Blenrep

— THERAPEUTIC DISORDERS TREATED —
  • Leukemias, lymphomas, and other hematologic cancers

Blenrep Generic Name & Formulations

General Description

Belantamab mafodotin-blmf 100mg; per vial; lyophilized pwd for IV infusion after reconstitution and dilution; preservative-free.

Pharmacological Class

BCMA-directed antibody + microtubule inhibitor conjugate.

How Supplied

Single-dose vial—1 (for compassionate use only)

How Supplied

Blenrep for injection is a sterile, preservative-free, white to yellow lyophilized powder for reconstitution and further dilution prior to intravenous use.

Blenrep is supplied in a carton containing one 100-mg single-dose vial with a rubber stopper (not made with natural rubber latex) and aluminum overseal with removable cap (NDC 0173­ 0896-01).

Storage

Store vials refrigerated at 36ºF to 46ºF (2ºC to 8ºC).

Manufacturer

Generic Availability

NO

Blenrep Indications

Indications

In 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.

Blenrep Dosage and Administration

Prior to Treatment Evaluations

Perform an ophthalmic exam prior to initiation of Blenrep and during treatment.

Adult

Give by IV infusion over ~30mins. 2.5mg/kg (of actual body wt.) once every 3 weeks until disease progression or unacceptable toxicity. Dose modifications for adverse reactions: see full labeling.

Children

Not established.

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).

The recommended dosage has not been established in patients with severe renal impairment (eGFR 15 to 29mL/min/1.73m2 ) or end-stage renal disease (ESRD) with eGFR <15mL/min/1.73m2 not on dialysis or requiring dialysis.

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).

 

Other Modifications

Females and Males of Reproductive Potential

  • Pregnancy testing is recommended for females of reproductive potential prior to initiating Blenrep.

  • Advise women of reproductive potential to use effective contraception during treatment and for 4 months after the last dose. 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. 

  • 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.

Blenrep Contraindications

Not Applicable

Blenrep Boxed Warnings

Boxed Warning

Ocular toxicity.

Boxed Warning

Ocular Toxicity

  • 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.

  • 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.

  • 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.

Blenrep Warnings/Precautions

Warnings/Precautions

Risk of ocular toxicity. Conduct ophthalmic exams at baseline (within 3 weeks prior to first dose), prior to each subsequent dose, and for worsening symptoms (perform each follow-up exam at least 1 week after the previous dose and within 2 weeks prior to the next dose). Withhold therapy until improvement; resume or permanently discontinue based on severity. Thrombocytopenia: obtain CBCs at baseline and during treatment as clinically indicated; withhold and/or reduce dose based on severity. Monitor for infusion-related reactions; interrupt therapy for Grade 2 or 3 reactions; discontinue if life-threatening reactions occur. Advise use of preservative-free lubricant eye drops at least 4 times daily. Avoid contact lenses (unless directed by an ophthalmologist). Severe renal impairment (eGFR 15–29mL/min/1.73m2) or ESRD (eGFR <15mL/min/1.73m2) not on dialysis or requiring dialysis. Moderate or severe hepatic impairment (total bilirubin >1.5×ULN and any AST). Embryo-fetal toxicity. Advise to use effective contraception during and for 4 months (females of reproductive potential) or 6 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 3 months after the last dose).

Warnings/Precautions

Ocular Toxicity

  • Ocular adverse reactions included keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%).

  • Most keratopathy events developed within the first 2 treatment cycles (cumulative incidence of 65% by Cycle 2). For patients in whom events resolved, the median time to resolution was 2 months (range: 11 days to 8.3 months).

  • Conduct ophthalmic examinations (visual acuity and slit lamp) at baseline, prior to each dose, and promptly for worsening symptoms. Perform baseline examinations within 3 weeks prior to the first dose. Perform each follow-up examination at least 1 week after the previous dose and within 2 weeks prior to the next dose. Withhold Blenrep until improvement and resume at same or reduced dose or consider permanently discontinuing based on severity.

  • Advise patients to use preservative-free lubricant eye drops at least 4 times a day starting with the first infusion and continuing until end of treatment. Avoid use of contact lenses unless directed by an ophthalmologist.

  • Changes in visual acuity may be associated with difficulty for driving and reading. Advise patients to use caution when driving or operating machinery. 

Thrombocytopenia

  • Perform complete blood cell counts at baseline and during treatment as clinically indicated. Consider withholding and/or reducing the dose based on severity.

Infusion-Related Reactions

  • Monitor patients for infusion-related reactions. For Grade 2 or 3 reactions, interrupt the infusion and provide supportive treatment. Once symptoms resolve, resume at a lower infusion rate. Administer premedication for all subsequent infusions. 

  • Discontinue Blenrep for life-threatening infusion-related reactions and provide appropriate emergency care.

