Active Ingredient: Linvoseltamab
Linvoseltamab is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 5 milligrams linvoseltamab, 1 one dose, over the duration of 1 week. Afterwards, intravenous, 25 milligrams linvoseltamab, 1 one dose, over the duration of 1 week. Afterwards, intravenous, 200 milligrams linvoseltamab, once weekly, over the duration of 11 weeks. Afterwards, intravenous, 200 milligrams linvoseltamab, once every 2 weeks.
Pretreatment medicinal products in Table 1 should be administered to reduce the risk of CRS and/or IRR. Pretreatment medicinal products should be administered until two full doses are tolerated without CRS and/or IRR.
Table 1. Pretreatment medicinal products:
| Dose | Pretreatment medicinal products | Administration relative to linvoseltamab infusion |
|---|---|---|
| Step up dosing (including the 1st 200 mg dose) | 40 mg dexamethasone IV | 1 to 3 hours prior to infusion |
| Antihistamine (e.g., diphenhydramine 25 mg oral or IV) | 30 to 60 minutes prior to infusion | |
| Paracetamol (e.g., 500 to 1000 mg oral) | 30 to 60 minutes prior to infusion | |
| 2nd 200 mg dose | Dexamethasone | 1 to 3 hours prior to infusion |
| 40 mg dexamethasone IV in patients who experienced CRS and/or IRR with prior infusion | ||
| 10 mg dexamethasone IV in patients who did not experience CRS and/or IRR with prior infusion | ||
| Antihistamine (e.g., diphenhydramine 25 mg oral or IV) | 30 to 60 minutes prior to infusion | |
| Paracetamol (e.g., 500 to 1000 mg oral) | 30 to 60 minutes prior to infusion | |
| Subsequent 200 mg doses | • If the patient experienced CRS and/or IRR with the prior infusion, repeat pretreatment medicinal products as described above for the 2nd 200 mg dose. • Once the 200 mg dose is tolerated without CRS and/or IRR: o If the patient received 40 mg dexamethasone IV with the prior infusion, step down to 10 mg dexamethasone IV and continue other pretreatment medicinal products as described above. o If the patient received 10 mg dexamethasone IV with the prior infusion, discontinue all pretreatment medicinal products. | |
Prophylactic treatment per local institutional guidelines for Pneumocystis jirovecii pneumonia (PJP) and herpes simplex and zoster viruses is recommended for all patients. Prophylactic antimicrobials and anti-virals, including prophylaxis against cytomegalovirus (CMV) infection, should be considered based on local institutional guidelines.
The recommended step-up treatment doses, full treatment dose, and treatment frequency are presented in Table 2. Each dose should only be administered if the previous dose is tolerated.
All patients should be monitored for signs and symptoms of potential CRS, IRR, and ICANS during administration and for 24 hours after the end of the infusion of the first step‑up treatment dose. Patients should be instructed to remain with a caregiver within close proximity of the qualified treatment centre for 24 hours after the first step-up treatment dose.
Patients who have experienced CRS, IRR, a neurologic adverse reaction, or any grade ≥ 2 adverse event, with the first step-up treatment dose administration should be monitored during administration and for 24 hours after the administration of the second step-up treatment dose and should be instructed to remain with a caregiver within close proximity of the qualified treatment centre for 24 hours.
Table 2. Recommended posology:
| Dosing schedule | Daya | Linvoseltamab dose | |
|---|---|---|---|
| Step-up dosing schedule | Week 1 Day 1 | Step-up treatment dose 1 | 5 mg |
| Week 2 Day 1 | Step-up treatment dose 2 | 25 mg | |
| Week 3 Day 1 | First full treatment dose | 200 mg | |
| Weekly dosing schedule | Week 4 to Week 13 for 10 treatment doses | Full treatment doses | 200 mg |
| Every 2 weeks dosing schedule | Week 14 and every 2 weeks thereafter | Full treatment doses | 200 mg |
| Patients who have received at least 17 doses of 200 mg and have confirmed response of very good partial response (VGPR) or better per international myeloma working group (IMWG) criteria at or after Week 24b | |||
| Every 4 weeks dosing schedule | At week 24 or after and every 4 weeks thereafter | Treatment doses | 200 mg |
a Weekly doses should be at least 5 days apart.
b Patients who have not achieved VGPR or better at Week 24 should continue receiving linvoseltamab every 2 weeks.
Treatment should be continued until disease progression or unacceptable toxicity.
If a dose is missed, it should be administered as soon as possible based on Table 3.
Table 3. Recommendations for restarting therapy with linvoseltamab after a missed dose:
| Last dose administered | Time since the last dose administereda | Action for next dose. |
|---|---|---|
| 5 mg | ≤ 14 days | Administer 25 mg |
| > 14 days | Restart step-up dosing from 5 mg | |
| 25 mg | ≤ 14 days | Administer 200 mg |
| > 14 days and ≤ 28 days | Restart step-up dosing from 25 mg | |
| > 28 days | Restart step-up dosing from 5 mg | |
| 200 mg | ≤ 49 days | Administer 200 mg |
| > 49 days | Restart step-up dosing from 5 mg |
NOTE: Administer pretreatment medicinal products as per Table 1.
a Consider benefit-risk of restarting linvoseltamab in patients who require a dose delay of more than 30 days.
Linvoseltamab should be administered as an intravenous infusion through a dedicated infusion line. It is recommended to use a 0.2-micron to 5-micron polyethersulfone (PES) filter.
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