Linvoseltamab-gcpt, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, is an antineoplastic agent.1
Relapsed or Refractory Multiple Myeloma
Linvoseltamab-gcpt is used for the treatment of relapsed or refractory multiple myeloma in adult patients who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1 Linvoseltamab-gcpt has been designated an orphan drug by FDA for the treatment of multiple myeloma.2
Linvoseltamab-gcpt was 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
The current indication for linvoseltamab-gcpt is based principally on the results of an open-label, multi-center, multi-cohort, phase 2 study (LINKER-MM1; NCT03761108) in adult patients with relapsed or refractory multiple myeloma who had previously received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.1, 3 Patients were included if they had an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 and adequate baseline hematologic (defined as an absolute neutrophil count [ANC] >1000 cells/mm3, platelet count >50,000 cells/mm3, and hemoglobin >8 g/dL), renal (creatinine clearance >30 mL/minute), and hepatic (AST and ALT concentrations ≤2.5 times the upper limit of normal [ULN], total bilirubin concentration ≤1.5 times the ULN, and alkaline phosphatase concentration ≤2.5 times the ULN) function.1 Patients were excluded if they had known multiple myeloma brain lesions or meningeal involvement, a history of a neurodegenerative condition, a history of seizure within 12 months prior to enrollment, an active infection, a history of allogeneic or autologous stem cell transplantation within 12 weeks, prior bispecific B-cell maturation antigen (BCMA)-directed antibody therapy, prior bispecific T-cell engaging therapy, or prior BCMA chimeric antigen receptor T-cell (CAR-T) therapy.1, 3 Patients received a step-up linvoseltamab-gcpt IV infusion dose of 5 mg on day 1, 25 mg on day 8, and the first treatment dose of 200 mg on day 15.1 After step-up doses, patients received linvoseltamab-gcpt 200 mg weekly for weeks 4-13, followed by 200 mg every other week thereafter.1 After at least 24 weeks, patients who achieved a very good partial response or greater received linvoseltamab-gcpt 200 mg every 4 weeks until disease progression or unacceptable toxicity occurred.1, 3 Efficacy was based on an objective response rate as determined by a blinded independent review committee, as measured using the International Myeloma Working Group criteria.1, 3
A total of 80 patients were evaluated as the efficacy population.1 The median age of included patients from the efficacy population was 71 years (range: 37-83 years).1 The majority of patients were male (64%) and White (69%); 14% were Black or African American and 13% were Asian.1 The International Staging System (ISS) at entry to the study was Stage I in 39%, Stage II in 36%, and Stage III in 19% of patients.1 High-risk cytogenetics were present in 40% of patients and 18% percent of patients had extramedullary disease at baseline.1 The median number of prior lines of therapy was 5 (range: 4-13); 13% of patients were previously treated with a BCMA antibody-drug conjugate and 65% had received prior stem cell transplantation.1 Of the patients with refractory disease, 83% were refractory to the last line of therapy and 79% of patients were triple-class refractory (refractory to a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).1 The overall response rate was 70%; 45% of patients had a complete response or better, 19% had a very good partial response, and 6% had a partial response.1 The median time to first response was 0.95 months (range: 0.5-6 months).1 After a median follow up of 11.3 months among treatment responders, the estimated duration of response rate was 89% at 9 months and 72% at 12 months.1
The American Society of Clinical Oncology (ASCO) and Ontario Health (Cancer Care Ontario) published evidence-based recommendations for the treatment of multiple myeloma, including patients with relapsed or refractory disease.4, 5 For the treatment of relapsed or refractory disease, the guideline recommends triplet therapy or T-cell redirecting therapies for eligible patients.4, 5 Patients should be offered treatment regimens that include different agents from those in prior therapies whenever possible.4, 5 The bispecific antibodies, including linvoseltamab-gcpt, should be offered to eligible patients (including older and frail patients) where other options are not possible or exhausted.4, 5
Drug (Example or Equivalent) | Recommended Dose | Route of Administration | Dosing Window Prior to Infusion |
