BLENREP 100 mg: Price Ex-Factory €6.974,48
ABRIDGED SUMMARY OF PRODUCT CHARACTERISTICS ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. Please refer to the Summary of Product Characteristics for a complete information on the use of this product. NAME OF THE MEDICINAL PRODUCT BLENREP 100 mg powder for concentrate for solution for infusion EU/1/20/1474/001 ATC code: L01FX15 QUALITATIVE AND QUANTITATIVE COMPOSITION One vial of powder contains 100 mg of belantamab mafodotin. After reconstitution, the solution contains 50 mg belantamab mafodotin per mL. Belantamab mafodotin is an antibody-drug conjugate that contains belantamab, an afucosylated humanised monoclonal IgG1k antibody specific for B cell maturation antigen (BCMA), produced using recombinant DNA technology in a mammalian cell line (Chinese Hamster Ovary) that is conjugated with maleimidocaproyl monomethyl auristatin F (mcMMAF). THERAPEUTIC INDICATIONS BLENREP is indicated as monotherapy for the treatment of multiple myeloma in adult patients, who have received at least four prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. POSOLOGY AND METHOD OF ADMINISTRATION Treatment with BLENREP should be initiated and supervised by physicians experienced in the treatment of multiple myeloma. Recommended supportive care Patients should have an ophthalmic examination (including visual acuity and slit lamp examination) performed by an eye care professional at baseline, before the subsequent 3 treatment cycles, and as clinically indicated whilst on treatment (see section “Special warnings and precautions for use”). Physicians should advise patients to administer preservative-free artificial tears at least 4 times a day beginning on the first day of infusion and continuing until completion of treatment as this may reduce corneal symptoms (see section “Special warnings and precautions for use”). For patients with dry eye symptoms, additional therapies may be considered as recommended by their eye care professional. Posology The recommended dose is 2.5 mg/kg of BLENREP administered as an intravenous infusion once every 3 weeks. It is recommended that treatment should be continued until disease progression or unacceptable toxicity (see section “Special warnings and precautions for use”). Dose modifications Recommended dose modifications for corneal adverse reactions are provided in Table 1. Table 2 provides dose modifications recommended for other adverse reactions. Management of corneal adverse reactions Corneal adverse reactions may include findings upon eye examination and/or changes in visual acuity (see sections “Special warnings and precautions for use” and “Undesirable effects”). The treating physician should review the patient’s ophthalmic examination report before dosing and should determine the dose of BLENREP based on the highest category from the report in the most severely affected eye as both eyes may not be affected to the same degree (Table 1). During the ophthalmic examination, the eye care professional should assess the following: • The corneal examination finding(s) and the decline in best corrected visual acuity (BCVA). • If there is a decline in BCVA, the relationship of corneal examination findings to BLENREP should be determined. • The highest category grading for these examination findings and BCVA should be reported to the treating physician. Table 1. Dose modifications for corneal adverse reactions Categorya / Eye examination findings / Recommended dose modifications / Mild Corneal examination finding(s) Mild superficial keratopathyb Change in BCVA Decline from baseline of 1 line on Snellen Visual Acuity Continue treatment at current dose. Moderate Corneal examination finding(s) Moderate superficial keratopathyc Change in BCVA Decline from baseline of 2 or 3 lines (and Snellen Visual Acuity not worse than 20/200) Withhold treatment until improvement in examination findings and BCVA to mild severity or better. Consider resuming treatment at a reduced dose of 1.9 mg/kg. Severe Corneal examination finding(s) Severe superficial keratopathyd Corneal epithelial defecte Change in BCVA Decline from baseline of more than 3 lines on Snellen Visual Acuity Withhold until improvement in examination findings and BCVA to mild severity or better. For worsening symptoms that are unresponsive to appropriate management, consider discontinuation. a The severity category is defined by the most severely affected eye as both eyes may not be affected to the same degree. b Mild superficial keratopathy (documented worsening from baseline), with or without symptoms. c Moderate superficial keratopathy – with or without patchy microcyst-like deposits, sub-epithelial haze (peripheral), or a new peripheral stromal opacity. d Severe superficial keratopathy with or without diffuse microcyst-like deposits involving the central cornea, sub-epithelial haze (central), or a new central stromal opacity. e A corneal defect may lead to corneal ulcers. These should be managed promptly and as clinically indicated by an eye care professional. Table 2. Dose modifications for other adverse reactions Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Special populations Elderly No dose adjustment is required for elderly patients (see section 5.2 of the complete SPC). Renal impairment No dose adjustment is required in patients with mild or moderate renal impairment (eGFR ³30 mL/min). There are insufficient data in patients with severe renal impairment to support a dose recommendation (see section 5.2 of the complete SPC). Hepatic impairment No dose adjustment is required in patients with mild hepatic impairment (bilirubin greater than ULN to less than or equal to 1.5 × ULN or aspartate transaminase [AST] greater than ULN). There are insufficient data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment to support a dose recommendation (see section 5.2 of the complete SPC). Body weight BLENREP has not been studied in patients with body weight < 40 kg or > 130 kg (see section 5.2 of the complete SPC). Paediatric population The safety and efficacy of BLENREP in children and adolescents below 18 years of age have not been established. No data are available. Method of administration BLENREP is for intravenous use. BLENREP must be reconstituted and diluted by a healthcare professional prior to administration as an