Regeneron Lynozyfic page 5 of 6 4C (near Multiple Myeleoma) LYNOZYFIC™ (linvoseltamab-gcpt) injection, for intravenous use Brief Summary of Prescribing Information 1 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 [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Cytokine Release Syndrome (CRS) LYNOZYFIC can cause cytokine release syndrome (CRS), which can be serious or life-threatening. In LINKER-MM1, CRS occurred in 46% (54/117) of patients who received LYNOZYFIC 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) [see Adverse Reactions (6.1)]. 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. 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 LYNOZYFIC, and 3.6% (4/110) developed CRS after the second full dose. Recurrent CRS occurred in 20% (23/117) of patients. 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. Clinical signs and symptoms of CRS included, but were not limited to pyrexia, chills, hypoxia, tachycardia, and hypotension. Administer pretreatment medications and initiate therapy according to LYNOZYFIC step-up dosing to reduce the incidence and severity of CRS [see Dosage and Administration (2.2) and Dosage and Administration (2.3)]. Monitor patients for signs and symptoms of CRS after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. Infusion Related Reactions Infusion-related reactions (IRR) may be clinically indistinguishable from manifestations of CRS. In the patients who were treated with the recommended step-up dosing regimen and pretreatment medications [see Dosage and Administration (2.2) and Dosage and Administration (2.3)], the rate of IRR was 9% [11/117 including Grade 2 IRR (4.3%) and Grade 3 IRR (1.7%)]. For IRR, interrupt or slow the rate of infusion or permanently discontinue LYNOZYFIC based on severity of reaction [see Dosage and Administration (2.5)]. LYNOZYFIC is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)]. 5.2 Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome LYNOZYFIC can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Adverse Reactions (6.1)]. In LINKER-MM1, neurologic toxicity occurred in 54% of patients, with Grade 3 or 4 neurologic toxicity occurring in 8% at the recommended dose [see Adverse Reactions (6.1)]. Neurologic toxicities included ICANS, depressed level of consciousness, encephalopathy, and toxic encephalopathy. ICANS occurred in 8% of patients who received LYNOZYFIC with the recommended dosing regimen, including Grade 3 events in 2.6%. Most patients experienced ICANS following step-up dose 1 (5%). 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 LYNOZYFIC. Recurrent ICANS occurred in one patient. 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. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. The most common clinical signs and symptoms of ICANS are confusion, depressed level of consciousness, and lethargy. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient; provide supportive therapy and consider further management per current practice guidelines. Withhold LYNOZYFIC until ICANS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time. Due to the potential for neurologic toxicity, including ICANS, patients receiving LYNOZYFIC are at risk of confusion and depressed consciousness. 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 [see Dosage and Administration (2.2)] and in the event of new onset of any neurological symptoms, until symptoms resolve. LYNOZYFIC is available only through a restricted program under a REMS [see Warnings and Precautions (5.3)]. 5.3 LYNOZYFIC REMS LYNOZYFIC is available only through a restricted program under a REMS called the LYNOZYFIC REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1, 5.2)]. Notable requirements of the LYNOZYFIC REMS include the following: • Prescribers must be certified with the program by enrolling and completing training. • Prescribers must counsel patients receiving LYNOZYFIC about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with LYNOZYFIC Patient Wallet Card. • Pharmacies and healthcare settings that dispense LYNOZYFIC must be certified with the LYNOZYFIC REMS program and must verify prescribers are certified through the LYNOZYFIC REMS program. • Wholesalers and distributors must only distribute LYNOZYFIC to certified pharmacies or healthcare settings. Further information about the LYNOZYFIC REMS program is available at LynozyficREMS.com or by telephone at 1-855-212-6391. 5.4 Infections LYNOZYFIC can cause serious, life-threatening, or fatal infections. In patients who received LYNOZYFIC 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% [see Adverse Reactions (6.1)]. The most common serious infection reported (≥10%) were pneumonia and sepsis. Two cases of progressive multifocal leukoencephalopathy (PML) occurred in patients receiving LYNOZYFIC. Monitor patients for signs and symptoms of infection and immunoglobulin levels prior to and during treatment with LYNOZYFIC and treat appropriately. Administer prophylactic antimicrobials, antibiotics, antifungals, antivirals, vaccines, and subcutaneous or intravenous immunoglobulin (IVIG) according to guidelines, including prophylaxis for PJP and herpesviruses [see Dosage and Administration (2.3)]. Withhold LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity of the infection [see Dosage and Administration (2.5)]. 5.5 Neutropenia LYNOZYFIC can cause neutropenia and febrile neutropenia. In patients who received LYNOZYFIC 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%. Febrile neutropenia occurred in 8% of patients [see Adverse Reactions (6.1)]. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local guidelines. Monitor patients with neutropenia for signs of infection. Withhold LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. 5.6 Hepatotoxicity LYNOZYFIC can cause hepatotoxicity. 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. Grade 3 or 4 total bilirubin elevations occurred in 1.7% of patients [see Adverse Reactions (6.1)]. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity [see Dosage and Administration (2.5)]. 5.7 Embryo-Fetal Toxicity Based on its mechanism of action, LYNOZYFIC may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with LYNOZYFIC and for 3 months after the last dose [see Use in Specific Populations (8.1, 8.3)]. 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Cytokine Release Syndrome [see Warnings and Precautions (5.1)] • Neurologic Toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome [see Warnings and Precautions (5.2)] • Infections [see Warnings and Precautions (5.4] • Neutropenia [see Warnings and Precautions (5.5)] • Hepatotoxicity [see Warnings and Precautions (5.6)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed or Refractory Multiple Myeloma The safety of LYNOZYFIC was evaluated in LINKER-MM1 [see Clinical Studies (14)]. Patients (n=117) received a single step-up dose of 5 mg on Day 1 and 25 mg on Day 8, and the first treatment dose of 200 mg on Day 15. Patients then received 200 mg intravenously once weekly from Week 4 to Week 13, followed by 200 mg every 2 weeks from Week 14. In the Phase 2 portion of the study, patients who achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg were able to receive every 4-week dosing. The median duration of treatment was 47 weeks (range 1, 151); 55% of patients were exposed for 9 months or longer and 36% were exposed for 1 year or longer. The median age of patients who received LYNOZYFIC was 70 years (range: 37 to 91 years); 55% were male; 71% were White, 17% were Black or African American, and 9% were Asian. WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, INCLUDING IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME • Cytokine release syndrome (CRS), including serious or life-threatening 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 [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.1)]. • 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 [see Dosage and Administration (2.2, 2.4, 2.5) and Warnings and Precautions (5.2)]. • Because of the risk of CRS and neurologic toxicity, including ICANS, LYNOZYFIC is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the LYNOZYFIC REMS [see Warnings and Precautions (5.3)].
View this content as a flipbook by clicking here.