Embryo-Fetal Toxicity

  • Advise pregnant women of the potential risk to a fetus. 

  • Advise females of reproductive potential to use effective contraception during treatment with Blenrep and for 4 months after the last dose. 

  • Advise males with female partners of reproductive potential to use effective contraception during treatment with Blenrep and for 6 months after the last dose.

Pregnancy Considerations

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. 

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.

Nursing Mother Considerations

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.

Pediatric Considerations

Safety and effectiveness of Blenrep in pediatric patients have not been established.

Geriatric Considerations

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. 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 Considerations

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).

The recommended dosage has not been established in patients with severe renal impairment (eGFR 15 to 29mL/min/1.73m2 ) or end-stage renal disease (ESRD) with eGFR <15mL/min/1.73m2 not on dialysis or requiring dialysis.

Hepatic Impairment Considerations

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).

 

Other Considerations for Specific Populations

Females and Males of Reproductive Potential

  • Pregnancy testing is recommended for females of reproductive potential prior to initiating Blenrep.

  • Advise women of reproductive potential to use effective contraception during treatment and for 4 months after the last dose. 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. 

  • 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.

REMS

YES

Blenrep Pharmacokinetics

Distribution

The mean steady-state volume of distribution of belantamab mafodotin-blmf was 11 L (15%).

Metabolism

The monoclonal antibody portion of belantamab mafodotin-blmf is expected to be metabolized into small peptides and individual amino acids by catabolic pathways. In vitro, cys-mcMMAF is mainly hydrolyzed and dehydrated to a cyclized isomeric form of cys-mcMMAF.

Elimination

Half-life: 12 days (after the first dose); 14 days (at steady state).

Elimination

Total plasma clearance (mean [CV%]) of belantamab mafodotin-blmf was ~22% lower at steady state (0.7 L/day [50%]) than after the first dose (0.9 L/day [42%]). The terminal phase half-life of belantamab mafodotin-blmf was 12 days after the first dose and 14 days at steady state.

Blenrep Interactions

Blenrep Adverse Reactions

Adverse Reactions

Keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, fatigue; Grade 3 or 4 lab abnormalities (decreased platelets, decreased lymphocytes, decreased hemoglobin, decreased neutrophils, increased creatinine, increased gamma-glutamyl transferase).

Blenrep Clinical Trials

Clinical Trials

The efficacy of Blenrep was evaluated in the open-label, multicenter DREAMM-2 study (NCT03525678) in 97 patients with relapsed or refractory multiple myeloma who had previously received 3 or more prior therapies, including an anti-CD38 monoclonal antibody, and were refractory to an immunomodulatory agent and a proteasome inhibitor.

Patients received either Blenrep 2.5mg/kg or 3.4mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate as evaluated by an Independent Review Committee (IRC) based on the IMWG Uniform Response Criteria for Multiple Myeloma. Only the results of the recommended dosage of 2.5 mg/kg are described below.

Findings showed an ORR in the 2.5mg/kg cohort of 31% (n=30; 97.5% CI, 21-43); 2 patients had a stringent complete response, 1 patient had a complete response, 15 patients had very good partial response, and 12 had a partial response. The median time to first response was 1.4 months (95% CI, 1.0-1.6). The median duration of response (DoR) had not yet been reached at the 6-month analysis, but 73% of responders had a DoR ≥6 months. 

Blenrep Note

Notes

For compassionate use only. Must transition patients currently receiving Blenrep to a compassionate use program to continue treatment. 

For further information or questions, contact GSK Response Center at (877) 768-0092.

For more information related to the Blenrep REMS, please visit www.BlenrepREMS.com or call (855) 209-9188.

Blenrep Patient Counseling

Patient Counseling

Ocular Toxicity

  • Advise patients that ocular toxicity may occur during treatment with Blenrep. Advise patients to administer preservative-free lubricant eye drops as recommended during treatment and to avoid wearing contact lenses during treatment unless directed by a healthcare professional. Advise patients to use caution when driving or operating machinery as Blenrep may adversely affect their vision.

Thrombocytopenia

  • Advise patients to inform their healthcare provider if they develop signs or symptoms of bleeding.

Infusion-Related Reactions 

  • Advise patients to immediately report any signs and symptoms of infusion-related reactions to their healthcare provider.

Embryo-Fetal Toxicity 

  • Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy. 

  • Advise women of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose. 

  • Advise males with female partners of reproductive potential to use effective contraception during treatment with Blenrep and for 6 months after the last dose.

Lactation

  • Advise women not to breastfeed during treatment with Blenrep and for 3 months after the last dose. 

Infertility

  • Advise males and females of reproductive potential that Blenrep may impair fertility.

Pneumonitis

  • Advise patients to immediately report any new or worsening unexplained pulmonary signs or symptoms to their healthcare provider.

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