|---|---|---|---|
Acetaminophen | 650-1000 mg | Orally | Administer 30-60 minutes prior to infusion |
Diphenhydramine | 25 mg | IV or orally | Administer 30-60 minutes prior to infusion |
Dexamethasone | 40 mg prior to step-up dose 1, 2, and first full treatment dose If a treatment dose is tolerated without CRS and/or IRR after 40 mg, decrease to 10 mg prior to subsequent treatment dose | IV | Administer 1-3 hours prior to infusion |
Dispensing and Administration Precautions
Linvoseltamab-gcpt is administered by IV infusion through a dedicated IV line with a 0.2-5 µm polyethersulfone filter.1 Linvoseltamab-gcpt must be further diluted prior to IV administration.1
Linvoseltamab-gcpt should not be mixed with or administered with other drugs through the same IV line.1
Store unopened linvoseltamab-gcpt vials refrigerated at 2-8°C in the original carton, protected from light.1 Do not freeze or shake.1
Prior to administration, linvoseltamab-gcpt must be diluted using proper aseptic technique.1 Inspect the product visually for particulate matter or discoloration; linvoseltamab-gcpt should be a clear to slightly opalescent, colorless to pale yellow solution.1 The required dose of linvoseltamab-gcpt should be withdrawn from the vial and transferred into an IV infusion bag made of either polyvinyl chloride or polyolefin containing the recommended volume of 0.9% sodium chloride for injection according to Table 2.1 The diluted solution should be mixed by gentle inversion and should not be shaken.1
Dose | Vial Strength | Volume of Drug | Size of Infusion Bag Containing 0.9% Sodium Chloride |
|---|---|---|---|
2.5 mg | 5 mg/2.5 mL | 1.25 mL | 50 mL |
5 mg | 5 mg/2.5 mL | 2.5 mL | 50 mL or 100 mL |
25 mg | 5 mg/2.5 mL | 12.5 mL | 50 mL or 100 mL |
200 mg | 200 mg/10 mL | 10 mL | 50 mL or 100 mL |
Diluted linvoseltamab-gcpt should be used immediately.1 If not used immediately, the diluted solution should be stored at room temperature up to 25°C for no more than 8 hours from preparation to the start of the infusion or refrigerated at 2-8°C for no more than 48 hours from preparation to the start of the infusion.1 Diluted preparations should not be frozen or shaken.1
After dilution, the rate of infusion of linvoseltamab-gcpt is based on the dosing schedule (Table 3).1 Following completion of the linvoseltamab-gcpt infusion, the IV line should be flushed with an adequate volume of 0.9% sodium chloride for injection to ensure that the entire contents of the infusion bag are administered.1 The total infusion time should include flushing of the IV infusion line.1
Dosing Schedule | Infusion Day and Week | Duration of Infusion |
|---|---|---|
Step-up dosing schedule | Days 1, 8, and 15 | 4 hours |
Weekly dosing schedule | 1 week after day 15 treatment dose and once weekly from week 4-13 for 10 doses | 1 hour for the second treatment dose, then 30 minutes for subsequent dosesa |
Biweekly dosing schedule | Week 14 and every 2 weeks thereafter | 30 minutes |
Every 4 weeks dosing schedule | Week 24 or after and every 4 weeks thereafter | 30 minutes |
aFor patients who experienced CRS with the previous dose of linvoseltamab-gcpt, the duration of the infusion should be maintained at the duration of the previous infusion; reduce the duration of the infusion sequentially in subsequent doses in patients who do not experience CRS (e.g., 4 hours, then 1 hour, then 30 minutes).1
Relapsed or Refractory Multiple Myeloma
For the treatment of relapsed or refractory multiple myeloma in adult patients, linvoseltamab-gcpt should initially be administered according to a step-up dosing schedule (see Table 4).1
After completing the step-up dosing schedule, the recommended dosage of linvoseltamab-gcpt is 200 mg IV according to the dosing schedule in Table 4.1 Starting 1 week after completing the step-up dosing schedule (1 week after day 15), a weekly dosing schedule should be continued from week 4 to week 13, for a total of 10 treatment doses (see Table 4).1 At week 14, an every 2 weeks dosing schedule is continued.1 In patients who have achieved and maintained a very good positive response (VGPR) or better at or after week 24 and have received at least 17 doses of 200 mg, the recommended dosing schedule can be modified to every 4 weeks.1 Linvoseltamab-gcpt should be continued until disease progression or unacceptable toxicity.1
Weekly doses of linvoseltamab-gcpt should be administered at least 5 days apart.1 Biweekly doses of linvoseltamab-gcpt should be administered at least 10 days apart, and every 4-week doses should be administered at least 24 days apart.1
