0.7 16

0.4 Nervous system disorders Peripheral neuropathy Includes peripheral neuropathy, paresthesia, peripheral sensory neuropathy, neuralgia, dysesthesia, hyperesthesia, and peripheral motor neuropathy. 12 0 11

0.4 Headache 10 0.4 7 0 Metabolism and nutrition disorders Decreased appetite 10 0 9

0.7 The table includes a combination of grouped and ungrouped terms. Adverse reactions were graded using NCI CTCAE version

5.0 In the MONJUVI arm, clinically relevant adverse reactions in &lt; 10% of patients with relapsed or refractory FL included thrombosis, febrile neutropenia, second primary malignancy, sepsis, interstitial lung disease, and tumor lysis syndrome.

Table

7 summarizes the laboratory abnormalities in inMIND.

Grade

4 laboratory abnormalities in > 1% of patients included neutrophils decreased (19%), platelets decreased (4%) and lymphocytes decreased (1.8%).

Table

7: Select Laboratory Abnormalities (> 20%) Worsening from Baseline in Patients with Relapsed or Refractory Follicular Lymphoma Who Received MONJUVI in inMIND Laboratory Abnormality MONJUVI in Combination with Lenalidomide and Rituximab The denominator used to calculate the rate varied from 268 - 274 based on the number of patients with a baseline value and at least 1 post-treatment value. Placebo in Combination with Lenalidomide and Rituximab All Grades (%)

Grade

3 or 4 (%)

All

Grades (%)

Grade

3 or 4 (%)

Hematology

Neutrophils decreased 75 48 71 44 Hemoglobin decreased 60 9 54 7 Lymphocytes decreased 57 22 51 19 Platelets decreased 40 8 43 9 Chemistry Alanine aminotransferase increased 47 1.5 42

1.5 Alkaline phosphatase increased 33 0 27 0 Creatinine increased 29 1.5 30

0.7 Aspartate aminotransferase increased 29 0 31

0.4 Glucose increased 28 0.4 28

1.1 Potassium decreased 24 3.3 24 3 Sodium decreased 24 1.5 22 0.4

AND PRECAUTIONS Infusion-Related Reactions : Monitor patients frequently during infusion. Interrupt or discontinue infusion based on severity. ( 2.5 , 5.1 ) Myelosuppression : Monitor complete blood counts. Manage using dose modifications and growth factor support. Interrupt or discontinue MONJUVI based on severity. ( 2.5 , 5.2 ) Infections : Bacterial, fungal and viral infections can occur during and following MONJUVI. Monitor patients for infections. ( 2.5 , 5.3 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.4 )

5.1 Infusion-Related Reactions MONJUVI can cause infusion-related reactions <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . In L-MIND, infusion-related reactions occurred in 6% of the 81 patients with DLBCL who received MONJUVI. Eighty percent of infusion-related reactions occurred during cycle 1 or 2. In inMIND, infusion-related reactions occurred in 16% of the 274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab. Signs and symptoms included fever, chills, rash, flushing, dyspnea, and hypertension. These reactions were generally managed with temporary interruption of the infusion and/or with supportive medication. Premedicate patients prior to starting MONJUVI infusion <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.4 )]</span> . Monitor patients frequently during infusion. Based on the severity of the infusion-related reaction, interrupt or discontinue MONJUVI [ see Dosage and Administration ( 2.5 )] . Institute appropriate medical management.

5.2 Myelosuppression MONJUVI can cause serious or severe myelosuppression, including neutropenia, lymphopenia, thrombocytopenia, and anemia [ see Adverse Reactions ( 6.1 ) ] . In L-MIND, among 81 patients with DLBCL who received MONJUVI, Grade 3 neutropenia was reported in 25%, Grade 3 thrombocytopenia in 12%, and Grade 3 anemia in 7%.

Grade

4 neutropenia was reported in 25% and Grade 4 thrombocytopenia in 6%. Neutropenia led to treatment discontinuation in 3.7% of the patients with DLBCL. Febrile neutropenia occurred in 12%. In inMIND, among 274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab, new or worsening Grade 3 or 4 cytopenias included decreased neutrophils in 48% (Grade 4, 19%), decreased lymphocytes in 22% (Grade 4, 1.8%), decreased hemoglobin in 9%, and decreased platelets in 8% (Grade 4, 4%). Febrile neutropenia occurred in 4.4%. Monitor CBCs before each treatment cycle and throughout treatment. Monitor patients with neutropenia for signs of infection. Consider granulocyte colony-stimulating factor administration. Withhold MONJUVI based on the severity of the adverse reaction [see Dosage and Administration ( 2.5 )]. Refer to the lenalidomide prescribing information for dosage modifications.

5.3 Infections Fatal and serious infections, including opportunistic infections, occurred in patients during treatment with MONJUVI and following the last dose [ see Adverse Reactions ( 6.1 )]. In L-MIND, 73% of the 81 patients with DLBCL who received MONJUVI developed an infection.

Grade

3 or higher infection occurred in 30%. Infection-related deaths occurred in 2.5% of patients, including a case of progressive multifocal leukoencephalophathy (PML). The most frequent Grade 3 or higher infection was pneumonia (7%). The most frequent infections of any grade were respiratory tract infections (51%, including pneumonias) and urinary tract infection (17%).

Among

274 patients with FL who received MONJUVI in combination with lenalidomide and rituximab in inMIND, Grade 3 or higher infections occurred in 24%, including fatal infections in 1.1% of patients. The most frequent Grade ≥ 3 infections were respiratory tract infections (19%), including Grade 3 or higher pneumonia (14%) and COVID-19 infection (11%). Opportunistic infections of any grade occurred in 6% of patients, including herpes simplex or zoster infection (5%), fungal pneumonia (1.1%, including Pneumocytis jirovecii pneumonia in 0.4%), and cytomegalovirus (CMV) reactivation (0.4%). Monitor patients for signs and symptoms of infection and manage infections as appropriate. Consider infection prophylaxis per institutional guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate.

5.4 Embryo-Fetal Toxicity Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MONJUVI and for 3 months after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 , 8.3 )]</span> . The combination of MONJUVI with lenalidomide and of MONJUVI with lenalidomide and rituximab is contraindicated in pregnant women because lenalidomide can cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.