Pepaxti

Treatment with Pepaxti must be initiated and supervised by physicians experienced in the treatment of multiple myeloma. Posology The recommended starting dose of Pepaxti is 40 mg on Day 1 of each 28-day treatment cycle. For patients with a body weight of 60 kg or less the recommended starting dose is 30 mg on Day 1 of each 28-day cycle.

1). The recommended dose of dexamethasone is 40 mg orally on Days 1, 8, 15 and 22 of each 28-day treatment cycle. For patients 75 years of age and older the recommended dose of dexamethasone is 20 mg. 1 and the corresponding Summary of Product Characteristics.

Dose modification for adverse reactions Pepaxti must be withheld if the neutrophil count is less than 1 × 109/L or the platelet count is less than 50 × 109/L. The recommended dose reduction and dosage modifications for adverse reactions of Pepaxti are presented in Table 1 and Table 2, respectively.

3 Table 1: Recommended dose reduction for adverse reactions of Pepaxti Dose reduction Dose* in patients with body weight greater than 60 kg Dose* in patients with body weight of 60 kg or less 40 mg 30 mg First 30 mg 20 mg Second 20 mg 15 mg Third 15 mg Permanently discontinue Pepaxti in patients who are unable to tolerate 15 mg Subsequent Permanently discontinue Pepaxti in patients who are unable to tolerate 15 mg - *Administered intravenously on Day 1 of each 28-day cycle.

4) Platelet count less than 50 × 109/L on an intended Pepaxti dosing day • Withhold Pepaxti and monitor platelet count weekly until platelet count is 50 × 109/L or greater. • Resume Pepaxti at 1 dose level lower. Absolute neutrophil count less than 1 × 109/L on an intended Pepaxti dosing day • Withhold Pepaxti and monitor neutrophil count weekly until neutrophil count is 1 × 109/L or greater.

• Resume Pepaxti at 1 dose level lower. 8) Grade 2 • Consider withholding Pepaxti until resolved to at least Grade 1 or baseline. • Consider resuming Pepaxti at 1 dose level lower. Grade 3 or 4 • Withhold Pepaxti until resolved to at least Grade 1 or baseline.

• Consider resuming Pepaxti at 1 dose level lower. 8). 4). Special populations Elderly No dose adjustment is recommended for elderly patients. 73 m2. 73 m2. 2). 2). There are insufficient data in patients with moderate or severe hepatic impairment to support a dose recommendation.

8. When the melphalan flufenamide metabolite melphalan is used in combination with lenalidomide and prednisone, and to a lesser extent in combination with thalidomide and prednisone, it has been linked to an increased risk of solid SPMs for elderly patients with newly diagnosed multiple myeloma.

Melphalan flufenamide is not indicated in combination with lenalidomide or thalidomide. Patients should be monitored closely before and during treatment for occurrence of SPM. 1). This is based on results from study OP-103 (OCEAN), a randomised phase 3 trial in patients with relapsed or refratory multiple myeloma following 2 to 4 lines of prior therapy and refractory to lenalidomide and the last line of therapy.

1; n=101), respectively. 0; n=145) on melphalan flufenamide/dexamethasone vs. 5; n=148) in the pomalidomide/dexamethasone arm. Myeloablative conditioning treatment The efficacy and safety of Pepaxti at doses required for myeloablation have not been studied in humans.

Pepaxti should not be used for conditioning treatment prior to stem cell transplantation. Renal impairment Since patients with renal impairment may have marked bone marrow suppression, these patients should be closely monitored. 2). Attenuated live vaccines A risk of severe illness that may lead to fatal outcome has been described with the metabolite melphalan in patients receiving attenuated live vaccines.

This risk is increased in patients who are already immunosuppressed by their underlying disease. An inactivated or mRNA based vaccine should be used when such a vaccine exists. 5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed with melphalan flufenamide.

2). 6 Fertility, pregnancy and lactation Women of childbearing potential/Contraception in males and females As with all cytotoxic treatments, male and female patients who use melphalan flufenamide should use effective and reliable contraceptive methods until six months after cessation of treatment.

Melphalan flufenamide can cause local tissue damage. 2). Thrombocytopenia Pepaxti may cause thrombocytopenia. 8). As thrombocytopenia may increase the risk for serious bleeding events, patients should be advised to contact a physician if signs or symptoms of bleeding and bruising occur.

Platelet counts should be monitored at baseline, during treatment, and as clinically indicated. Patients should be monitored more frequently during the first two months of treatment. Pepaxti should not be administered if the platelet count is less than 50 × 109/L.

Treatment should be withheld until platelet count is 50 × 109/L or greater (without recent transfusions) and resume treatment at one dose level lower. 2). Treating thrombocytopenia with transfusions and/or other treatments should be considered as clinically indicated.

Neutropenia Pepaxti may cause neutropenia. 8). As neutropenia may increase the risk for infections, patients should be advised to contact a physician if signs or symptoms of infection occur. Neutrophil count should be monitored at baseline, during treatment, and as clinically indicated.

Patients should be monitored more frequently during the first two months of treatment. Pepaxti should not be administered if absolute neutrophil count is less than 1 × 109/L. Treatment should be withheld until absolute neutrophil count is 1 × 109/L or greater and resume treatment at one dose level lower.

2). 2). 8). Red blood cell counts should be monitored at baseline, during treatment, and as clinically indicated. Patients should be monitored more frequently during the first two months of treatment. Treating anaemia with transfusions and/or erythropoietin should be considered as clinically indicated.

8). Patients should be closely monitored for signs of infection. Treating infections with antimicrobials should be considered as clinically indicated. 8). 2). 8). Patients with known risk factors for thromboembolism, including prior thrombosis, should be closely monitored.

1. 6).