BLENREP safety profile

Adverse events

  • Adverse reactions

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

    Adverse reactions

    BLENREP
    N = 95

    All Grades
    (%)

    Grades 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

  • 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 reaction occurred in 54% of patients.

    • Adverse reactions resulting in dosage interruptions occurred 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%).

  • No permanent, complete loss of vision was reported in the DREAMM-2 study.2

At 6 months, 8% of patients treated with BLENREP had permanently discontinued due to an adverse reaction. Keratopathy was the most frequent adverse reaction to cause discontinuation at 2.1%.1

The safety data at the 13-month follow-up further establishes the safety profile observed at 6 months.3

Ocular adverse reactions in the pooled safety population

Pooled data at 6 months (N = 218)
Ocular adverse reactions occurred in 77% of 218 patients in the pooled safety population.1*
  • 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)

    • 34% had both ocular symptoms and visual acuity changes

At 6 months, in the 2.5-mg/kg cohort, 8% of patients treated with BLENREP had permanently discontinued due to an adverse event.

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

No permanent, complete loss of vision was reported in the DREAMM-2 study.2

  • Keratopathy Incidence, Onset, Resolution

    Keratopathy was the most common adverse event (pooled 6-month data)1

    Incidence

    Overall:
    76%

    Grade 1:
    7%

    Grade 2:
    22%

    Grade 3:
    45%

    Grade 4:
    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

    • In 24%, the 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).

    • Cases of corneal ulcer (ulcerative and infective keratitis) have been reported.

  • Changes in Visual Acuity Incidence and Resolution

    Changes in visual acuity are shown by incidence, onset, recovery, and median time to resolution (pooled 6-month data)1
     

    Worse than 20/40

    20/200 or worse

    Incidence

    19%

    1.4%

    Recovery

    88% resolved

    100% resolved

    Median time to resolution*

    22 days (range: 7 days to 4.2 months)

    22 days (range: 15 to 22 days)

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

    • No permanent loss of vision was reported in the DREAMM-2 study.2,4

At the 13-month follow-up, in the 2.5-mg/kg cohort (N = 95)4
  • 72% of patients experienced keratopathy

  • 56% of patients had ocular symptoms and/or visual acuity changes3

    • Symptoms included those such as blurred vision and dry eye. Visual acuity change was at least 2 lines on Snellen Visual Acuity in the better-seeing eye

      • 18% of patients experienced a change in BCVA to worse than 20/40*

      • 1% of patients experienced a change in BCVA to 20/200 or worse

9% of patients treated with BLENREP 2.5 mg/kg discontinued due to an adverse event.3

  • Of these patients, 3% discontinued treatment due to corneal events

    • keratopathy (1%)

    • changes in visual acuity (1%)

    • blurred vision (1%)

No permanent, complete loss of vision was reported in the DREAMM-2 study.2,4

  • Keratopathy Incidence, Onset, Resolution

    At 13-month follow-up, median time to resolution of keratopathy was 86.5 days4

    Incidencea

    Overall:
    72%

    Grade 1:
    8%

    Grade 2:
    17%

    Grade 3:
    45%

    Grade 4:
    1%

    Median time to onset

    37.0 days (range: 19-143 days)b with a majority (69%) of patients experiencing their first event by Dose 4

    Recoveryc

    77% (46/60) recovered from their first event (≥Grade 2)


    48% (29/60) recovered from their last event at last follow-up (≥Grade 2)


    • Among the 31 patients who did not recover from their last event, 9 patients were still receiving treatment, 5 were in follow-up, and 17 did not complete follow-up.3

    Median time to resolution*

    86.5 days (range: 8-358 days)b in all patients, including those with and those without dose modifications

  • Changes in Visual Acuity Incidence, Onset, Resolution

    At 13-month follow-up, median time to resolution for visual acuity adverse events was 22 days4
     

    Worse than 20/40a,b

    20/200 or worsec

    Incidence

    18% (17/95)

    1% (1/95)

    Onset

    66.0 days (range: 20 to 442 days)

    21.0 days (range: 21 to 21 days)

    Recovery

    82% (14/17) resolvedd

    100% resolvede

    Median time to resolution*

    21.5 days (range: 7 to 64 days)

    22.0 days (range: 22 to 22 days)