WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME1 See full prescribing information for complete boxed warning. 1
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Lynozyfic®
REMS: FDA approved a REMS for linvoseltamab-gcpt to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of linvoseltamab-gcpt and consists of the following: communication plan, elements to assure safe use, and implementation system. See the FDA REMS page ([Web]). |
Linvoseltamab-gcpt, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is an antineoplastic agent.1
Linvoseltamab-gcpt has the following uses:
Linvoseltamab-gcpt is 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.1
This indication is approved under accelerated approval based on response rate and durability of response.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).1
Linvoseltamab-gcpt is available in the following dosage form(s) and strength(s):
Injection:1
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosing Schedule | Dose of Linvoseltamab-gcpt |
|---|---|
Step-Up Dosing Schedule Day 1 (step-up dose 1) | 5 mg |
Step-Up Dosing Schedule Day 8 (step-up dose 2) | 25 mg |
Step-Up Dosing Schedule Day 15 (first treatment dose) | 200 mg |
Weekly Dosing Schedule (subsequent treatment doses) | 200 mg administered 1 week after first treatment dose and once weekly thereafter from weeks 4-13 for 10 treatment doses |
Biweekly (Every 2 Weeks) Dosing Schedule (subsequent treatment doses) | 200 mg administered at week 14 and every 2 weeks thereafter |
Patients who have achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg | Dose of Linvoseltamab-gcpt |
Every 4 Weeks Dosing Schedule | 200 mg administered at week 24 or after, and then every 4 weeks thereafter |
None.1
Cytokine Release Syndrome (CRS)
Linvoseltamab-gcpt can cause cytokine release syndrome (CRS), which can be serious or life-threatening.1
In the LINKER-MM1 study, CRS occurred in 46% (54/117) of patients who received linvoseltamab-gcpt at the recommended dose, with Grade 1 CRS occurring in 35% (41/117) of patients, Grade 2 in 10% (12/117), and Grade 3 in 0.9% (1/117).1 Thirty-eight percent (45/117) of patients had CRS following step-up dose 1, including 1 patient who experienced Grade 3 CRS; 8% (9/117) had an initial CRS event following a subsequent dose.1 Seventeen percent (19/113) of patients developed CRS after step-up dose 2, 10% (11/111) developed CRS after the first full 200 mg dose of linvoseltamab-gcpt, and 3.6% (4/110) developed CRS after the second full dose.1 Recurrent CRS occurred in 20% (23/117) of patients.1 The median time to onset of CRS from the end of infusion was 11 (range: -1 to 184) hours after the most recent dose with a median duration of 15 (range: 1 to 76) hours.1
Clinical signs and symptoms of CRS included, but were not limited to pyrexia, chills, hypoxia, tachycardia, and hypotension.1
Administer pretreatment medications and initiate therapy according to linvoseltamab-gcpt step-up dosing to reduce the incidence and severity of CRS. 1
Monitor patients for signs and symptoms of CRS after infusion.1 Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur.1
At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold linvoseltamab-gcpt until CRS resolves and modify the next dose or permanently discontinue linvoseltamab-gcpt based on severity. 1
Infusion-related reactions (IRR) may be clinically indistinguishable from manifestations of CRS.1 In the patients who were treated with the recommended step-up dosing regimen and pretreatment medications, the rate of IRR was 9% [11/117 including Grade 2 IRR (4.3%) and Grade 3 IRR (1.7%)].1 For IRR, interrupt or slow the rate of infusion or permanently discontinue linvoseltamab-gcpt based on severity of reaction.1
Linvoseltamab-gcpt is available only through a restricted program under a REMS.1
Neurologic Toxicity, Including Immune Effector Cell-associated Neurotoxicity Syndrome
Linvoseltamab-gcpt can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). 1
In LINKER-MM1, neurologic toxicity occurred in 54% of patients, with Grade 3 or 4 neurologic toxicity occurring in 8%, at the recommended dose.1 Neurologic toxicities included ICANS, depressed level of consciousness, encephalopathy, and toxic encephalopathy.1
ICANS occurred in 8% of patients who received linvoseltamab-gcpt with the recommended dosing regimen, including Grade 3 events in 2.6%.1 Most patients experienced ICANS following step-up dose 1 (5%).1 Two patients (1.8%) experienced initial ICANS following step-up dose 2 and one patient developed the first occurrence of ICANS following a subsequent full dose of linvoseltamab-gcpt.1 Recurrent ICANS occurred in one patient.1 The median time to onset of ICANS was 1 (range: 1 to 4) day after the most recent dose with a median duration of 2 (range: 1 to 11) days.1 The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.1
The most common clinical signs and symptoms of ICANS are confusion, depressed level of consciousness, and lethargy.1 Monitor patients for signs and symptoms of neurologic toxicity during treatment.1 At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient; provide supportive therapy and consider further management per current practice guidelines.1 Withhold linvoseltamab-gcpt until ICANS resolves and modify the next dose or permanently discontinue linvoseltamab-gcpt based on severity.1 Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.1
Due to the potential for neurologic toxicity, including ICANS, patients receiving linvoseltamab-gcpt are at risk of confusion and depressed consciousness.1 Advise patients to refrain from driving, or operating heavy or potentially dangerous machinery, for 48 hours after completion of each of the step-up doses and in the event of new onset of any neurological symptoms, until symptoms resolve.1
