BESPONSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BESPONSA (BESPONSA).
Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate (ADC) consisting of a humanized anti-CD22 monoclonal antibody conjugated to N-acetyl-gamma-calicheamicin dimethylhydrazide, a cytotoxic calicheamicin derivative. Upon binding to CD22-expressing tumor cells, the ADC is internalized, and calicheamicin is released intracellularly, causing DNA double-strand breaks and subsequent cell death.
| Metabolism | Metabolized via non-enzymatic reduction and enzymatic hydrolysis. Not primarily metabolized by CYP enzymes. |
| Excretion | Primarily hepatic metabolism, with drug-related material excreted in feces (84.5%) and urine (12.4%) over 30 days. Unchanged drug is minimal in urine. |
| Half-life | Terminal elimination half-life of 14.2 days for total calicheamicin equivalents; 2.0 days for unconjugated calicheamicin. |
| Protein binding | Binding to human plasma proteins is approximately 97% for total drug-related calicheamicin; primarily binds to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 13.3 L (0.19 L/kg for a 70 kg adult), indicating extensive extravascular distribution. |
| Bioavailability | Administered only intravenously; bioavailability is 100% by IV route. |
| Onset of Action | Median time to first response (CR/CRi) approximately 2.3 months (range 0.3–5.6 months) in clinical trials (IV administration). |
| Duration of Action | Median duration of remission (CR/CRi) was 8.3 months in relapsed/refractory ALL; duration may vary based on disease status and subsequent therapy. |
| Brand Substitutes | Inonza 1mg Injection |
9 mg/m2 intravenously on Days 1, 8, and 15 of a 28-day cycle for up to 3 cycles.
| Dosage form | POWDER, FOR INJECTION SOLUTION, LYOPHILIZED POWDER |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Safety data insufficient for GFR <30 mL/min. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) impairment. Not recommended in severe (Child-Pugh C) impairment. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required. Increased monitoring for hepatotoxicity and infections due to age-related physiological changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BESPONSA (BESPONSA).
| Breastfeeding | It is unknown whether inotuzumab ozogamicin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants, breastfeeding should be discontinued during treatment with BESPONSA and for at least 2 months after the last dose. The M/P ratio is not available. |
| Teratogenic Risk | BESPONSA (inotuzumab ozogamicin) is classified as Pregnancy Category D. There is positive evidence of human fetal risk based on human data. Embryotoxicity, including severe fetal malformations and spontaneous abortion, has been reported. Use during pregnancy, particularly in the first trimester, is contraindicated. Adequate contraception is required for women of childbearing potential during treatment and for at least 8 months after the last dose. |
■ FDA Black Box Warning
Hepatotoxicity, including fatal and life-threatening veno-occlusive disease (VOD) and hepatic sinusoidal obstruction syndrome (SOS). Risk is higher in patients who undergo hematopoietic stem cell transplantation (HSCT) after treatment with Besponsa.
| Serious Effects |
["None known."]
| Precautions | ["Hepatotoxicity: Monitor liver function tests; hold or discontinue if signs of VOD/SOS occur.","Post-HSCT non-relapse mortality: Increased risk in patients with VOD, bilirubin > upper limit of normal, or age ≥ 45 years.","Bone marrow suppression: Monitor complete blood counts; manage with growth factors.","Infusion-related reactions: Premedicate and monitor during infusion.","Increased risk of infections: Monitor for signs of infection.","Vaccinations: Avoid live vaccines during treatment."] |
| Food/Dietary | No specific food restrictions. However, due to risk of liver toxicity, patients should avoid excessive alcohol consumption and discuss any hepatotoxic medications or supplements with their healthcare provider. |
Loading safety data…
| Fetal Monitoring | Monitor complete blood counts, liver function tests (including bilirubin, AST, ALT), and signs/symptoms of veno-occlusive liver disease (VOD). During pregnancy, perform serial fetal ultrasound to assess for growth and anomalies. In the postpartum period, monitor for hepatic toxicity and evidence of VOD. |
| Fertility Effects | BESPONSA may impair fertility in both males and females. Reversible amenorrhea has been reported. The mechanism involves targeted cytotoxicity against CD22-positive B cells, which may affect ovarian and testicular function. Long-term effects on fertility are unknown. |
| Clinical Pearls | BESPONSA (inotuzumab ozogamicin) is a CD22-directed antibody-drug conjugate for relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL). Monitor for veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), especially in patients who have undergone or will undergo hematopoietic stem cell transplantation (HSCT). Premedicate with corticosteroids, antipyretics, and antihistamines to mitigate infusion-related reactions. Administer at the recommended dose based on the first cycle (0.8 mg/m² on Day 1, 0.5 mg/m² on Days 8 and 15) and subsequent cycles (0.5 mg/m² on Days 1, 8, 15). Discontinue if VOD/SOS occurs. Monitor liver function tests and bilirubin closely. |
| Patient Advice | This drug may cause liver problems, including a serious condition called veno-occlusive disease. Notify your doctor immediately if you experience yellowing of skin or eyes, dark urine, right upper abdominal pain, or unexplained swelling. · You may experience infusion-related reactions; symptoms include fever, chills, rash, or difficulty breathing during or after the infusion. · This medication can lower your blood cell counts, increasing risk of infection, bleeding, or anemia. Report fever, bruising, or unusual tiredness. · Avoid pregnancy during treatment; use effective contraception. Notify your doctor if you are breastfeeding. · Do not receive live vaccines during treatment. |