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Relapsed or Refractory Multiple Myeloma
The safety of BLENREP as a single agent was evaluated in DREAMM-2 [ see Clinical Studies ( 14.1 ) of full Prescribing Information ]. 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 infusionrelated 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
BLENREP N = 95
Adverse Reactions
All Grades (%)
Grade 3-4 (%)
|
Eye disorders
Keratopathy a
|
71 |
44 |
Decreased visual acuity b
|
53 |
28 |
Blurred vision c
|
22 |
4 |
Dry eyes d
|
14 |
1 |
Gastrointestinal disorders Nausea |
24 |
0 |
Constipation |
13 |
0 |
Diarrhea |
13 |
1 |
General disorders and administration site conditions |
Pyrexia |
22 |
3 |
Fatigue e
|
20 |
2 |
Procedural complications Infusion-related reactions f
|
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 infection g
|
11 |
0 |
|
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 . |
Clinically relevant adverse reactions in < 10 % of patients included : |
Eye Disorders : Photophobia , eye irritation , infective keratitis , ulcerative keratitis . |
Gastrointestinal Disorders : Vomiting . |
Infections : Pneumonia . |
Investigations : 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 |
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 |
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 antibelantamab 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 .
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary
Based on its mechanism of action , BLENREP can cause fetal harm when administered to a pregnant woman , because it contains a genotoxic compound ( the microtubule inhibitor , MMAF ) and it targets actively dividing cells [ see Clinical Pharmacology ( 12.1 ), Nonclinical Toxicology ( 13.1 ) of full Prescribing Information ]. Human immunoglobulin G ( IgG ) is known to cross the placenta ; therefore , belantamab mafodotin-blmf has the potential to be transmitted from the mother to the developing fetus . There are no available data on the use of BLENREP in pregnant women to evaluate for drug-associated risk . No animal reproduction studies were conducted with BLENREP . Advise pregnant women of the potential risk to a fetus .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown . All pregnancies have a background risk of birth defect , loss , or other adverse outcome . In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 % to 4 % and 15 % to 20 %, respectively .
Data
Animal Data : Animal reproductive or developmental toxicity studies were not conducted with belantamab mafodotin-blmf . The cytotoxic component of BLENREP , MMAF , disrupts microtubule function , is genotoxic , and can be toxic to rapidly dividing cells , suggesting it has the potential to cause embryotoxicity and teratogenicity .
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