Dosing Schedule | Day | Dose |
|---|---|---|
Step-up dosing schedule | 1 | 5 mg |
Step-up dosing schedule | 8 | 25 mg |
Step-up dosing schedule | 15 | 200 mg |
Weekly dosing schedule | 1 week after day 15 treatment dose and once weekly from weeks 4-13 for 10 treatment doses | 200 mg |
Biweekly dosing schedule | Week 14 and every 2 weeks thereafter | 200 mg |
Every 4 weeks dosing schedule (in patients who have achieved and maintained VGPR or better) | Week 24 and every 4 weeks thereafter | 200 mg |
Dosage Interruption for Toxicity
Treatment delays may be required to manage toxicities of linvoseltamab-gcpt.1 When restarting linvoseltamab-gcpt after a treatment delay, recommendations for the next dose are guided by the time since the last dose was administered (see Table 5).1
When resuming linvoseltamab-gcpt after a treatment delay, premedications should be administered prior to step-up dose 1, step-up dose 2, the first and second treatment doses, and, if indicated, subsequent treatment doses.1
Last Dose Administered | Time Since Last Dose Administereda | Recommendation for Next Dose |
|---|---|---|
5 mg | ≤14 days | Administer 25 mg |
5 mg | >14 days | Restart step-up dosing from 5 mg |
25 mg | ≤14 days | Administer 200 mg |
25 mg | >14 days and ≤28 days | Restart step-up dosing from 25 mg |
25 mg | >28 days | Restart step-up dosing from 5 mg |
200 mg | ≤49 days | Administer 200 mg |
200 mg | >49 days | Restart step-up dosing from 5 mg |
aConsider risks and benefits of restarting linvoseltamab-gcpt in patients who require a treatment delay of >30 days.1
Dosage Modification for Toxicity
Treatment recommendations and dosage modifications (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) may be needed to manage adverse effects of linvoseltamab-gcpt.1
Cytokine Release Syndrome (CRS)
In patients with suspected CRS, evaluate and treat other causes of fever, hypoxia, and hypotension and withhold linvoseltamab-gcpt until CRS resolves.1 Recommendations for the management of and therapy modifications for CRS are based on severity as described in Table 6.1
Gradea | Presenting Symptoms | Treatment Recommendations and Dosage Modifications |
|---|---|---|
1 | Temperature ≥38°Cb | Withhold linvoseltamab-gcpt until CRS resolves Provide supportive care (may include intensive care) When CRS resolves, resume drug according to recommendations in Table 5; administer premedications prior to next dose |
2 | Temperature ≥38°Cb with:
| Withhold linvoseltamab-gcpt until CRS resolves Provide supportive care (may include intensive care) When CRS resolves, resume drug according to recommendations in Table 5, administer premedications prior to the next dose, and consider decreasing the infusion rate up to 50% (no more than 6 hours total); increase infusion rate on subsequent infusions, if tolerated Monitor patients within proximity of healthcare facility for 24 hours following next dose, and consider hospitalization |
3 | Temperature ≥38°Cb with:
| Withhold linvoseltamab-gcpt until CRS resolves Provide support care (may include intensive care) When CRS resolves, resume treatment at reduced dosaged, administer premedications prior to the next dose, and decrease the infusion rate up to 50% (no more than 6 hours total); hospitalize for 24 hours after administration of this dose After resuming treatment, if administered dose is tolerated, continue with next dose of the recommended dosing regimen according to Table 4; if the full dose is tolerated, the infusion rate can be increased to the rate prior to the adverse effect Permanently discontinue drug if grade 3 CRS recurs with subsequent infusions |
4 | Temperature ≥38°Cb with:
| Manage CRS according to grade 3 recommendations Permanently discontinue linvoseltamab-gcpt |
Other | AST/ALT concentrations exceeding 5 times the upper limit of normal (ULN) associated with grade 3 CRS or less | Withhold linvoseltamab-gcpt until CRS resolves and AST/ALT concentrations are <3 times the ULN if baseline concentrations were normal or 1.5-3 times baseline concentrations if the baseline concentrations were abnormal Provide supportive care (may include intensive care) and monitor No change in dosage is needed in patients without CRS symptoms with aminotransferase concentrations that are trending towards baseline within 7 days If aminotransferase concentrations do not trend towards baseline within 7 days, decrease the dosaged Adjust infusion rate by CRS grade |
aBased on the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading criteria for CRS1
