Active Ingredient: Teclistamab
Teclistamab is indicated in combination with daratumumab for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Subcutaneous, 0.06 milligrams teclistamab per kilogram of body weight, one dose, over the duration of 2 days. Afterwards, subcutaneous, 0.3 milligrams teclistamab per kilogram of body weight, one dose, over the duration of 4 days. Afterwards, subcutaneous, 1.5 milligrams teclistamab per kilogram of body weight, one dose, over the duration of 1 week. Afterwards, subcutaneous, 1.5 milligrams teclistamab per kilogram of body weight, once weekly, one dose, over the duration of 6 weeks. Afterwards, subcutaneous, 3 milligrams teclistamab per kilogram of body weight, once every 2 weeks, one dose, over the duration of 16 weeks. Afterwards, subcutaneous, 3 milligrams teclistamab per kilogram of body weight, once every 4 weeks.
Pre-treatment medicinal products should be administered prior to each dose of teclistamab in the step-up dosing schedule (see below).
Teclistamab step-up dosing schedule should not be administered in patients with active infection (see Table 3).
Treatment with teclistamab should be initiated according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome. Due to the risk of cytokine release syndrome, patients should be instructed to remain within proximity of a healthcare facility, and monitored for signs and symptoms daily for 48 hours after administration of all doses within the teclistamab step-up dosing schedule.
Failure to follow the recommended doses or dosing schedule for initiation of therapy, or re-initiation of therapy after dose delays, may result in increased frequency and severity of adverse reactions related to mechanism of action, particularly cytokine release syndrome.
Teclistamab dosing schedule in Table 1 is for combination therapy with daratumumab.
Table 1. Teclistamab dosing schedule for combination therapy with daratumumab:
| Dosing schedulea | Week/Day | Doseb | |
| Day 1 | Daratumumab dosing only | ||
| Step-up dosing schedulec | Day 2d | Step-up dose 1 | 0.06 mg/kg |
| Day 4e | Step-up dose 2 | 0.3 mg/kg | |
| Day 8f | First treatment dose | 1.5 mg/kg | |
| Weekly dosing schedulec | Weeks 3 to 8g | Subsequent treatment doses | 1.5 mg/kg |
| Q2W (every two weeks) dosing schedulec | Weeks 9 to 24h | Subsequent treatment doses | 3 mg/kg |
| Q4W (every four weeks) dosing schedulec | Week 25 onwardsh | Subsequent treatment doses | 3 mg/kg |
a Teclistamab must be administered at least 3 hours after daratumumab for the first treatment dose and thereafter, teclistamab must be administered at least 15 minutes after daratumumab.
b Dose is based on actual body weight and must be administered subcutaneously.
c See Table 2 for recommendations on restarting teclistamab after dose delays.
d Step-up dose 1 must be administered 20 hours or more after daratumumab.
e Step-up dose 2 may be given between 2 to 7 days after Step-up dose 1,
f First treatment dose may be given between 2 to 7 days after Step-up dose 2. This is the first full treatment dose (1.5 mg/kg).
g Maintain a minimum of 5 days between 1.5 mg/kg treatment doses.
h Maintain a minimum of 12 days between 3 mg/kg treatment doses.
For dosing and administration instructions of daratumumab, please refer to the daratumumab solution for subcuteaneous injection Summary of Product Characteristics for monotherapy, except that dexamethasone (or equivalent) premedication should not be administered after the teclistamab step-up dosing schedule.
Patients should be treated with teclistamab until disease progression or unacceptable toxicity.
The following pre-treatment medicinal products must be administered 1 to 3 hours before each dose of the teclistamab step-up dosing schedule (see Table 1) to reduce the risk of cytokine release syndrome.
Administration of pre-treatment medicinal products may also be required prior to administration of subsequent doses of teclistamab for the following patients:
If a dose of teclistamab is delayed, therapy should be restarted based on the recommendations listed in Table 2 and teclistamab resumed according to the dosing schedule. Pre-treatment medicinal products should be administered as indicated in Table 2.
Table 2. Recommendations for restarting therapy with teclistamab after dose delay:
| Last dose administered | Duration of delay from the last dose administered | Action |
| Step-up dose 1 | More than 1 week (>7 days) | Restart teclistamab step-up dosing schedule at Step-up dose 1 (0.06 mg/kg)a. |
| Step-up dose 2 | More than 1 week to less than or equal to 4 weeks (8 days to ≤28 days) | Repeat Step-up dose 2 (0.3 mg/kg)a and continue teclistamab step-up dosing schedule. |
| More than 4 weeks (>28 days) | Restart teclistamab step-up dosing schedule at Step-up dose 1 (0.06 mg/kg)a. | |
| Any treatment doses | More than 1 week to less than or equal to 9 weeks (8 days to ≤63 days) | Continue teclistamab at last treatmentdose and schedule. |
| More than 9 weeks to less than or equal to 16 weeks (64 days to ≤112 days) | Restart teclistamab step-up dosing schedule at Step-up dose 2 (0.3 mg/kg)a. | |
| More than 16 weeks (>112 days) | Restart teclistamab step-up dosing schedule at Step-up dose 1 (0.06 mg/kg)a. |
a Pre-treatment medicinal products should be administered prior to teclistamab dose.
