Inotuzumab ozogamicin (Besponsa) is an antibody-drug conjugate targeting CD22, indicated for the treatment of relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia in adults and children aged 1 year and older.
How to Administer Inotuzumab Ozogamicin (Besponsa)
Administration Route and Pretreatment
Inotuzumab ozogamicin is for intravenous infusion only; administration via other routes is prohibited.
To prevent infusion-related reactions, patients must receive pretreatment before each dose, including the use of corticosteroids, antipyretic analgesics, and antihistamines.
During the infusion and for at least 1 hour after the infusion is completed, patients must be closely monitored for symptoms such as fever, chills, rash, or dyspnea.
Recommended Dosing Regimen
Cycle 1: The total dose is 1.8 mg/m², administered as 3 intravenous infusions: 0.8 mg/m² on Day 1, 0.5 mg/m² on Day 8, and 0.5 mg/m² on Day 15. The cycle length is 21 days. If the patient achieves complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), and/or needs to recover from toxicity, the cycle may be extended to 28 days.
Subsequent cycles: If the patient has achieved CR or CRi, the total dose for subsequent cycles is 1.5 mg/m², also administered in 3 doses (0.5 mg/m² each on Days 1, 8, and 15), with a cycle length of 28 days.
If the patient has not achieved CR or CRi, the total dose for subsequent cycles remains 1.8 mg/m², administered in the same manner as Cycle 1, with a cycle length of 28 days. If CR or CRi is still not achieved after 3 cycles, treatment should be considered discontinued.
Number of Treatment Cycles
For patients planning to undergo hematopoietic stem cell transplantation, 2 treatment cycles are recommended.
Patients who have not achieved CR/CRi and have positive minimal residual disease may consider a 3rd cycle. Non-transplant patients may receive a maximum of 6 treatment cycles.
Preparation and Administration Procedures
This drug is a lyophilized powder and must first be reconstituted with 4 mL of sterile water for injection. Gently swirl until completely dissolved; shaking is prohibited.
The reconstituted solution should be clear to opalescent and colorless to slightly yellow.
Based on the calculated dose, draw the required volume of the reconstituted solution and further dilute it with 0.9% sodium chloride injection.
The diluted solution must be protected from light and the infusion must be completed within 8 hours after reconstitution (including no more than 4 hours from reconstitution to dilution, plus a 1-hour infusion time).
Infusion must be administered using an intravenous infusion pump, over a period of 1 hour.
Dosage Adjustment of Inotuzumab Ozogamicin (Besponsa)
For Hematologic Toxicity
Myelosuppression (e.g., neutropenia, thrombocytopenia) often occurs during treatment.
If the absolute neutrophil count (ANC) is ≥1.0×10⁹/L or the platelet count is ≥50×10⁹/L before the start of the next cycle, but a decrease occurs after treatment, the next cycle should be interrupted until the counts recover to the above levels.
If persistent low counts last for more than 28 days and are suspected to be drug-related, permanent discontinuation of the drug is required.
For Non-Hematologic Toxicity
Hepatotoxicity: If hepatic veno-occlusive disease (VOD) or other severe hepatotoxicity occurs, permanent drug discontinuation is required. If total bilirubin >1.5×upper limit of normal (ULN) and AST/ALT >2.5×ULN, administration should be interrupted until recovery. If recovery is not possible, permanent discontinuation is required.
Infusion-related reactions: If a reaction occurs, the infusion should be interrupted and symptomatic treatment provided. Severe or life-threatening reactions require permanent drug discontinuation.
Other non-hematologic toxicities: If Grade ≥2 toxicity occurs, treatment should be interrupted until recovery to Grade 1 or baseline level.
Impact of Administration Interruption Duration
Interruption <7 days: The next dose in the cycle may be interrupted, but an interval of at least 6 days between the two doses must be ensured.
Interruption ≥7 days: The next dose within the cycle should be skipped.
Interruption ≥14 days: After resumption, the total dose for subsequent cycles should be reduced by 25%; if intolerance persists, the number of doses per cycle may be reduced to 2.
Interruption >28 days: Consider permanent discontinuation of the drug.
Administration of Inotuzumab Ozogamicin (Besponsa) in Special Populations
Patients with Hepatic Impairment
For patients with mild hepatic impairment (total bilirubin ≤1.5×ULN and AST/ALT ≤2.5×ULN), no adjustment to the initial dose is required.
Limited safety data are available for patients with pretreatment total bilirubin >1.5×ULN and/or AST/ALT >2.5×ULN. Liver function indicators must return to the above range before each dose; otherwise, administration should be interrupted.
If recovery is not possible, permanent discontinuation is required.
Pregnant and Lactating Women
Pregnancy: Based on its mechanism of action and animal study data, this drug may cause harm to the fetus.
Women of childbearing potential should be advised to use effective contraception during treatment and for 8 months after the last dose.
Male patients should advise their female partners to use effective contraception during treatment and for 5 months after the last dose.
Lactation: Women are advised not to breastfeed during treatment and for 2 months after the last dose.
