What are the precautions for Linvoseltamab?

In the clinical study of Linvoseltamab (rivosetantumab) in the treatment of multiple myeloma (MM), warnings and precautions such as cytokine release syndrome, neurotoxicity (including immune effector cell-associated neurotoxicity syndrome), infection, neutropenia, hepatotoxicity, embryo-fetotoxicity, etc. emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Cytokine Release Syndrome (CRS): This can be serious or life-threatening. Clinical signs and symptoms of CRS include, but are not limited to, fever, chills, hypoxia, tachycardia, and hypotension. Administer pretreatment medication and initiate treatment based on escalating doses of LYNOZYFIC to reduce the incidence and severity of CRS. Monitor patients for signs and symptoms of CRS after infusion. If signs or symptoms of CRS occur, patients are advised to seek immediate medical attention. At the first sign of CRS, assess the patient immediately for hospitalization, manage according to current practice guidelines, and implement supportive care.

Infusion-related reactions (IRR) may be clinically indistinguishable from the manifestations of CRS. The incidence of IRR was 9% among patients treated with the recommended escalating dose regimen and conditioning medications. For IRRs, interrupt or slow the infusion rate or permanently discontinue based on the severity of the reaction.

2. Neurotoxicity, including immune effector cell-associated neurotoxic syndrome (ICANS): Neurotoxicity includes ICANS, decreased level of consciousness, encephalopathy, and toxic encephalopathy. The most common clinical signs and symptoms are confusion, low level of consciousness, and somnolence. Monitor patients for signs and symptoms of neurotoxicity during treatment. Evaluate patients promptly at the first sign of neurotoxicity, including ICANS; provide supportive care and consider further management according to current practice guidelines. If signs or symptoms of neurotoxicity occur at any time, patients are advised to seek immediate medical attention.

There is a risk of confusion and depression in patients receiving Linvoseltamab due to potential neurotoxicity, including ICANS. Advise patients to avoid driving or operating heavy or potentially hazardous machinery for 48 hours after completing each incremental dose and in the event of any new neurological symptoms until symptoms resolve.

3. Infection: Can cause serious, life-threatening or fatal infection. The most common serious infections (≥10%) were pneumonia and sepsis. Monitor patients for signs and symptoms of infection and immunoglobulin levels before and during treatment with linvoseltamab and treat appropriately. Take prophylactic antibacterials, antibiotics, antifungals, antivirals, vaccines, and subcutaneous or intravenous immune globulin (IVIG) according to guidelines, including prevention of PJP and herpes viruses.

4. Neutropenia: Linvoseltamab can cause neutropenia and febrile neutropenia. Monitor complete blood counts at baseline and periodically during treatment, and provide supportive care according to local guidelines. Monitor neutropenic patients for signs of infection.

5. Hepatotoxicity: In clinical studies, patients will experience elevated ALT, elevated AST, elevated total bilirubin, and elevated liver enzymes with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Depending on severity, discontinue use or consider permanent discontinuation.

6. Embryo-fetal toxicity: According to its mechanism of action, Linvoseltamab may cause harm to the fetus when used by pregnant women. Inform pregnant women of potential risks to the fetus. Advise females of childbearing potential to use effective contraception during treatment and for 3 months after the last dose.

Reference materials:https://en.wikipedia.org/wiki/Linvoseltamab