bAttributed to CRS; fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as corticosteroids, antipyretics, or anti-cytokine therapy.1
cLow-flow oxygen defined as oxygen delivered at less than 6 L/minute; high-flow oxygen defined as oxygen delivered at ≥6 L/minute.1
dIf the last dose administered was 5 mg, administer 2.5 mg.1 If the last dose administered was 25 mg, restart step-up dosing from 5 mg.1 If the last dose administered was 200 mg, refer to Table 4 for recommendations regarding restarting therapy based on time since the last dose.1
At the first sign of suspected neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), withhold linvoseltamab-gcpt and consider consultation with neurologist and other specialists for further evaluation and management.1 Recommendations for the management of and therapy modifications for neurologic toxicity, including ICANS, are based on severity as described in Tables 7 and 8.1
Gradea | Presenting Symptomsb | Treatment Recommendations and Dosage Modifications |
|---|---|---|
1 | ICE score 7-9c, OR Depressed level of consciousness (not attributable to other cause); awakens spontaneously | Withhold linvoseltamab-gcpt until neurologic symptoms resolve or return to baseline, then follow recommendations in Table 5 for restarting therapy Provide supportive therapy and manage per current practice guidelines Consider non-sedating anticonvulsants for seizure prophylaxis |
2 | ICE score 3-6c, OR Depressed level of consciousness (not attributable to other cause); awakens to voice | Withhold linvoseltamab-gcpt until neurologic symptoms resolve or return to baseline, then follow recommendations in Table 5 for restarting therapy Provide supportive therapy (may include intensive care) and manage per current practice guidelines Administer dexamethasone 10 mg (or equivalent) IV every 6 hours; continue dexamethasone until resolution to grade 1 or less, then taper Consider non-sedating anticonvulsants for seizure prophylaxis Monitor patients within proximity of healthcare facility for 24 hours following next dose, and consider hospitalization |
3 | ICE score 0-3c, OR Depressed level of consciousness (not attributable to other cause); awakens only to tactile stimulus, OR Seizures, either : any clinical seizure, focal, or generalized, that resolves rapidly, or non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, OR Raised intracranial pressure: focal/local edema on neuroimaging | Withhold linvoseltamab-gcpt until neurologic symptoms resolve or return to baseline Provide supportive therapy (may include intensive care) and manage per current practice guidelines; consider neurology evaluation Administer dexamethasone 10 mg (or equivalent) IV every 6 hours; continue dexamethasone until resolution to grade 1 or less, then taper Consider non-sedating anticonvulsants for seizure prophylaxis Resume treatment with linvoseltamab-gcpt at a reduced dosagedand hospitalize for 24 hours after administration of the dose; after resuming treatment, if the administered dose is tolerated, continue with the next dose of the recommended dosing regimen per Table 4 Permanently discontinue linvoseltamab-gcpt for recurrent grade 3 ICANS |
4 | ICE score 0c, OR Depressed level of consciousness (not attributable to other cause), either : patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, OR Motor findings of deep focal motor weakness such as hemiparesis or paraparesis, OR Raised intracranial pressure/cerebral edema, with signs/symptoms such as diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing's triad | Provide supportive therapy (may include intensive care) and manage per current practice guidelines; consider neurology evaluation Administer dexamethasone 10 mg (or equivalent) IV every 6 hours; continue dexamethasone until resolution to grade 1 or less, then taper Consider non-sedating anticonvulsants for seizure prophylaxis Permanently discontinue linvoseltamab-gcpt |
aBased on the ASTCT 2019 grading for ICANS.1
bManagement is determined by the most severe event, not attributable to any other cause.1
cIf patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: orientation (orientated to year, month, city, hospital = 4 points); naming (name 3 objects, e.g., point to clock, pen, button = 3 points); following commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue"); writing (ability to write a standard sentence = 1 point); and attention (count backwards from 100 by ten = 1 point).1 If patient is unarousable and unable to perform ICE assessment (Grade 4 ICANS) = 0 points.1
