Initial US Approval:
2025
Key Clinical Studies:
LINKER-MM1 (NCT03761108)
Drug Class/Description:
Bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
See full prescribing information for complete boxed warning.
- Cytokine release syndrome (CRS), including serious or lifethreatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue based on severity.
- Neurologic Toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves and modify the next dose or permanently discontinue based on severity.
- LYNOZYFIC is available only through a restricted program called the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS).
Indications and Usage:
LYNOZYFIC is a bispecific B-cell maturation antigen (BCMA)‑directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti‑CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Dosage and Administration:
- Premedicate to reduce the risk of CRS and infusion-related reactions (IRR).
- Administer only as an intravenous infusion.
- Recommended Dosage:
| Dosing Schedule | Day | Step | Dose of LYNOZYFIC |
|---|---|---|---|
| Step-Up Dosing Schedule |
Day 1 |
Step-up dose 1 | 5 mg |
|
Day 8 |
Step-up dose 2 | 25 mg | |
|
Day 15 |
First treatment dose | 200 mg | |
| Weekly Dosing Schedule |
One week after Day 15 treatment dose and once weekly from Week 4 to Week 13 for 10 treatment doses |
Second and subsequent treatment doses | 200 mg |
| Biweekly (Every 2 Weeks) Dosing Schedule |
Week 14 and every 2 weeks thereafter |
Subsequent treatment doses | 200 mg |
| Patients who have achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg | |||
| Every 4 Weeks Dosing Schedule |
At Week 24 or after and every 4 weeks thereafter |
Subsequent treatment doses | 200 mg |
- Patients should be hospitalized for 24 hours after administration of the first step-up dose and for 24 hours after administration of the second step-up dose.
- See Full Prescribing Information for instructions on preparation and administration.
Dosage Forms and Strengths:
Injection:
- 5 mg/2.5 mL (2 mg/mL) single-dose vial
- 200 mg/10 mL (20 mg/mL) single-dose vial
Contraindications:
None.
Warnings and Precautions:
- Infections: Can cause serious or fatal infections. Monitor patients for signs or symptoms of infection and treat accordingly.
- Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment.
- Hepatotoxicity: Can cause hepatotoxicity. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.
- Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.
Adverse Reactions:
The most common adverse reactions (≥20%) are musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea.
The most common Grade 3 or 4 laboratory abnormalities (≥30%) are decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count.
Use in Specific Populations:
Lactation: Advise not to breastfeed.
Adapted From:
https://www.regeneron.com/downloads/lynozyfic_fpi.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
