Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The safety of BLENREP was evaluated in 95 patients who received BLENREP 2.5 mg/kg in study 205678. The most frequent adverse reactions (≥30%) were keratopathy (71%) and thrombocytopenia
(38%). The most commonly reported serious adverse reactions were pneumonia (7%), pyrexia (7%) and IRRs (3%). Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received BLENREP with 3% related to ocular adverse reactions.

Tabulated list of adverse reactions

Table 3 summarises adverse drug reactions that occurred in patients receiving the recommended dose of BLENREP 2.5 mg/kg once every 3 weeks.

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) and not known (cannot be estimated from the available data). Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness.

Table 3. Adverse reactions reported in multiple myeloma patients treated with BLENREP System Organ Class      Adverse reactionsa                     Frequency        Incidence (%) Any     Grade
Grade       3-4 b
Infections and          Pneumonia                             Very common         11        7 infestations            Upper respiratory tract infection        Common           9         0 Blood and lymphatic        Thrombocytopeniac                       Very common          38         22 system disorders           Anaemia                                                      27         21 d
Lymphopenia                                                  20         17 e
Leukopenia                                                   17         6 Neutropeniaf                                                 15         11 
Eye disorders               Keratopathyg                            Very common         71         31 h
Blurred vision events                                       25          4 i
Dry eye events                                              15          1 Photophobia                               Common             4          0 Eye irritation                                               3          0 Ulcerative keratitis                     Uncommon            1          1 Infective keratitis                                          1          1 j
Corneal hypoesthesia                     Not known          NA         NA Respiratory, thoracic and pneumonitis                                Not known          NA         NA mediastinal disorders
Gastrointestinal          Nausea                                    Very common         25          0 disorders                 Diarrhoea                                                     13          1 Vomiting                                  Common             7          2 l
Renal and urinary           Albuminuria                               Common             2          1 Disorders
General disorders and       Pyrexia                                 Very common         23          4 administration site conditions                  Fatigue                                                     16          2 
Investigations              Increased aspartate aminotransferase    Very common         21          2 Increased gamma glutamyltransferase                         11          3 Increased creatine phosphokinase          Common            5           2 Injury, poisoning and       Infusion-related reactionsk             Very common         21          3 procedural complications
NA = not applicable a
Adverse reactions coded using MedDRA and graded for severity based CTCAE v4.03.
b
Includes pneumonia and herpes simplex pneumonia c
Includes thrombocytopenia and decreased platelet count.
d
Includes lymphopenia and decreased lymphocyte count.
e
Includes leukopenia and decreased leukocyte count.
f
Includes neutropenia and decreased neutrophil count.
g
Based on eye examination, characterised as corneal epithelium changes with or without symptoms.
h
Includes diplopia, vision blurred, visual acuity reduced, and visual impairment.
i
Includes dry eye, ocular discomfort, and eye pruritus.
j
Preferred term is hypoaesthesia eye.
k
Includes events determined by investigators to be related to infusion. Infusion reactions may include, but are not limited to, pyrexia, chills, diarrhea, nausea, asthenia, hypertension, lethargy, tachycardia.
l
Identified from patients across the BLENREP clinical program including study 205678. The frequency is based on the program-wide exposure.

Description of selected adverse reactions

Corneal adverse reactions
Corneal adverse reactions were assessed in Study 205678 from the safety population (n = 218) which included patients treated with 2.5 mg/kg (n=95). Eye disorder events occurred in 74% patients and the most common adverse reactions were keratopathy or microcyst-like epithelial changes in corneal epithelium [identified on eye exam, with or without symptoms] (71%), blurred vision (25%), and dry eye symptoms (15%). Decreased vision (Snellen Visual Acuity worse than 20/50) in the better eye was reported in 18% and severe vision loss (20/200 or worse) in the better seeing eye was reported in 1% of patients treated with belantamab mafodotin.
The median time to onset of Grade 2 or above corneal findings (best corrected visual acuity or keratopathy on eye examination) was 36 days (range: 19 to 143 days). The median time to resolution of these corneal findings was 91 days (range: 21 to 201 days).
Corneal findings (keratopathy) led to dose delays in 47% of patients, and dose reductions in 27% of patients. Three percent of patients discontinued treatment due to ocular events.

Infusion-related reactions

In clinical studies, the incidence of infusion-related reactions (IRR) with belantamab mafodotin 2.5 mg/kg was 21%, and most (90%) occurred during the first infusion. Most IRRs were reported as
Grade 1 (6%) and Grade 2 (12%) while 3% experienced Grade 3 IRRs. Serious IRRs were reported by 4% of patients and included symptoms of pyrexia and lethargy. Median time to onset and the median duration of the first occurrence of an IRR was 1 day. One patient (1%) discontinued treatment due to IRRs, experiencing Grade 3 IRRs at first and second infusion. No Grade 4 or 5 IRRs were reported.

Thrombocytopenia

Thrombocytopenic events, (thrombocytopenia and platelet count decreased) occurred in 38% of patients treated with belantamab mafodotin 2.5 mg/kg. Grade 2 thrombocytopenic events occurred in 3% of patients, Grade 3 in 9%, and Grade 4 in 13%. Grade 3 bleeding events occurred in 2% of patients and no Grade 4 or 5 events were reported.

Infections

Upper respiratory tract infections were commonly reported across the belantamab mafodotin clinical programme and were mostly mild to moderate (Grade 1 to 3), occurring in 9% of patients treated with belantamab mafodotin 2.5 mg/kg. There were no SAEs of upper respiratory tract infections reported.
Pneumonia was the most frequent infection reported in 11% of patients treated with belantamab mafodotin 2.5 mg/kg. Pneumonia was also the most frequent SAE, reported in 7% of patients.
Infections with a fatal outcome were primarily due to pneumonia (1%).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/.
Additionally, you should also report to GSK Israel (il.safety@gsk.com).