Active Ingredient: Glofitamab
Glofitamab in combination with gemcitabine and oxaliplatin is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) who are ineligible for autologous stem cell transplant (ASCT).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 2.5 milligrams glofitamab, one dose, over the duration of 7 days. Afterwards, intravenous, 10 milligrams glofitamab, one dose, over the duration of 7 days. Afterwards, intravenous, 30 milligrams glofitamab, one dose, over the duration of 21 days. This step is repeated 11 times.
All patients in study NP30179 and in study GO41944 (STARGLO) received a single 1 000 mg dose of obinutuzumab as pre-treatment on Cycle 1 Day 1 (7 days prior to initiation of glofitamab treatment) to lower the circulating and lymphoid B cells.
Obinutuzumab was administered as an intravenous infusion at 50 mg/h. The rate of infusion was escalated in 50 mg/h increments every 30 minutes to a maximum of 400 mg/h.
Refer to the obinutuzumab prescribing information for complete information on premedication, preparation, administration and management of adverse reactions of obinutuzumab.
Glofitamab should be administered to well-hydrated patients. Recommended premedication for CRS is outlined in Table 1.
Table 1. Premedication before glofitamab infusion:
| Treatment cycle (Day) | Patients requiring premedication | Premedication | Administration |
|---|---|---|---|
| Cycle 1 (Day 8, Day 15); Cycle 2 (Day 1); Cycle 3 (Day 1) | All patients | 20 mg intravenous dexamethasone1 | Completed at least 1 hour prior to glofitamab infusion |
| Oral analgesic / anti-pyretic2 | At least 30 minutes before glofitamab infusion | ||
| Anti-histamine3 | |||
| All subsequent infusions | All patients | Oral analgesic / anti-pyretic2 | At least 30 minutes before glofitamab infusion |
| Anti-histamine3 | |||
| Patients who experienced CRS with the previous dose | 20 mg intravenous dexamethasone1,4 | Completed at least 1 hour prior to glofitamab infusion |
1 If patient has an intolerance to dexamethasone or dexamethasone is unavailable, administer 100 mg prednisone/prednisolone or 80 mg methylprednisolone.
2 For example, 1 000 mg paracetamol.
3 For example, 50 mg diphenhydramine.
4 To be administered in addition to the premedication required for all patients.
Glofitamab dosing begins with a step-up dosing schedule (which is designed to decrease the risk of CRS), leading to the recommended dose of 30 mg.
Glofitamab must be administered as an intravenous infusion according to the dose step-up schedule leading to the recommended dose of 30 mg (as shown in Table 2), after completion of pre-treatment with obinutuzumab on Cycle 1 Day 1.
Glofitamab is given in combination with gemcitabine and oxaliplatin at Cycles 1-8 and as monotherapy at Cycles 9-12. Each cycle is 21 days.
Table 2. Glofitamab dose step-up schedule in combination with gemcitabine and oxaliplatin for patients with relapsed or refractory DLBCL:
| Treatment cycle, Day | Dose of glofitamab (duration of infusion) | Dose of gemcitabine | Dose of oxaliplatin | |
|---|---|---|---|---|
| Cycle 1 (Pre-treatment and step-up dose) | Day 1 | Pre-treatment with obinutuzumab 1000 mga | ||
| Day 2 | – | 1000 mg/m²b | 100 mg/m²b | |
| Day 8 | 2.5 mg (4 hours)c | – | – | |
| Day 15 | 10 mg (4 hours)c | |||
| Cycle 2 | Day 1 | 30 mg (4 hours)c,d | 1000 mg/m²b,d | 100 mg/m²b,d |
| Cycle 3 to 8 | Day 1 | 30 mg (2 hours)d,e | 1000 mg/m²b,d | 100 mg/m²b,d |
| Cycle 9 | to 12 Day 1 | 30 mg (2 hours)e | – | – |
a Refer to "Pre-treatment with obinutuzumab" described above.
b Cycles 1-8: Administer gemcitabine before oxaliplatin.
c For patients who experience CRS with their previous dose of glofitamab, the time of infusion may be extended up to 8 hours.
d Cycles 2-8: Administer glofitamab before gemcitabine and oxaliplatin. Gemcitabine and oxaliplatin may be given on Day 1 or 2.
e Infusion time may be shortened to 2 hours at the discretion of the treating physician, if the previous infusion was well tolerated. If the patient experienced CRS with a previous dose, the duration of infusion should be maintained at 4 hours.
When glofitamab is given in combination with gemcitabine and oxaliplatin, patients must be monitored for signs and symptoms of potential CRS during all glofitamab infusions and for 4 hours after completion of the first glofitamab dose (2.5 mg on Cycle 1 Day 8).
Patients who experienced Grade ≥2 CRS with their previous infusion should be monitored after completion of the infusion.
All patients must be monitored for signs and symptoms of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) following glofitamab administration.
All patients must be counselled on the risk, signs and symptoms of CRS and ICANS and advised to contact the healthcare provider immediately should they experience signs and symptoms of CRS and/or ICANS at any time.
Treatment with glofitamab in combination with gemcitabine and oxaliplatin is recommended for 8 cycles, followed by 4 cycles of glofitamab monotherapy for a maximum of 12 cycles of glofitamab in total or until disease progression or unmanageable toxicity, whichever occurs first. Each cycle is 21 days.
During step-up dosing (weekly dosing):
After Cycle 2 (30 mg dose):
It must be administered as an intravenous infusion through a dedicated infusion line.
Glofitamab must not be administered as an intravenous push or bolus.
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