6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

•: Ocular toxicity [see Warnings and Precautions (5.1)].
•: Thrombocytopenia [see Warnings and Precautions (5.3)].
•: Infusion-related reactions [see Warnings and Precautions (5.4)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The pooled safety population described in Warnings and Precautions reflects exposure to BLENREP at a dosage of 2.5 mg/kg or 3.4 mg/kg (1.4 times the recommended dose) administered intravenously once every 3 weeks in 218 patients in DREAMM-2. Of these patients, 194 received a liquid formulation (not the approved dosage form) rather than the lyophilized powder. Among the 218 patients, 24% were exposed for 6 months or longer.

Relapsed or Refractory Multiple Myeloma

The safety of BLENREP as a single agent was evaluated in DREAMM-2 [see Clinical Studies (14.1)]. Patients received BLENREP at the recommended dosage of 2.5 mg/kg administered intravenously once every 3 weeks (n = 95). Among these patients, 22% were exposed for 6 months or longer.

Serious adverse reactions occurred in 40% of patients who received BLENREP. Serious adverse reactions in >3% of patients included pneumonia (7%), pyrexia (6%), renal impairment (4.2%), sepsis (4.2%), hypercalcemia (4.2%), and infusion-related reactions (3.2%). Fatal adverse reactions occurred in 3.2% of patients, including sepsis (1%), cardiac arrest (1%), and lung infection (1%).

Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received BLENREP; keratopathy (2.1%) was the most frequent adverse reaction resulting in permanent discontinuation.

Dosage interruptions due to an adverse reaction occurred in 54% of patients who received BLENREP. Adverse reactions which required a dosage interruption in >3% of patients included keratopathy (47%), blurred vision (5%), dry eye (3.2%), and pneumonia (3.2%).

Dose reductions due to an adverse reaction occurred in 29% of patients. Adverse reactions which required a dose reduction in >3% of patients included keratopathy (23%) and thrombocytopenia (5%).

The most common adverse reactions (≥20%) were keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue. The most common Grade 3 or 4 (≥5%) laboratory abnormalities were lymphocytes decreased, platelets decreased, hemoglobin decreased, neutrophils decreased, creatinine increased, and gamma-glutamyl transferase increased.

Table 3 summarizes the adverse reactions in DREAMM-2 for patients who received the recommended dosage of 2.5 mg/kg once every 3 weeks.

Table 3. Adverse Reactions (≥10%) in Patients Who Received BLENREP in DREAMM-2
a Keratopathy was based on slit lamp eye examination, characterized as corneal epithelium changes with or without symptoms. b Visual acuity changes were determined upon eye examination. c Blurred vision included diplopia, vision blurred, visual acuity reduced, and visual impairment. d Dry eyes included dry eye, ocular discomfort, and eye pruritus. e Fatigue included fatigue and asthenia. f Infusion-related reactions included infusion-related reaction, pyrexia, chills, diarrhea, nausea, asthenia, hypertension, lethargy, tachycardia. g Upper respiratory tract infection included upper respiratory tract infection, nasopharyngitis, rhinovirus infections, and sinusitis.
Adverse Reactions	BLENREP N = 95
Adverse Reactions	All Grades (%)	Grade 3-4 (%)
Eye disorders
Keratopathya	71	44
Decreased visual acuityb	53	28
Blurred visionc	22	4
Dry eyesd	14	1
Gastrointestinal disorders
Nausea	24	0
Constipation	13	0
Diarrhea	13	1
General disorders and administration site conditions
Pyrexia	22	3
Fatiguee	20	2
Procedural complications
Infusion-related reactionsf	21	3
Musculoskeletal and connective tissue disorders
Arthralgia	12	0
Back pain	11	2
Metabolic and nutritional disorders
Decreased appetite	12	0
Infections
Upper respiratory tract infectiong	11	0

Clinically relevant adverse reactions in <10% of patients included:

Eye Disorders: Photophobia, eye irritation, infective keratitis, ulcerative keratitis.

Gastrointestinal Disorders: Vomiting.

Infections: Pneumonia.

Renal and Urinary Disorders: Albuminuria.

Table 4 summarizes the laboratory abnormalities in DREAMM-2.

Table 4. Laboratory Abnormalities (≥20%) Worsening from Baseline in Patients Who Received BLENREP in DREAMM-2
Laboratory Abnormality	BLENREP N = 95
Laboratory Abnormality	All Grades (%)	Grades 3-4 (%)
Hematology
Platelets decreased	62	21
Lymphocytes decreased	49	22
Hemoglobin decreased	32	18
Neutrophils decreased	28	9
Chemistry
Aspartate aminotransferase increased	57	2
Albumin decreased	43	4
Glucose increased	38	3
Creatinine increased	28	5
Alkaline phosphatase increased	26	1
Gamma-glutamyl transferase increased	25	5
Creatinine phosphokinase increased	22	1
Sodium decreased	21	2
Potassium decreased	20	2

Clinically relevant adverse reactions from expanded access programs include: pneumonitis including fatal cases.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. 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 products may be misleading.

The immunogenicity of BLENREP was evaluated using an electrochemiluminescence (ECL)-based immunoassay to test for anti-belantamab mafodotin antibodies. In clinical studies of BLENREP, 2/274 patients (<1%) tested positive for anti-belantamab mafodotin antibodies after treatment. One of the 2 patients tested positive for neutralizing anti-belantamab mafodotin antibodies following 4 weeks on therapy. Due to the limited number of patients with antibodies against belantamab mafodotin-blmf, no conclusions can be drawn concerning a potential effect of immunogenicity on pharmacokinetics, efficacy, or safety.