Besponsa

Instructions for Inotuzumab Ozogamicin
Common name: Inotuzumab Ozogamicin Trade name: Besponsa
Full names: Inotuzumab Ozogamicin, Besponsa
Indications:
Applicable to the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia in adults.
Dosage:
Initiate medical therapy with corticosteroids, antipyretics, and antihistamines before all infusions.
Based on the drug treatment response, the dosage is divided into the first cycle and subsequent cycles:
First cycle: 0.8mg/㎡ on the 1st day, 0.5mg/㎡ on the 8th and 15th days, and 21 days is a cycle.
Follow-up cycles: The patient achieves remission: 0.5 mg/㎡ on days 1, 8, 15, and 28 days as one cycle. The patient did not achieve remission: 0.8 mg/㎡ on the 1st day, 0.5 mg/㎡ on the 8th and 15th days, and a cycle of 28 days.
Adverse reactions:
>10%:
Central nervous system: fatigue (35%), headache (28%), chills (11%)
Endocrine and metabolism: increased γ-glutamyl transferase (21%-67%), hyperuricemia (4%-16%)
Gastrointestinal tract: increased serum lipase (9%-32%), nausea (31%), abdominal pain Pain (23%), diarrhea (17%), constipation (16%), vomiting (15%), elevated serum amylase (5%-15%), stomatitis (13%), decreased appetite (12%)
Hematology and tumors: thrombocytopenia (51%; Grade 3: 14%; Grade 4: 28%), neutropenia (49%; Grade 3: 20%-49%; Grade 4: 27%) ), anemia (36%; grade ≥3: 24%), leukopenia (35%; grade ≥3: 33%), bleeding (grade ≥3: 5%-33%), febrile neutropenia (26%; grade ≥3: 26%), lymphopenia (18%; grade ≥3: 16%)
Liver: serum AST (aspartate aminotransferase) increased (71%), serum alkaline phosphatase increased High (13%-57%), elevated serum ALT (alanine aminotransferase) (49%), elevated serum aminotransferase (26%), hepatic veno-occlusive disease (≤23%), hyperbilirubinemia (21%), hepatotoxicity (14%)
Infection: infection (48%)
Respiratory tract: epistaxis (15%)
Others: fever (32%)
1% - 10%:
Cardiovascular: Prolonged QT interval on electrocardiogram (1%)
Gastrointestinal tract: Abdominal distension (6%)
Hematology and neoplasms: Bone marrow failure (2%; includes bone marrow failure, febrile bone marrow aplasia), tumor lysis syndrome (2%)
Liver: Ascites (4%)
Immunology: Antibody development (Anti-intuzumab antibodies: 3%)
Others: Infusion-related reactions (2%; Grade 2: 2%; includes anaphylaxis)
Undefined frequency:
Infections: bacterial infections, fungal infections, viral infections

Contraindications:
Hypersensitivity to intuzumab or any formulation component.

Precautions:
Myelosuppression: Hematologic toxicities, including thrombocytopenia and neutropenia (including grade 3 and 4). More than a quarter of patients develop neutropenia, which can be life-threatening. For patients who are in complete remission (CR) or hematological recovery incomplete (CRi) at the end of treatment, in some patients, the platelet recovery time (>50000/mm³) after the last dose is more than 45 days. Complications related to myelosuppression (including infections and bleeding events) were observed. Monitor complete blood counts before each dose and monitor for signs and symptoms of myelosuppression during treatment; treatment interruption, dose reduction, or permanent discontinuation may be necessary.
Bleeding: Bleeding events related to thrombocytopenia have been reported, including Grade 3 or 4 bleeding events and Grade 1 and Grade 5 (fatal) intra-abdominal bleeding. The most common bleeding event is epistaxis. Monitor for signs and symptoms of bleeding/bleeding during treatment; treatment interruption, dose reduction, or permanent discontinuation may be necessary.
Hypersensitivity: Hypersensitivity reactions have been reported.
Infections: Infections, including serious infections (some life-threatening or fatal), have been reported in nearly half of patients treated with intuzumab. Fatal infections, including pneumonia, neutropenia, sepsis, septic shock, and pseudosepsis; bacterial, viral, and fungal infections occur. Monitor for signs and symptoms of infection during treatment. Use prophylactic anti-infective medications and perform surveillance tests during and after treatment. Severe infections may require treatment interruption, dose reduction, or permanent discontinuation of treatment.
Infusion Reactions: Grade 2 infusion-related reactions have been reported in a small proportion of patients. Infusion reactions (such as fever, chills, rash, dyspnea) usually occur within the first cycle shortly after the end of the infusion and disappear under natural or drug treatment. Pretreat with corticosteroids, antipyretics, and antihistamines before administration. Monitor closely for potential reactions during the infusion and for at least 1 hour after the end of the infusion. If an infusion reaction occurs, interrupt the infusion and handle appropriately. Depending on severity, consider stopping the infusion or administering corticosteroids and antihistamines. If serious or life-threatening infusion reaction occurs, permanently discontinue the drug.
QT interval prolongation: Obtain an electrocardiogram (ECG) and electrolytes at baseline and monitor during treatment. More frequent monitoring should be performed when using mediators known to prolong the QT interval.
Fetal Toxicity: Can cause fetal harm. It is recommended that women with potential fetal reproductive risks use effective contraceptive methods.

Storage:
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze.
Place the vial in the original carton to protect it from light.

Mechanism of action:
Ointuzumab is a CD22-directed antibody-drug conjugate (ADC). Intuzumab recognizes human CD22. The small molecule N-acetyl γ-calicheamicin is a cytotoxic agent covalently linked to an antibody through a linker. Non-clinical data indicate that the anti-cancer activity of intuzumab is due to the binding of ADC to CD22-expressing tumor cells, subsequent internalization of the ADC-CD22 complex, and cleavage of the N-acetyl-γ-calicheamicin dicarboxylic acid hydrazide hydrolytic linker. Activation of N-acetyl-γ-calicheamicin dimethylhydrazide induces double-stranded DNA breaks and subsequently induces cell cycle arrest and apoptotic cell death.
Safety and Efficacy:
The phase 3 INO-VATE ALL trial is a randomized, open-label, international, multi-center study that enrolled 326 adult patients with relapsed or refractory B-cell ALL (acute lymphoblastic leukemia) and compared the efficacy and safety of intuzumab with standard chemotherapy. Ointuzumab improved multiple efficacy indicators, including hematological response rate, MRD (minimal residual disease in leukemia) negative rate and stem cell transplant rate.
For patients treated with intuzumab, the complete response rate (CR/CRI)* under complete remission/incomplete blood recovery (CR/CRI)* was 81%, while the complete response rate for patients treated with chemotherapy was only 29%. Among all patients who achieved CR/CRi (complete response/complete response rate with incomplete hemogram recovery), those who received intuzumab also had a higher rate of minimal residual disease (MRD) negativity (78%) compared to those who received chemotherapy (28%). Forty-eight percent of patients who received intuzumab underwent hematopoietic stem cell transplantation (HSCT), compared with 22% of patients who received chemotherapy. The median overall survival (OS) was 7.7 months for patients who received intuzumab and 6.2 months for those who received chemotherapy.