What is Besponsa?

Besponsa (inotuzumab ozogamicin) is a prescription-only medicine manufactured by Pfizer Inc. It is an antibody-drug conjugate that is used for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Besponsa is recommended under the NCCN Clinical Practice Guidelines in Oncology, but it has not been tested or proven to work for children under the age of 18.

How does Besponsa work?

Besponsa is approved to treat acute lymphoblastic leukemia (ALL). In ALL, B-cells are dividing and growing faster than they should be. As they grow, the B-cells build up in the bone marrow and then spread to the blood and other parts of the body, causing leukemia. The active ingredient in Besponsa, inotuzumab ozogamicin, is a monoclonal antibody (mAb) that works against (ALL) by delivering an anti-tumor antibiotic called calicheamicin to the cancer cells, causing them to die.

What doses of Besponsa are available?

Besponsa comes in a single-dose vial as 0.9 mg lyophilized powder (white or off-white in color). It is then used for reconstitution and further dilution. Everyone being treated with Besponsa first goes through a 21-day cycle of three infusions, known as Cycle 1. You will receive 0.8 mg/m^2 on Day 1, 0.5 mg/m^2 on Day 8, and 0.5 mg/m^2 on Day 15.

After Cycle 1, your subsequent cycles will change depending on whether you have achieved complete remission or complete remission with incomplete hematologic recovery(CR/CRi), or neither. If a CR or CRi has been achieved, you will take a dose of 0.5 mg/m^2 on days 1, 8, and 15 of your next cycle.

If after Cycle 1 you have not achieved a CR or CRi, your next cycle will consist of a dose of 0.8mg/m^2 on day 1 and then a dose of 0.5 mg/m^2 on days 8 and 15.

No one should complete more than six cycles. Your healthcare provider will decide what treatment cycle is best for you.

How do you use Besponsa?

Besponsa should only be used as prescribed by your healthcare provider. Make sure to read the medication guide and full prescribing information before taking Besponsa.

Prior to all infusions, you must pre-medicate with an antipyretic, corticosteroid, and antihistamine. Besponsa is for intravenous use only in outpatient settings. The infusion usually takes around one hour. After the infusion, you most likely will be observed for about an hour to monitor for any negative infusion-related reactions.

You may have to use Besponsa by itself or with a tyrosine kinase inhibitor for Philadelphia chromosome-positive disease. See the section on dosing for more information on dosing cycles.

What are the side effects of Besponsa?

The most common side effects of Besponsa in clinical trials compared to placebo include:

Thrombocytopenia (low platelet count)
Infection
Neutropenia (low count of a specific white blood cell)
Leukopenia (drop in white blood cell count)
Anemia
Hemorrhage
Fatigue
Nausea
Pyrexia (fever)
Febrile neutropenia (fever during neutropenia)
Headache
Abdominal pain
Transaminases increased
Hyperbilirubinemia (build-up of bilirubin, causing jaundice)

Rarely, Besponsa may cause some serious adverse reactions. All of the following adverse reactions were found through a study called INO-VATE. INO-VATE compared Besponsa to the investigator’s choice of chemotherapy in 326 adult patients with relapsed or refractory B-cell precursor ALL. The efficacy of Besponsa was found on the basis and duration of whether patients reached CR, as well as the proportion of minimal residual disease (MRD)-negative CR and resolution of any extramedullary disease (EMD). In INO-VATE, they found the following potentially severe side effects of Besponsa:

Hepatic veno-occlusive disease (VOD)
- After infusions, monitor for signs of VOD, including hepatomegaly, elevations in total bilirubin, rapid weight gain, and ascites.
- The risk of VOD is higher if you underwent a hematopoietic stem cell transplant (HSCT) after Besponsa treatment. If you are having an HSCT, talk to your doctor about what treatment plan is best for you.
Increased risk of post-transplant non-relapse mortality.
Myelosuppression (lower than normal red and white blood cell count as well as platelet count).
- Myelosuppression can lead to anemia, thrombocytopenia, neutropenia, and other side effects.
- Monitor for signs of myelosuppression, including infection and bleeding.
Infusion-related reactions.
- It is important to be monitored for up to an hour after infusion to see how your body reacts to Besponsa.
QT interval prolongation.
- Symptoms include fast, erratic, and sometimes dangerous heartbeats.
Embryo-fetal toxicity.
- Besponsa may impair fertility.
- Contraception should be used in both male and female patients during and for eight months after the last dose of Besponsa.

Contact your healthcare professional for medical advice about any possible adverse events you experience while taking Besponsa. You can report your adverse effects to the Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch.

Besponsa drug interactions

When Besponsa is taken with other prescription drugs, over-the-counter medications, vitamins, and supplements, it may change how they work or increase the frequency or severity of side effects. Some drug interactions with Besponsa include:

Any medicinal products that prolong the QT interval.
- Administer Besponsa with caution if you are taking another medication that might increase the risk the QT interval prolongation. Talk to your doctor about possible alternatives.

Boxed warnings

Hepatotoxicity is a risk. This includes fatal and nonfatal hepatic venoocclusive disease (VOD), or sinusoidal obstruction syndrome (SOS).

There is also an increased risk of post-hematopoietic stem cell transplant (HSCT) non-relapse mortality.

Hepatotoxicity can be fatal. Life-threatening VOD has happened in people who have had all types of relapsed or refractory acute lymphoblastic leukemia. The risk of VOD is greater in people who have had certain HSCT regimens after Besponsa treatment.

Other risk factors of VOD with Besponsa include prior or ongoing liver disease, older age, prior HSCT, more Besponsa treatment cycles, and later salvage lines.

Besponsa precautions

You should be sure that your healthcare provider is aware of all your medical conditions, including if you have:

Liver problems or a history of liver problems.
An infection.
Heart problems, including a QT prolongation event.
A pregnancy, plan to become pregnant, or are breastfeeding.
- You may need to supply a pregnancy test before taking Besponsa.
- It is recommended to stop breastfeeding while taking Besponsa and for two months after your last dose.
- See the section on serious adverse reactions for more information about embryo-fetal toxicity.
Experienced adverse effects during or after Besponsa treatment.