dIf the last dose administered was 5 mg, administer 2.5 mg.1 If the last dose administered was 25 mg, restart step-up dosing from 5 mg.1 If the last dose administered was 200 mg, refer to Table 4 for recommendations regarding restarting therapy based on time since the last dose.1
Grade | Treatment Recommendations and Dosage Modifications |
|---|---|
2 | Withhold linvoseltamab-gcpt until symptoms resolve to grade 1 or baseline Resume drug according to recommendations in Table 5 |
3 (First occurrence) | Withhold linvoseltamab-gcpt until symptoms resolve to grade 1 or baseline Resume drug according to recommendations in Table 5 |
3 (Recurrent) or 4 | Permanently discontinue linvoseltamab-gcpt |
Recommendations for the management of and therapy modifications for other toxicities are based on severity as described in Table 9.1
Adverse Effect | Grade/Severitya< | Treatment Recommendations and Dosage Modifications |
|---|---|---|
Infusion-related reactions (IRR) | 2 | Stop infusion and treat symptoms May resume treatment with remaining infusion when symptoms are grade 1 or baseline (total infusion time must not exceed 6 hours total) Consider decreasing infusion rate by up to 50% when resuming treatment; if tolerated, infusion rate can be increased with subsequent doses |
3 | Stop infusion and treat symptoms May resume treatment with remaining infusion when symptoms are grade 1 or baseline After resolution, decrease the infusion rate by up to 50% (total infusion time must not exceed 6 hours total) and resume at reduced dosageb; if the administered dose is tolerated, continue with the next dose of the recommended dosing regimen at the decreased infusion rate and increase infusion rate, if tolerated Permanently discontinue linvoseltamab-gcpt if grade 3 IRR recurs with subsequent infusions | |
4 | Permanently discontinue linvoseltamab-gcpt and treat symptoms | |
Infections | Grade 2-3 | Withhold linvoseltamab-gcpt in patients with active infection until the infection improves to grade 1 or less Resume drug according to recommendations in Table 5 |
4 | Consider permanent discontinuation of linvoseltamab-gcpt If treatment is not permanently discontinued, withhold subsequent treatment doses until grade 1 or baseline; resume drug according to recommendations in Table 5 | |
Hematologic adverse effects | Platelet count <50,000 cells/mm3with bleeding OR <25,000 cells/mm3 | Withhold linvoseltamab-gcpt until platelet count is ≥25,000 cells/mm3 and there is no evidence of bleeding Resume drug according to recommendations in Table 5 |
Absolute neutrophil count (ANC) <1000 cells/mm3 with grade 2 or higher infection OR ANC <500 cells/mm3 | Withhold linvoseltamab-gcpt until ANC ≥500 cells/mm3 Resume drug according to recommendations in Table 5 | |
Febrile neutropenia | Withhold linvoseltamab-gcpt until neutrophil count is >1000 cells/mm3 and fever resolves Resume drug according to recommendations in Table 5 | |
Hemoglobin <8 g/dL | Withhold linvoseltamab-gcpt until hemoglobin ≥8 g/dL Resume drug according to recommendations in Table 5 | |
Other non-hematologic adverse effects | 3 | Withhold linvoseltamab-gcpt until grade 1 or baseline Resume drug according to recommendations in Table 5 |
4 | Consider permanent discontinuation of linvoseltamab-gcpt If linvoseltamab-gcpt is not permanently discontinued, withhold subsequent treatment until grade 1 or baseline; resume drug according to recommendations in Table 5 |
aBased on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.1
bIf the last dose administered was 5 mg, administer 2.5 mg.1 If the last dose administered was 25 mg, restart step-up dosing from 5 mg.1 If the last dose administered was 200 mg, refer to Table 4 for recommendations regarding restarting therapy based on time since the last dose.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Linvoseltamab-gcpt can cause cytokine release syndrome (CRS), which can be serious or life-threatening.1 A boxed warning regarding this risk has been included in the prescribing information for linvoseltamab-gcpt.1
