6 ADVERSE 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)]

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 was evaluated in L-MIND [see Clinical Studies (14)]. 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%), 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 interruption 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, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.

Table 3 summarizes the adverse reactions in L-MIND.

Table 3: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Who Received MONJUVI in L-MIND
Adverse Reaction	MONJUVI (N=81)
Adverse Reaction	All Grades (%)	Grade 3 or 4 (%)
* Fatigue includes asthenia and fatigue † Abdominal pain includes abdominal pain, abdominal pain lower, and abdominal pain upper ‡ Respiratory tract infection includes: lower respiratory tract infection, upper respiratory tract infection, respiratory tract infection § Urinary tract infection includes: urinary tract infection, Escherichia urinary tract infection, urinary tract infection bacterial, urinary tract infection enterococcal ¶ Rash includes rash, rash maculo-papular, rash pruritic, rash erythematous, rash pustular
Blood and lymphatic system disorders
Neutropenia	51	49
Anemia	36	7
Thrombocytopenia	31	17
Febrile neutropenia	12	12
General disorders and administration site conditions
Fatigue*	38	3.7
Pyrexia	24	1.2
Peripheral edema	24	0
Gastrointestinal disorders
Diarrhea	36	1.2
Constipation	17	0
Abdominal pain†	15	1.2
Nausea	15	0
Vomiting	15	0
Respiratory, thoracic and mediastinal disorders
Cough	26	1.2
Dyspnea	12	1.2
Infections
Respiratory tract infection‡	24	4.9
Urinary tract infection§	17	4.9
Bronchitis	16	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¶	15	2.5
Pruritus	10	1.2

Clinically relevant adverse reactions in <10% of patients who received MONJUVI 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 benign, malignant and unspecified: 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 4 summarizes the laboratory abnormalities in L-MIND.

Table 4: 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*
Laboratory Abnormality	All Grades (%)	Grade 3 or 4 (%)
* 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.
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

6.2 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 assays. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other tafasitamab products may be misleading.

Overall, no treatment-emergent or treatment-boosted anti-tafasitamab antibodies were observed. No clinically meaningful differences in the pharmacokinetics, efficacy, or safety profile of tafasitamab-cxix were observed in 2.5% of 81 patients with relapsed or refractory DLBCL with pre-existing anti-tafasitamab antibodies in L-MIND.