intravenous infusion. BLENREP should be infused over a minimum of 30 minutes (see section 6.6 of the complete SPC). CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the complete SPC. SPECIAL WARNINGS AND PRECAUTIONS FOR USE Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Corneal adverse reactions Corneal adverse reactions have been reported with the use of BLENREP. The most commonly reported adverse reactions were keratopathy or microcyst-like epithelial changes in corneal epithelium (as seen on eye examination) with or without changes in visual acuity, blurred vision, and dry eye symptoms. Patients with a history of dry eyes were more prone to develop changes in the corneal epithelium. Changes in visual acuity may be associated with difficulty in driving or operating machinery (see section 4.7 of the complete SPC). Ophthalmic examinations, including assessment of visual acuity and slit lamp examination, should be performed at baseline, before the subsequent 3 treatment cycles and during treatment as clinically indicated. Patients should be advised to administer preservative-free artificial tears at least 4 times a day during treatment (see section “Posolgy and mode of administration”). Patients should avoid using contact lenses until the end of treatment. Patients experiencing keratopathy with or without changes in visual acuity may require a dose modification (delay and/or reduction) or treatment discontinuation based on severity of findings (see Table 1). Cases of corneal ulcer (ulcerative and infective keratitis) have been reported (see section “Undesirable effects”). These should be managed promptly and as clinically indicated by an eye care professional. Treatment with BLENREP should be interrupted until the corneal ulcer has healed (see Table 1). Thrombocytopenia Thrombocytopenic events (thrombocytopenia and platelet count decreased) were frequently reported in study 205678. Thrombocytopenia may lead to serious bleeding events, including gastrointestinal and intracranial bleeding. Complete blood counts should be obtained at baseline and monitored during treatment, as clinically indicated. Patients experiencing Grade 3 or 4 thrombocytopenia or those on concomitant anticoagulant treatments may require more frequent monitoring and should be managed with a dose delay or dose reduction (see Table 2). Supportive therapy (e.g. platelet transfusions) should be provided according to standard medical practice. Infusion-Related Reactions Infusion-related reactions (IRR) have been reported with BLENREP. Most IRRs were Grade 1-2 and resolved within the same day (see section “Undesirable effects”). If a grade 2 or higher infusion- related reaction occurs during administration, reduce the infusion rate or stop the infusion depending on the severity of the symptoms. Institute appropriate medical treatment and restart infusion at a slower rate, if the patient’s condition is stable. If Grade 2 or higher IRR occurs, administer premedication for subsequent infusions (see Table 2). Pneumonitis Cases of pneumonitis from spontaneous reports and named patient programs, including fatal events, have been observed with BLENREP. Evaluation of patients with new or worsening unexplained pulmonary symptoms (e.g. cough, dyspnea) should be performed to exclude possible pneumonitis. In case of suspected Grade 3 or higher pneumonitis, BLENREP should be withheld. If Grade 3 or higher pneumonitis is confirmed, appropriate treatment should be initiated. BLENREP should only be resumed after an evaluation of the benefit and risk. Excipients This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg dose, that is to say essentially “sodium-free”. 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 (%) Infections and infestations Pneumoniab Very common Any Grade 11 Grade 3-4 7 Upper respiratory tract infection Common Any Grade 9 Grade 3-4 0 Blood and lymphatic system disorders Thrombocytopeniac Very common Any Grade 38 Grade 3-4 22 Anaemia Any Grade 27 Grade 3-4 21 Lymphopeniad Any Grade 20 Grade 3-4 17 Leukopeniae Any Grade 17 Grade 3-4 6 Neutropeniaf Any Grade 15 Grade 3-4 11 Eye disorders Keratopathyg Very common Any Grade 71 Grade 3-4 31 Blurred vision eventsh Any Grade 25 Grade 3-4 4 Dry eye eventsi Any Grade 15 Grade 3-4 1 Photophobia Common Any Grade 4 Grade 3-4 0 Eye irritation Any Grade 3 Grade 3-4 0 Ulcerative keratitis Uncommon Any Grade 1 Grade 3-4 1 Infective keratitis Any Grade 1 Grade 3-4 1 Respiratory, thoracic and mediastinal disorders Pneumonitis Not known Any Grade NA Grade 3-4 NA Gastrointestinal disorders Nausea Very common Any Grade 25 Grade 3-4 0 Diarrhoea Any Grade 13 Grade 3-4 1 Vomiting Common Any Grade 7 Grade 3-4 2 Renal and urinary Disorders Albuminuriak Common Any Grade 2 Grade 3-4 1 General disorders and administration site conditions Pyrexia Very common Any Grade 23 Grade 3-4 4 Fatigue Any Grade 16 Grade 3-4 2 Investigations Increased aspartate aminotransferase Very common Any Grade 21 Grade 3-4 2 Increased gamma glutamyltransferase Any Grade 11 Grade 3-4 3 Increased creatine phosphokinase Common Any Grade 5 Grade 3-4 2 Injury, poisoning and procedural complications Infusion-related reactionsj Very common Any Grade 21 Grade 3-4 3 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 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. k 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: Belgium Federal Agency for Medicines and Health Products Division Vigilance Boîte Postale 97 B-1000 Brussels Madou Website: www.notifieruneffetindesirable.be e-mail: firstname.lastname@example.org Luxembourg Centre Régional de Pharmacovigilance de Nancy Bâtiment de Biologie Moléculaire et de Biopathologie (BBB) CHRU de Nancy – Hôpitaux de Brabois Rue du Morvan 54 511 Vandoeuvre Les Nancy Cedex Tél.: (+33) 3 83 65 60 85 / 87 e-mail : email@example.com ou Direction de la Santé Division de la Pharmacie et des Médicaments 20, rue de Bitbourg L-1273 Luxembourg-Hamm Tél.: (+352) 2478 5592 e-mail: firstname.lastname@example.org Link pour le formulaire : https://guichet.public.lu/fr/entreprises/sectoriel/sante/medecins/notification-effets-indesirables-medicaments.html MARKETING AUTHORISATION HOLDER GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland DATE OF APPROVAL OF THE TEXT 06/2022 (v.07) DELIVERY STATUS Medicinal product subject to medical prescription.