ELREXFIO

/ Pfizer

The recommended doses are step-up doses of 12 mg on day 1 and 32 mg on day 4, followed by a full treatment dose of 76 mg weekly from week 2 to week 24. For patients who have received at least 24 weeks of treatment and have achieved a response, the dosing interval should transition to every two-week schedule.
See prescribing information for full details.

Treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

Hypersensitivity to the active substance or to any of the excipients.

Cytokine release syndrome (CRS)
CRS, including life-threatening or fatal reactions, may occur in patients receiving this medical product.
Therapy should be initiated according to the step-up dosing schedule to reduce risk of CRS and patients should be monitored following administration of Elranatamab  accordingly. Pre-treatment medicinal products should be administered prior to the first three doses to reduce risk of CRS.
Neurologic toxicities, including ICANS
Serious or life-threatening neurologic toxicities, including ICANS, may occur following treatment with Elranatamab. Patients should be monitored for signs and symptoms (e.g., decrease level of consciousness, seizures and/or motor weakness) of neurologic toxicities during treatment.
Due to the potential for ICANS, patients should be advised not to drive or operate heavy or potential dangerous machinery during the step-up dosing schedule and for 48 hours after completing each of the 2 step-up doses and in the event of new onset of any neurological symptoms.
Infections
Severe, life-threatening, or fatal infections have been reported in patients receiving Elranatamab. New or reactivated viral infections occurred during therapy with Elranatamab, including cytomegalovirus (CMV) infection/reactivation. Progressive multifocal leukoencephalopathy (PML) has also occurred during therapy with Elranatamab.
Treatment should not be initiated in patients with active infections. Patients should be monitored for signs and symptoms of infection prior to and during treatment with Elranatamab and treated appropriately. Elranatamab should be withheld based on the severity of the infection.
Prophylactic antimicrobials (e.g., prevention of pneumocystis jirovecii pneumonia) and anti-virals (e.g., prevention of herpes zoster reactivation) should be administered according to local institutional guidelines.
Neutropenia
Neutropenia and febrile neutropenia have been reported in patients receiving Elranatamab. Complete blood cell counts should be monitored at baseline and periodically during treatment.
Hypogammaglobulinaemia
Hypogammaglobulinemia has been reported in patients receiving Elranatamab. Immunoglobulin levels should be monitored during treatment. Treatment with subcutaneous or intravenous immunoglobulin (IVIG) should be considered if IgG levels fall below 400 mg/dL and patients should be treated according to local institutional guidelines, including infection precautions and antimicrobial prophylaxis.
Concomitant use of live viral vaccines
The safety of immunisation with live viral vaccines during or following treatment with Elranatamab has not been studied. Vaccination with live virus vaccines is not recommended within the 4 weeks prior to the first dose, during treatment, and at least 4 weeks after treatment.
See prescribing information for full details.

The most frequent adverse reactions are CRS (57.9%), anaemia (54.1%), neutropenia (44.8%), fatigue (44.3%), upper respiratory tract infection (38.8%), injection site reaction (38.3%), diarrhoea (37.7%), pneumonia (37.2%), thrombocytopenia (36.1%), lymphopenia (30.1%), decreased appetite (26.8%), pyrexia (27.3%), rash (26.2%), arthralgia (25.1%), hypokalaemia (23.0%), nausea (21.3%), and dry skin (21.3%). Serious adverse reactions are pneumonia (30.6%), sepsis (15.3%), CRS (12.6%), anaemia (5.5%), upper respiratory tract infection (4.9%), urinary tract infection (3.3%), febrile neutropenia (2.7%), dyspnoea (2.2%), and pyrexia (2.2%).

No interaction studies have been performed.
The initial release of cytokines associated with the start of Elranatamab may suppress cytochrome P450 (CYP) enzymes. The highest risk of interaction is expected to occur during and up to 14 days after the step-up dosing as well as during and up to 14 days after CRS. During this time period, toxicity or medicinal product concentrations should be monitored in patients who are receiving concomitant sensitive CYP substrates with a narrow therapeutic index (e.g., cyclosporine, phenytoin, sirolimus, and warfarin). The dose of the concomitant medicinal product should be adjusted as needed.

Women of child-bearing potential/Contraception
The pregnancy status of women of child-bearing potential should be verified prior to initiating treatment with this medical product.
Women of child-bearing potential should use effective contraception during treatment with Elranatamaband for 6 months after the last dose.
Pregnancy: There are no human or animal data to assess the risk of elranatamab use during pregnancy. Human immunoglobulin (IgG) is known to cross the placenta after the first trimester of pregnancy. Based on the mechanism of action, elranatamab may cause foetal harm when administered to a pregnant woman and therefore Elranatamab is not recommended for use during pregnancy.
Elranatamab is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with Elranatamab should be considered.
Lactation: It is not known whether elranatamab is excreted in human or animal milk, affects breastfed infants or affects milk production. Human IgGs are known to be excreted in breast milk. A risk to the breastfed child cannot be excluded and therefore breast-feeding is not recommended during treatment with Elranatamab and for 6 months after the last dose.

There has been no experience of overdose in clinical studies. The maximum tolerated dose of elranatamab has not been determined. In clinical studies, doses up to 76 mg once weekly have been administered.
Treatment
In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions and appropriate supportive treatment should be instituted immediately.