In the LINKER-MM1 study, CRS occurred in 46% of patients who received linvoseltamab-gcpt at the recommended dose, with Grade 1 CRS occurring in 35% of patients, Grade 2 in 10% , and Grade 3 in 0.9%.1 Thirty-eight percent of patients had CRS following step-up dose 1, including 1 patient who experienced Grade 3 CRS; 8% had an initial CRS event following a subsequent dose.1 Seventeen percent of patients developed CRS after step-up dose 2 of linvoseltamab-gcpt, 10% developed CRS after the first full 200-mg dose, and 3.6% developed CRS after the second full dose.1 Recurrent CRS occurred in 20% of patients.1 The median time to onset of CRS from the end of infusion was 11 hours (range: -1 to 184) after the most recent dose with a median duration of 15 hours (range: 1 to 76).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 the linvoseltamab-gcpt step-up dosing schedule 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%, including 4.3% Grade 2 IRR and 1.7% Grade 3 IRR.1 For IRR, interrupt or slow the rate of infusion or permanently discontinue linvoseltamab-gcpt based on severity of reaction.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 A boxed warning regarding this risk has been included in the prescribing information for linvoseltamab-gcpt.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 1 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 day (range: 1 to 4) after the most recent dose with a median duration of 2 days (range: 1 to 11).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 with linvoseltamab-gcpt.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 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 infections 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 Pneumocystis jirovecii pneumonia (PJP) and herpes viruses.1
Withhold 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 CBC at baseline and periodically during treatment with linvoseltamab-gcpt and provide supportive care per local guidelines.1 Monitor patients with neutropenia for signs of infection.1
Withhold linvoseltamab-gcpt based on severity of neutropenia.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%.1 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 concentration elevations occurred in 1.7% of patients.1 Liver enzyme elevation can occur with or without concurrent CRS.1
Monitor liver enzyme and bilirubin concentrations at baseline and during treatment as clinically indicated.1
Withhold 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
During treatment in LINKER-MM1 (evaluated through 30 months), 1% of patients treated with linvoseltamab-gcpt developed anti-linvoseltamab-gcpt antibodies.1 Because of the low occurrence, the effect of anti-drug antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of linvoseltamab-gcpt is unknown.1
There are no available data on the use of linvoseltamab-gcpt in pregnant women to evaluate for a drug-associated risk.1 Based on the mechanism of action, linvoseltamab-gcpt may cause fetal harm when administered to a pregnant woman.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; assessment of immunoglobulin levels in newborns of mothers treated with linvoseltamab-gcpt should be considered.1
There are no data on the presence of linvoseltamab-gcpt in human milk, the effects on the breast-fed 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 the breast-fed child, advise women not to breast-feed 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 patients (36%) were 65-74 years of age and 31 patients (26%) were ≥75 years of age.1 No overall differences in safety or effectiveness were observed in patients ≥65 years of age, including patients ≥75 years of age, when compared with younger patients.1
No clinically important differences in the pharmacokinetics of linvoseltamab-gcpt were observed in patients with mild hepatic impairment (total bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration exceeding the ULN, or total bilirubin concentration exceeding 1-1.5 times the ULN with any AST concentration).1 The effect of moderate to severe hepatic impairment (total bilirubin concentration exceeding 1.5 times the ULN with any AST concentration) on the pharmacokinetics of linvoseltamab-gcpt are unknown.1
No clinically important differences in the pharmacokinetics of linvoseltamab-gcpt were observed in patients with mild to moderate renal impairment (creatinine clearance 30-89 mL/minute by Cockcroft-Gault equation).1 The effect of severe renal impairment (creatinine clearance 15-29 mL/minute) and end-stage renal disease (creatinine clearance <15 mL/minute) on the pharmacokinetics of linvoseltamab-gcpt are unknown.1
The most common adverse effects of linvoseltamab-gcpt (incidence ≥20%) are musculoskeletal pain, CRS, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea.1