Treatment with teclistamab should be initiated according to the step-up dosing schedule in Table 1.
Combination therapy: Dose reductions of teclistamab during the step-up dosing and the first 1.5 mg/kg treatment dose are not recommended.
Refer to the daratumumab solution for subcutaneous injection Summary of Product Characteristics for information about dose modifications for daratumumab.
Dose delays may be required to manage toxicities related to teclistamab. Recommendations on restarting teclistamab after a dose delay are provided in Table 2.
Recommended actions after adverse reactions following administration of teclistamab are listed in Table 3.
Table 3. Recommended actions taken after adverse reactions following administration of teclistamab:
| Adverse reactions | Grade | Actions |
| Cytokine release syndromea | Grade 1 • Temperature ≥38°Cb | • Withhold teclistamab until adverse reaction resolves. • See recommendations for management of cytokine release syndrome. |
| Grade 2 • Temperature ≥38°Cb with either: • Hypotension responsive to fluids and not requiring vasopressors, or • Oxygen requirement of low- flow nasal cannulac or blow-by Grade 3 (Duration: less than 48 hours) • Temperature ≥38°Cb with either: • Hypotension requiring one vasopressor with or without vasopressin, or • Oxygen requirement of high- flow nasal cannulac, facemask, non-rebreather mask, or Venturi mask | • Withhold teclistamab until adverse reaction resolves. • See recommendations for management of cytokine release syndrome. • Administer pre-treatment medicinal products prior to next dose of teclistamab. • Monitor patient daily for 48 hours following the next dose of teclistamab. Instruct patients to remain within proximity of a healthcare facility during daily monitoring. | |
| Grade 3 (Recurrent or duration: more than 48 hours) • Temperature ≥38°Cb with either: • Hypotension requiring one vasopressor with or without vasopressin, or • Oxygen requirement of high- flow nasal cannulac, facemask, non-rebreather mask, or Venturi mask. Grade 4 • Temperature ≥38°Cb with either: • Hypotension requiring multiple vasopressors (excluding vasopressin), or • Oxygen requirement of positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation). | • Permanently discontinue therapy with teclistamab. • See recommendations for management of cytokine release syndrome. | |
| Immune effector cell-associated neurotoxicity syndrome (ICANS)d | Grade 1 | • Withhold teclistamab until adverse reaction resolves. • See recommendations for management of immune effector cell-associated neurotoxicity syndrome. |
| Grade 2 Grade 3 (First occurrence) | • Withhold teclistamab until adverse reaction resolves. • See recommendations for management of immune effector cell-associated neurotoxicity syndrome. • Monitor patient daily for 48 hours following the next dose of teclistamab. Instruct patients to remain within proximity of a healthcare facility during daily monitoring. | |
| Grade 3 (Recurrent) Grade 4 | • Permanently discontinue therapy with teclistamab. • See recommendations for management of immune effector cell-associated neurotoxicity syndrome. | |
| Infections | All Grades | • Do not administer teclistamab step-up dosing schedule in patients with active infection. Teclistamab step-up dosing schedule may proceed upon resolution of active infection. |
| Grade 3 Grade 4 | • Withhold subsequent treatment doses of teclistamab (i.e., doses administered after teclistamab step-up dosing schedule) until no evidence of an active infection. | |
| Haematologic toxicities | Absolute neutrophil count less than 0.5✕109/L | • Withhold teclistamab until absolute neutrophil count is 0.5✕109/L or higher. |
| Febrile neutropenia | • Withhold teclistamab until absolute neutrophil count is 1.0✕109/L or higher, and fever resolves. | |
| Haemoglobin less than 8 g/dL | • Withhold teclistamab until haemoglobin is 8 g/dL or higher. | |
| Monotherapy: Platelet count less than 25 000/μL Platelet count between 25 000/μL and 50 000/μL with bleeding Combination therapy: Platelet count less than 50 000/μL | Monotherapy • Withhold teclistamab until platelet count is 25 000/μL or higher and no evidence of bleeding. Combination therapy • Withhold teclistamab until platelet count is 50 000/μL or higher and no evidence of bleeding. | |
| Other adverse reactionse | Grade 3 Grade 4 | • Withhold teclistamab until adverse reaction improves to Grade 2 or better. |
a Based on American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS (Lee et al 2019).
b Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy (e.g., tocilizumab or corticosteroids).
c Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.
d Based on ASTCT grading for ICANS.
e Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.
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