Linvoseltamab-gcpt is available only through a restricted program under a REMS called the linvoseltamab-gcpt REMS because of the risks of CRS and neurologic toxicity, including ICANS.1
Notable requirements of the linvoseltamab-gcpt REMS include the following: 1
Further information about the linvoseltamab-gcpt REMS program is available at [Web] or by telephone at 1-855-212-6391.1
Linvoseltamab-gcpt can cause serious, life-threatening, or fatal infections. 1
In patients who received linvoseltamab-gcpt at the recommended dose in LINKER-MM1, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade 3 or 4 infections in 38% and fatal infections in 4%.1 The most common serious infection reported (≥10%) were pneumonia and sepsis.1 Two cases of progressive multifocal leukoencephalopathy (PML) occurred in patients receiving linvoseltamab-gcpt.1
Monitor patients for signs and symptoms of infection and immunoglobulin levels prior to and during treatment with linvoseltamab-gcpt and treat appropriately.1 Administer prophylactic antimicrobials, antibiotics, antifungals, antivirals, vaccines, and subcutaneous or IV immunoglobulin (IVIG) according to guidelines, including prophylaxis for PJP and herpes viruses.1
Withhold linvoseltamab-gcpt or consider permanent discontinuation of linvoseltamab-gcpt based on severity of the infection.1
Linvoseltamab-gcpt can cause neutropenia and febrile neutropenia. 1
In patients who received linvoseltamab-gcpt at the recommended dose in LINKER-MM1, decreased neutrophil count occurred in 62% of patients with Grade 3 or 4 decreased neutrophil count in 47%.1 Febrile neutropenia occurred in 8% of patients.1
Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local guidelines.1 Monitor patients with neutropenia for signs of infection.1 Withhold linvoseltamab-gcpt based on severity.1
Linvoseltamab-gcpt can cause hepatotoxicity. 1
In LINKER-MM1, elevated ALT occurred in 46% of patients, with Grade 3 or 4 ALT elevation occurring in 6%; elevated AST occurred in 61% of patients, with Grade 3 or 4 AST elevation occurring in 10% of patients who received the recommended dose.1 Grade 3 or 4 total bilirubin elevations occurred in 1.7% of patients.1 Liver enzyme elevation can occur with or without concurrent CRS.1
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.1 Withhold linvoseltamab-gcpt or consider permanent discontinuation of linvoseltamab-gcpt based on severity. 1
Based on its mechanism of action, linvoseltamab-gcpt may cause fetal harm when administered to a pregnant woman.1 Advise pregnant women of the potential risk to the fetus.1 Advise females of reproductive potential to use effective contraception during treatment with linvoseltamab-gcpt and for 3 months after the last dose.1
Based on the mechanism of action, linvoseltamab-gcpt may cause fetal harm when administered to a pregnant woman.1 There are no available data on the use of linvoseltamab-gcpt in pregnant women to evaluate for a drug associated risk.1 No animal reproductive or developmental toxicity studies have been conducted with linvoseltamab-gcpt.1
Linvoseltamab-gcpt causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance.1 In addition, based on the finding of B-cell depletion in non-pregnant animals, linvoseltamab-gcpt can cause B-cell lymphocytopenia in infants exposed to linvoseltamab-gcpt in-utero.1 Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy; therefore, linvoseltamab-gcpt has the potential to be transmitted from the mother to the developing fetus.1 Advise women of the potential risk to the fetus.1
Linvoseltamab-gcpt is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with linvoseltamab-gcpt should be considered.1
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.1
There are no data on the presence of linvoseltamab-gcpt in human milk, the effects on the breastfed child, or the effects on milk production.1 Maternal IgG is known to be present in human milk.1
Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with linvoseltamab-gcpt and for 3 months after the last dose.1
Females and Males of Reproductive Potential
Linvoseltamab-gcpt may cause fetal harm when administered to a pregnant woman.1
Verify the pregnancy status of females of reproductive potential prior to initiating treatment with linvoseltamab-gcpt.1
Advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of linvoseltamab-gcpt.1
The safety and effectiveness of linvoseltamab-gcpt have not been established in pediatric patients.1
Of the 117 patients with relapsed or refractory multiple myeloma who received linvoseltamab-gcpt, 42 (36%) of patients were 65 to 74 years of age and 31 (26%) were 75 years of age and older.1 No overall differences in safety or effectiveness were observed in patients 65 years of age and older, including patients 75 years of age and older, when compared with younger patients.1
The most common adverse reactions (≥20%) are musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea.1
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.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Please see product labeling for drug interaction information.
Linvoseltamab-gcpt is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.1
In vitro, linvoseltamab-gcpt activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells.1 Linvoseltamab-gcpt had anti-tumor activity in mouse models of multiple myeloma.1
Additional Information
AHFS first Release™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use | 5 mg/2.5 mL | Lynozyfic® | Regeneron Pharmaceuticals Inc. |
200 mg/10 mL | Lynozyfic® | Regeneron Pharmaceuticals Inc. |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions December 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Regeneron Pharmaceuticals, Inc.. LYNOZYFIC® (linvoseltamab-gcpt) INTRAVENOUS prescribing information. 2025 Jul. [Web]