The most common Grade 3 or Grade 4 laboratory abnormalities of linvoseltamab-gcpt (incidence ≥30%) are decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Linvoseltamab-gcpt causes the release of cytokines that may suppress cytochrome P-450 (CYP) enzyme activity.1 Concomitant use with linvoseltamab-gcpt increases CYP substrate exposure, which may increase the risk of adverse effects of these substrates.1 Increased CYP substrate exposure is more likely to occur from initiation of the linvoseltamab-gcpt step-up dosing schedule up to 14 days after the first 200-mg dose, and during and after cytokine release syndrome.1
Monitor for toxicity, unless otherwise recommended in the Prescribing Information, of certain CYP substrates where minimal changes in the concentration may lead to serious adverse effects when used concomitantly with linvoseltamab-gcpt.1
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 activates T-cells, causes the release of various proinflammatory cytokines, and results in the lysis of multiple myeloma cells.1 Transient elevations of circulating cytokines interleukin (IL)-2, IL-6, tumor necrosis factor-alpha, and interferon-gamma is primarily observed during the step-up dosing regimen and the first full 200-mg dose of linvoseltamab-gcpt.1 The highest elevation of cytokines is generally observed 4 hours after each infusion of linvoseltamab-gcpt and generally returns to baseline prior to the next dose.1 Limited cytokine release was observed following subsequent doses.1 Linvoseltamab-gcpt had anti-tumor activity in mouse models of multiple myeloma.1
Linvoseltamab-gcpt trough concentrations increase more than proportionally over a dose range of 96-800 mg.1 Maximum plasma concentrations are reached after the first dose of the every 2-weeks dosing regimen (i.e., dose 12 of 200 mg).1 Linvoseltamab-gcpt exposure-response relationships have not been fully characterized.1 The clearance of linvoseltamab-gcpt decreases over time because its elimination is mediated by two parallel processes, which include a linear, non-saturable catabolic process and a non-linear, saturable target-mediated pathway.1 The maximum plasma concentration of linvoseltamab-gcpt is expected to decrease by 97% after a median time of 77.7 days (range: 18-154) following discontinuation.1 The metabolism of linvoseltamab-gcpt is expected to occur via metabolism to small peptides by catabolic pathways.1 Age (range: 37-91 years), weight (range: 44-172 kg), sex, race (White, Black, or Asian), ethnicity, mild to moderate renal impairment (creatinine clearance 30-89 mL/minute by Cockcroft-Gault equation), or mild hepatic impairment (total bilirubin concentration not exceeding the upper limit of normal [ULN] with AST concentration exceeding the ULN, or total bilirubin concentration exceeding 1-1.5 times the ULN with any AST concentration), do not impact the pharmacokinetics of linvoseltamab-gcpt.1 The impact of several renal impairment (creatinine clearance 15-29 mL/minute), end-stage renal disease (creatinine clearance <15 mL/minute), and moderate to severe hepatic impairment (total bilirubin concentration exceeding 1.5 times the ULN with any AST concentration) on the pharmacokinetics of linvoseltamab-gcpt are not known.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Linvoseltamab-gcpt is available only from designated specialty distributors. Contact manufacturer or consult the [Web] website for specific availability information.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use | 5 mg/2.5 mL (2 mg/mL) | Lynozyfic® | Regeneron Pharmaceuticals |
200 mg/10 mL (20 mg/mL) | Lynozyfic® | Regeneron Pharmaceuticals |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions October 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Regeneron Pharmaceuticals, Inc. Lynozyfic® (linvoseltamab-gcpt) injection for intravenous infusion prescribing information. Tarrytown, NY; 2025 Jul.
2. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2026 Jul 26. [Web]
3. Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol . 2024;42(22):2702-2712.
4. Hicks LK, Messersmith HJ, Al Hadidi S, et al. Treatment of multiple myeloma: ASCO-Ontario Health (Cancer Care Ontario) living guideline. J Clin Oncol . 2026;44(10):914-941.
5. American Society of Clinical Oncology. Treatment of multiple myeloma: ASCO living guideline, v2026.1.2. Updated 2026 June 26. Accessed 2026 Aug 2. [Web]
6. Institute for Safe Medication Practices (ISMP). ISMP list of high-alert medications in acute care settings (2024). Accessed 2026 July 28. [Web]
7. Regeneron Pharmaceuticals, Inc. Lynozyfic® risk evaluation and mitigation strategy (REMS). Accessed 2026 Aug 2. [Web]
8. US Food and Drug Administration. Approved risk evaluation and mitigation strategies (REMS). From FDA website. Accessed 2026 Aug 2. [Web]