Blenrep Prescribing Information
BLENREP caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes [see Warnings and Precautions ].
Conduct ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms. Withhold BLENREP until improvement and resume, or permanently discontinue, based on severity [see Dosage and Administration , Warnings and Precautions ].
Because of the risk of ocular toxicity, BLENREP is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BLENREP REMS [see Warnings and Precautions ].
BLENREP is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
This indication is approved under accelerated approval based on response rate [see Clinical Studies ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Important Safety Information
Perform an ophthalmic exam prior to initiation of BLENREP and during treatment [see Warnings and Precautions ].
Advise patients to use preservative-free lubricant eye drops and avoid contact lenses unless directed by an ophthalmologist [see Warnings and Precautions ].
Recommended Dosage
The recommended dosage of BLENREP is 2.5 mg/kg of actual body weight given as an intravenous infusion over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.
Dosage Modifications for Adverse Reactions
The recommended dose reduction for adverse reactions is:
- •
- BLENREP 1.9 mg/kg intravenously once every 3 weeks.
Discontinue BLENREP in patients who are unable to tolerate a dose of 1.9 mg/kg (see Tables 1 and 2).
Corneal Adverse Reactions
The recommended dosage modifications for corneal adverse reactions, based on both corneal examination findings and changes in best-corrected visual acuity (BCVA), are provided in Table 1 [see Warnings and Precautions ]. Determine the recommended dosage modification of BLENREP based on the worst finding in the worst affected eye. Worst finding should be based on either a corneal examination finding or a change in visual acuity per the Keratopathy and Visual Acuity (KVA) scale.
| KVA = Keratopathy and Visual Acuity, BCVA = best corrected visual acuity. a Mild superficial keratopathy (documented worsening from baseline), with or without symptoms. b Changes in visual acuity due to treatment-related corneal findings. 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, sub-epithelial haze (central), or a new central stromal opacity. e Corneal epithelial defect such as corneal ulcers. | ||
Corneal Adverse Reaction | Recommended Dosage Modifications | |
Grade 1 | Corneal examination finding(s): Mild superficial keratopathya Change in BCVAb: Decline from baseline of 1 line on Snellen Visual Acuity | Continue treatment at current dose. |
Grade 2 | Corneal examination finding(s): Moderate superficial keratopathyc Change in BCVAb: Decline from baseline of 2 or 3 lines on Snellen Visual Acuity and not worse than 20/200 | Withhold BLENREP until improvement in both corneal examination findings and change in BCVA to Grade 1 or better and resume at same dose. |
Grade 3 | Corneal examination finding(s): Severe superficial keratopathyd Change in BCVAb: Decline from baseline by more than 3 lines on Snellen Visual Acuity and not worse than 20/200 | Withhold BLENREP until improvement in both corneal examination findings and change in BCVA to Grade 1 or better and resume at reduced dose. |
Grade 4 | Corneal examination finding(s): Corneal epithelial defecte Change in BCVAb: Snellen Visual Acuity worse than 20/200 | Consider permanent discontinuation of BLENREP. If continuing treatment, withhold BLENREP until improvement in both corneal examination findings and change in BCVA to Grade 1 or better and resume at reduced dose. |
Other Adverse Reactions
The recommended dosage modifications for other adverse reactions are provided in Table 2.
Adverse Reaction | Severity | Recommended Dosage Modifications |
Thrombocytopenia [see Warnings and Precautions ] | Platelet count 25,000 to less than 50,000/mcL | Consider withholding BLENREP and/or reducing the dose of BLENREP. |
Platelet count less than 25,000/mcL | Withhold BLENREP until platelet count improves to Grade 3 or better. Consider resuming at a reduced dose. | |
Infusion-related reactions [see Warnings and Precautions ] | Grade 2 (moderate) or Grade 3 (severe) | Interrupt infusion and provide supportive care. Once symptoms resolve, resume at lower infusion rate; reduce the infusion rate by at least 50%. |
Grade 4 (life-threatening) | Permanently discontinue BLENREP and provide emergency care. | |
Other Adverse Reactions [see Adverse Reactions ] | Grade 3 | Withhold BLENREP until improvement to Grade 1 or better. Consider resuming at a reduced dose. |
Grade 4 | Consider permanent discontinuation of BLENREP. If continuing treatment, withhold BLENREP until improvement to Grade 1 or better and resume at reduced dose. |
Preparation and Administration
BLENREP is a hazardous drug. Follow applicable special handling and disposal procedures.1
Calculate the dose (mg), total volume (mL) of solution required, and the number of vials of BLENREP needed based on the patient’s actual body weight. More than 1 vial may be needed for a full dose. Do not round down for partial vials.
Reconstitution
- •
- Remove the vial(s) of BLENREP from the refrigerator and allow to stand for approximately 10 minutes to reach room temperature (68°F to 77°F [20°C to 25°C]).
- •
- Reconstitute each 100-mg vial of BLENREP with 2 mL of Sterile Water for Injection, USP, to obtain a final concentration of 50 mg/mL. Gently swirl the vial to aid dissolution. Do not shake.
