BLENREP safety profile

Adverse events

Adverse reactions reported in ≥10% of patients (N = 95)1

Adverse reactions BLENREP
N = 95
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
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.

Laboratory abnormalities reported in ≥20% of patients (N = 95)1

Laboratory abnormality

BLENREP
N = 95

All Grades
(%)
Grade 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
  • 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.1
  • 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%).1

Adverse events were managed with supportive care and dose modifications1:

  • Dosage interruptions due to an adverse event occurred in 54% of patients.
    • Adverse reactions resulting in dosage interruptions in >3% of patients included keratopathy (47%), blurred vision (5%), dry eye (3.2%), and pneumonia (3.2%).
  • Dosage 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%).
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Permanent discontinuation due to an adverse reaction occurred in 8% of patients who received BLENREP

The most frequent adverse reaction resulting in permanent discontinuation was keratopathy (2.1%).

Ocular adverse reactions in the pooled safety population

Ocular adverse reactions occurred in 77% of 218 patients in the pooled safety population.1,a

  • Ocular adverse reactions included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%).
    • Among patients with keratopathy (n = 165), 49% of patients had ocular symptoms, 65% had clinically relevant visual acuity changes (decline of 2 or more lines on Snellen Visual Acuity in any eye), and 34% had both ocular symptoms and visual acuity changes.
a
The pooled safety population 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 patients in DREAMM-2. Of these patients,194 received a liquid formulation (not the approved dosage form) rather than the lyophilized powder.

Keratopathy1

Keratopathy of any grade per the Keratopathy and Visual Acuity (KVA) scale (N = 218)

Grade 1 Grade 2 Grade 3 Grade 4
7% 22% 45% 0.5%
  • Onset: Most keratopathy events developed within the first 2 treatment cycles (cumulative incidence of 65% by Cycle 2).
  • Recovery: 39% of the 149 patients with Grade 2-4 keratopathy recovered to Grade 1 or lower after median follow-up of 6.2 months.
    • Of the 61% who had ongoing keratopathy:
      • 28% were still on treatment
      • 9% were in follow-up
      • 24% of follow-up ended due to death, study withdrawal, or being lost to follow-up
    • Median time to resolution: 2 months (range: 11 days to 8.3 months)
    • Median time to resolution: 
      • 2 months (range: 11 days to 8.3 months)
  • Cases of corneal ulcer (ulcerative and infective keratitis) have been reported.

Visual acuity changes1

Changes in visual acuity may be associated with difficulty in driving or reading.

Clinically significant decreases in vision in the better-seeing eye (N = 218)

Worse than 20/40 20/200 or worse
19% 1.4%
88% resolved All patients resolved
Median time to resolution: 22 days
(range: 7 days to 4.2 months)
Median duration: 22 days
(range: 15 to 22 days)
  • No permanent loss of vision was reported in the DREAMM-2 study.²