Summary of the safety profile The most common adverse reactions (any grade) were corneal examination findings (including keratopathy) (84%), visual acuity reduced (81%), thrombocytopenia (62%), vision blurred (52%), dry eye (36%), foreign body sensation in eyes (32%), photophobia (30%), eye irritation (28%), neutropenia (27%), anaemia (23%), diarrhoea (23%), neuropathies (23%), and eye pain (21%).
The most common serious adverse reactions (any grade) were pneumonia (9%), pyrexia (4%), COVID-19 (3%), COVID-19 pneumonia (3%), and thrombocytopenia (2%). The proportion of subjects with treatment discontinuation due to adverse reactions was 24%.
The most common adverse reaction leading to treatment discontinuation was ocular events (7%). The frequency of dose reduction due to adverse reactions was 63%. The most common adverse reactions leading to dose reduction were ocular events (39%), thrombocytopenia (12%), platelet count 11 decreased (6%), insomnia (5%), peripheral sensory neuropathy (5%), neuropathy peripheral (5%), neutropenia (4%), fatigue (3%), and neutrophil count decreased (2%).
The frequency of dose delay due to adverse reactions was 83%. The most common adverse reactions leading to dose delay were ocular events (67%), thrombocytopenia (16%), COVID-19 (11%), platelet count decreased (8%), neutropenia (8%), upper respiratory tract infection (7%), pneumonia (7%), diarrhoea (4%), pyrexia (4%), neutrophil count decreased (4%), peripheral sensory neuropathy (4%), bronchitis (3%), COVID-19 pneumonia (3%), cataract (3%), neuropathy peripheral (3%), and alanine aminotransferase increased (3%).
Tabulated list of adverse reactions The adverse reaction frequencies are based on all-cause adverse event frequencies, from patients with multiple myeloma exposed to belantamab mafodotin, for which, after thorough assessment, a causal relationship between the medicinal product and the adverse event is at least a reasonable possibility.
The safety of belantamab mafodotin has been evaluated in more than 7500 patients with multiple myeloma, including 516 patients who received belantamab mafodotin in triplet combinations as part of the DREAMM-6 (a Phase 1/2, open-label dose exploration study), DREAMM-7, and DREAMM-8 studies, 312 patients who received belantamab mafodotin as monotherapy in the DREAMM-2 and DREAMM-3 studies, and including patients from the post-marketing setting.
Adverse reactions are listed in Table 4 by system organ class and by frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Frequencies are defined as:
Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1 000 to <1/100 Rare: ≥1/10 000 to <1/1 000 Very rare: <1/10 000 Not known: frequency cannot be estimated from the available data Table 4: Adverse reactions in multiple myeloma patients treated with belantamab mafodotin in clinical trials and post-marketing System organ class (SOC) Adverse reaction Frequency Incidence (%) Any grade Grade 3-4 Infections and infestations COVID-19 Very common 18 3 Upper respiratory tract infection Very common 15 <1 Pneumonia Very common 13 7 Urinary tract infection Common 9 2 Bronchitis Common 5 ˂1 COVID-19 pneumonia Common 3 2 Hepatitis B reactivation Uncommon <1 <1 Blood and lymphatic system disorders Thrombocytopeniaa Very common 62 47 Neutropeniab Very common 27 22 Anaemia Very common 23 12 Lymphopeniac Very common 10 7 Leukopeniad Common 9 4 Febrile neutropenia Common 1 1 12 System organ class (SOC) Adverse reaction Frequency Incidence (%) Any grade Grade 3-4 Immune system disorders Hypogammaglobulinemia Common 2 ˂1 Metabolism and nutrition disorders Decreased appetite Common 8 <1 Psychiatric disorders Insomnia Very Common 13 1 Nervous system disorders Neuropathiese Very common 23 2 Eye disorders Corneal examination findings (including keratopathy)f,g Very common 84 62 Visual acuity reducedf Very common 81 50 Vision blurred Very common 52 13 Dry eye Very common 36 5 Foreign body sensation in eyes Very common 32 2 Photophobia Very common 30 1 Eye irritation Very common 28 3 Eye pain Very common 21 <1 Cataract Very common 13 4 Visual impairment Common 8 5 Lacrimation increased Common 5 <1 Diplopia Common 3 <1 Eye pruritus Common 2 <1 Ocular discomfort Common 1 <1 Corneal ulcerh Common 1 <1 Corneal hypoesthesia Not known - - Respiratory, thoracic and mediastinal disorders Cough Very common 11 ˂1 Dyspnoea Common 9 1 Pneumonitis Uncommon <1 <1 Gastrointestinal disorders Diarrhoea Very common 23 2 Nausea Very common 17 <1 Constipation Very common 15 <1 Vomiting Common 7 <1 Hepatobiliary Disorders Increased aspartate aminotransferase Very common 15 2 Increased alanine aminotransferase Very common 13 3 Increased gamma glutamyltransferase Very common 11 5 Porto-sinusoidal vascular disorderi Uncommon <1 <1 Skin and subcutaneous tissue disorders Rash Common 4 <1 Musculoskeletal Arthralgia Very common 11 <1 13 System organ class (SOC) Adverse reaction Frequency Incidence (%) Any grade Grade 3-4 and connective tissue disorders Back pain Very common 11 1 Increased creatine phosphokinase Common 3 1 Renal and urinary disorders Albuminuriaj Common 3 <1 General disorders and administration site conditions Fatigue Very common 19 3 Pyrexia Very common 18 <1 Asthenia Common 6 1 Injury, poisoning and procedural complications Infusion-related reactionsk Very Common 11 <1 a Includes thrombocytopenia and platelet count decreased.
b Includes neutropenia and neutrophil count decreased. c Includes lymphopenia and lymphocyte count decreased. d Includes leukopenia and white blood cell count decreased. e Includes peripheral sensory neuropathy, neuropathy peripheral, neuralgia, polyneuropathy, peripheral motor neuropathy, sensory loss, peripheral sensorimotor neuropathy.
f Based on ophthalmic examination findings. g Includes superficial punctate keratopathy, microcyst-like epithelial changes, stippled vortex staining pattern, sub-epithelial haze, corneal epithelial […]