- •
- If the reconstituted solution is not used immediately, store refrigerated at 36ºF to 46ºF (2ºC to 8ºC) or at room temperature (68°F to 77°F [20°C to 25°C]) for up to 4 hours in the original container. Discard if not diluted within 4 hours. Do not freeze.
- •
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear to opalescent, colorless to yellow to brown liquid. Discard if extraneous particulate matter is observed.
Dilution
- •
- Withdraw the calculated volume of BLENREP from the appropriate number of vials and dilute in a 250-mL infusion bag of 0.9% Sodium Chloride Injection, USP, to a final concentration of 0.2 mg/mL to 2 mg/mL. The infusion bags must be made of polyvinylchloride (PVC) or polyolefin (PO).
- •
- Mix the diluted solution by gentle inversion. Do not shake.
- •
- Discard any unused reconstituted solution of BLENREP left in the vial(s).
- •
- If the diluted infusion solution is not used immediately, store refrigerated at 36ºF to 46ºF (2ºC to 8ºC) for up to 24 hours. Do not freeze. Once removed from refrigeration, administer the diluted infusion solution of BLENREP within 6 hours (including infusion time).
- •
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The diluted infusion solution should be clear and colorless. Discard if particulate matter is observed.
Administration
- •
- If refrigerated, allow the diluted infusion solution to equilibrate to room temperature (68ºF to 77ºF [20ºC to 25ºC]) prior to administration. Diluted infusion solution may be kept at room temperature for no more than 6 hours (including infusion time).
- •
- Administer by intravenous infusion over approximately 30 minutes using an infusion set made of polyvinyl chloride (PVC) or polyolefin (PO).
- •
- Filtration of the diluted solution is not required; however, if the diluted solution is filtered, use a polyethersulfone (PES)-based filter (0.2 micron).
Do not mix or administer BLENREP as an infusion with other products. The product does not contain a preservative.
For injection: 100 mg of belantamab mafodotin-blmf as a white to yellow lyophilized powder in a single-dose vial for reconstitution and further dilution.
Pregnancy
Risk Summary
Based on its mechanism of action, BLENREP can cause fetal harm when administered to a pregnant woman, because it contains a genotoxic compound (the microtubule inhibitor, MMAF) and it targets actively dividing cells [see Clinical Pharmacology , Nonclinical Toxicology ]. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, belantamab mafodotin-blmf has the potential to be transmitted from the mother to the developing fetus. There are no available data on the use of BLENREP in pregnant women to evaluate for drug-associated risk. No animal reproduction studies were conducted with BLENREP. Advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcome. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data: Animal reproductive or developmental toxicity studies were not conducted with belantamab mafodotin-blmf. The cytotoxic component of BLENREP, MMAF, disrupts microtubule function, is genotoxic, and can be toxic to rapidly dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
Lactation
Risk Summary
There is no data on the presence of belantamab mafodotin-blmf in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with BLENREP and for 3 months after the last dose.
Females and Males of Reproductive Potential
BLENREP can cause fetal harm when administered to pregnant women [see Use in Specific Populations ].
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to initiating BLENREP.
Contraception
Females: Advise women of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.
Males: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with BLENREP and for 6 months after the last dose [see Nonclinical Toxicology ].
Infertility
Based on findings in animal studies, BLENREP may impair fertility in females and males. The effects were not reversible in male rats, but were reversible in female rats [see Nonclinical Toxicology ].
Pediatric Use
The safety and effectiveness of BLENREP in pediatric patients have not been established.
Geriatric Use
Of the 218 patients who received BLENREP in DREAMM-2, 43% were aged 65 to less than 75 years and 17% were aged 75 years and older. Clinical studies of BLENREP did not include sufficient numbers of patients aged 65 and older to determine whether the effectiveness differs compared with that of younger patients. Keratopathy occurred in 80% of patients aged less than 65 years and 73% of patients aged 65 years and older. Among the patients who received BLENREP at the 2.5-mg/kg dose in DREAMM-2 (n = 95), keratopathy occurred in 67% of patients aged less than 65 years and 73% of patients aged 65 years and older. Clinical studies did not include sufficient numbers of patients 75 years and older to determine whether they respond differently compared with younger patients.
Renal Impairment
No dose adjustment is recommended for patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30 to 89 mL/min/1.73m2 as estimated by the Modification of Diet in Renal Disease [MDRD] equation) [see Clinical Pharmacology ].
The recommended dosage has not been established in patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2) or end-stage renal disease (ESRD) with eGFR <15 mL/min/1.73 m2 not on dialysis or requiring dialysis [see Clinical Pharmacology ].
Hepatic Impairment
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤upper limit of normal [ULN] and aspartate aminotransferase (AST) >ULN or total bilirubin 1 to ≤1.5 × ULN and any AST).
The recommended dosage of BLENREP has not been established in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN and any AST) [see Clinical Pharmacology ].
None.