Regeneron
Lynozyfic
page 3 of 6
4C
(near Multiple 
Myeleoma)
IMPORTANT SAFETY INFORMATION (cont’d)
Warnings and Precautions (cont’d)
Cytokine Release Syndrome (CRS): (cont’d)
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, 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.
Neurologic Toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome: 
LYNOZYFIC can cause serious or life-threatening neurologic toxicity, including ICANS. In  
LINKER-MM1, neurologic toxicity occurred in 54% of patients, with Grade 3 or 4 neurologic toxicity 
occurring in 8%, at the recommended dose. 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. Counsel patients to seek immediate medical attention 
should signs or symptoms of neurologic toxicity, including ICANS 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 and in 
the event of new onset of any neurological symptoms, until symptoms resolve.
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. 
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%. 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. Withhold LYNOZYFIC or 
consider permanent discontinuation of LYNOZYFIC based on severity of the infection.

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