BLENREP Powder for concentrate for solution for infusion Ref.[50842] Active ingredients: Belantamab mafodotin

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).

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 4.2). 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 4.8). 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 4.8). 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”.

No formal drug interaction studies have been performed with belantamab mafodotin. Based on available in vitro and clinical data, there is a low risk of pharmacokinetic or pharmacodynamic drug interactions for belantamab mafodotin (see section 5.2).

Women of child-bearing potential/Contraception in males and females

Women

The pregnancy status of child-bearing women should be verified prior to initiating therapy with BLENREP.

Women of child-bearing potential should use effective contraception during treatment with BLENREP and for 4 months after the last dose.

Men

Men with female partners of child-bearing potential should use effective contraception during treatment with BLENREP and for 6 months after the last dose.

Pregnancy

There are no data from the use of BLENREP in pregnant women.

Based on the mechanism of action of the cytotoxic component monomethyl auristatin F (MMAF), belantamab mafodotin can cause embryo-foetal harm when administered to a pregnant woman (see section 5.3). Human immunoglobulin G (IgG) is known to cross the placenta; therefore, belantamab mafodotin has the potential to be transmitted from the mother to the developing foetus (see section 5.3).

BLENREP should not be used during pregnancy unless the benefit to the mother outweighs the potential risks to the foetus. If a pregnant woman needs to be treated she should be clearly advised on the potential risk to the foetus.

Breast-feeding

It is not known whether belantamab mafodotin is excreted into human milk. Immunoglobulin G (IgG) is present in human milk in small amounts. Since belantamab mafodotin is a humanised IgG monoclonal antibody, and based on the mechanism of action, it may cause serious adverse reactions in breast-fed children. Women should be advised to discontinue breast-feeding prior to initiating treatment with BLENREP and for 3 months after the last dose.

Fertility

Based on findings in animals and the mechanism of action, belantamab mafodotin may impair fertility in females and males of reproductive potential (see section 5.3).

Therefore, women of childbearing potential who may desire children in the future should be counselled prior to therapy regarding the option of having eggs frozen before treatment. Men being treated with this medicine are advised to have sperm samples frozen and stored before treatment.

BLENREP has a moderate influence on the ability to drive or use machines (see sections 4.4 and 4.8). Patients should be advised to use caution when driving or operating machines as BLENREP may affect their vision.

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:

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 listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.