Oecabtagene Autoleucel

Obecabtagene autoleucel is a prescription medication indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

• Obecabtagene autoleucel is available under the following different brand names: Aucatzyl.

Common side effects of Obecabtagene autoleucel include:

• fever
• nausea
• diarrhea
• infections
• headache
• muscle or joint pain
• fatigue or feeling very tired
• low blood pressure (dizziness or light-headedness, headache, fatigue, shortness of breath)
• fast irregular heartbeat
• confusion
• difficulty speaking or slurred speech
• low white blood cells (can occur with a fever)
• bleeding

Serious side effects of Obecabtagene autoleucel include:

• cytokine release syndrome
• immune effector cell-associated neurotoxicity syndrome 
• neurologic toxicities
• t-cell malignancies

Rare side effects of Obecabtagene autoleucel include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Infusion, cell suspension

• 410 x 106 CD19 CAR-positive viable T cells (total dose)
• Supplied in 3-5 patient-specific infusion bags
• Blue bag
  • 10 × 106 CAR-positive viable T cells (10 mL in 50 mL infusion bag)
• Orange bag(s)
  • 100 x 106 CAR-positive viable T cells (10-20 mL in 1 or more 50 mL infusion bags)
  • 100 x 106 CAR-positive viable T cells (30-70 mL in 250 mL infusion bag)
• Red bag(s)
  • 300 x 106 CAR-positive viable T cells (30-70 mL in 1 or more 250 mL infusion bag)

Acute lymphoblastic leukemia

Adult dosage

• 410 x 106 CD19 CAR-positive viable T cells IV given as 2 split doses on days 1 and 10
• Infuse 3 days (+/- 1 day) after completion of lymphodepleting chemotherapy, allowing a minimum 48-hours washout
• Select the appropriate dosing regimen based on the patient’s bone marrow assessment (Bone Marrow Blast) results
• Premedicate with acetaminophen approximately 30 min before the dose
• Bone Marrow Blast of more than 20%
• Day 1
  • 10 × 106 CAR-positive viable T cells IV via syringe
• Day 10 (+/- 2 days)
  • 100 × 106 CAR-positive viable T cells IV via infusion bag, and
  • 300 × 106 CAR-positive viable T cells IV via infusion bag
• Bone Marrow Blast of 20% and less
• Day 1
  • 100 × 106 CAR-positive viable T cells IV via infusion bag
• Day 10 (+/- 2 days)
  • 10 × 106 CAR-positive viable T cells IV via syringe, and
  • 300 × 106 CAR-positive viable T cells IV via infusion bag

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Obecabtagene autoleucel has no noted severe interactions with any other drugs
• Obecabtagene autoleucel has no noted serious interactions with any other drugs
• Obecabtagene autoleucel has no noted moderate interactions with any other drugs
• Obecabtagene autoleucel has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Obecabtagene autoleucel?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Obecabtagene autoleucel?”

Cautions

• Cytokine release syndrome (CRS) 
  • CRS occurred in patients receiving obecabtagene autoleucel.
  • Do not administer obecabtagene autoleucel to patients with active infection or inflammatory disorders. 
  • Before administering obecabtagene autoleucel, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS
  • Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.
  • At the first sign of CRS, immediately evaluate the patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines
• Neurologic Toxicities
  • Neurologic toxicities including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which were fatal or life-threatening, occurred following treatment with obecabtagene autoleucel
• ICANS
  • ICANS including fatal or life-threatening reactions, occurred in patients receiving obecabtagene autoleucel, including concurrently with CRS or after CRS resolution.
  • Monitor for neurologic signs and symptoms after treatment with obecabtagene autoleucel. 
  • Before administering obecabtagene autoleucel, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities
  • Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity/ICANS occur. 
  • At the first sign of Neurologic Toxicity /ICANS, immediately evaluate patients for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines
• Effect on Ability to Drive and Use Machines
  • Due to the potential for neurologic events, including altered mental status or seizures, patients receiving obecabtagene autoleucel are at risk for altered or decreased consciousness or coordination in the eight weeks following obecabtagene autoleucel infusion or until resolution of the neurological event by the treating physician. 
  • Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.
• Prolonged Cytopenias
  • Patients may exhibit cytopenias including anemia, neutropenia, and thrombocytopenia for several weeks after treatment with lymphodepleting chemotherapy and obecabtagene autoleucel
  • Monitor blood counts after obecabtagene autoleucel infusion
• Infections
  • Severe, including life-threatening and fatal infections occurred in patients after obecabtagene autoleucel infusion
  • Obecabtagene autoleucel should not be administered to patients with clinically significant active systemic infections.
  • Monitor patients for signs and symptoms of infection before and after obecabtagene autoleucel infusion and treat appropriately 
  • Administer prophylactic antimicrobials according to local guidelines
  • Viral reactivation, potentially severe or life-threatening, can occur in patients treated with drugs directed against B cells
  • There is no experience with manufacturing obecabtagene autoleucel for patients with a positive test for human immunodeficiency virus (HIV) or with active hepatitis B virus (HBV) or active hepatitis C virus (HCV). 
  • Perform screening for HBV, HCV and HIV in accordance with clinical guidelines before the collection of cells for manufacturing
• Hypogammaglobulinemia
  • Hypogammaglobulinemia and B-cell aplasia can occur in patients after treatment with obecabtagene autoleucel
  • Immunoglobulin levels should be monitored after treatment with obecabtagene autoleucel and managed per institutional guidelines including infection precautions, antibiotic or antiviral prophylaxis and immunoglobulin replacement
  • The safety of immunization with live viral vaccines during or following treatment with obecabtagene autoleucel has not been studied
  • Vaccination with live viral vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy treatment, during obecabtagene autoleucel treatment, and until immune recovery following treatment
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome
  • Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions occurred after treatment with obecabtagene autoleucel. 
  • Administer treatment for HLH/MAS according to institutional standards
• Hypersensitivity Reactions
  • Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO), an excipient used in obecabtagene autoleucel
  • Observe patients for hypersensitivity reactions during and after obecabtagene autoleucel infusion
• Secondary malignancies
  • T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies
  • Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Autolus Inc at 1-855-288-5227 for reporting and to obtain instructions on the collection of patient samples for testing

Pregnancy and Lactation

• There is limited available data on obecabtagene autoleucel use in pregnant women. 
• In the FELIX study, one patient became pregnant 6 months following treatment with obecabtagene autoleucel. The patient had a premature delivery at 30 weeks of pregnancy.
• No animal reproductive and developmental toxicity studies have been conducted with
• obecabtagene autoleucel to assess whether obecabtagene autoleucelcan cause fetal harm when administered to a pregnant woman.
• It is not known if obecabtagene autoleucel has the potential to be transferred to the fetus and cause fetal toxicity
• Pregnancy testing
  • Pregnancy status of females with reproductive potential should be verified. Sexually active women of reproductive potential should have a negative pregnancy test before starting treatment with obecabtagene autoleucel.
• Contraception
  • See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy treatment.
  • There are insufficient exposure data to provide a recommendation concerning the duration of contraception following treatment with obecabtagene autoleucel.
• Infertility 
  • There are no data on the effect of obecabtagene autoleucel on fertility.
• Lactation
  • There is no information regarding the presence of obecabtagene autoleucel in human milk, its effect on breastfed infants, or milk production.
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for obecabtagene autoleucel and any potential adverse effects on the breastfed infant from obecabtagene autoleucel or the underlying maternal condition