Blincyto (blinatumomab) is an injectable immunotherapy treatment that may be used to treat B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children aged 1 month and older. It is a biologic treatment that is usually given after other cancer treatments have been tried without success.

Blincyto’s mechanism of action is to connect the protein CD3 found on the surface of T cells (a type of white blood cell that is an essential part of our immune system) to another protein, CD19 found on cancerous and non-cancerous B-cells. This activates the T-cell and Blincyto works by causing the destruction (lysis) of CD19 cells. Blincyto is a bispecific CD19-directed CD3 T-cell engager. In one study, 81% of patients with B-cell precursor ALL with minimal residual disease receiving Blincyto had no detectable cancer after 4 weeks.

Blincyto was FDA-approved on December 3, 2014. There is no generic Blincyto available.

What is Blincyto used for?

Blincyto is used to treat adults and children 1 month and older with:

• B-cell precursor ALL in remission when only a small number of cancer cells remain in the body (minimal residual disease [MRD])
• B-cell precursor ALL that has come back or did not respond to previous treatments
• Philadelphia-chromosome negative B-cell precursor ALL in the consolidation phase of chemotherapy treatment with multiple phases.

It is not known if Blincyto is safe and effective in children under 1 month of age.

Blincyto side effects

The most common side effects of Blincyto include:

• fever
• infusion-related reactions (see below)
• headache
• infections
• muscle, joint, and bone pain
• low white or red blood cell counts (neutropenia or anemia)
• low platelet count (thrombocytopenia)
• diarrhea.

Some side effects may occur during the Blincyto injection. Tell your healthcare provider right away if you feel dizzy, nauseated, light-headed, chilled or feverish, or if you have a headache, skin rash, trouble breathing, or swelling in your face.

Serious side effects and warnings

Get emergency medical help if you have signs of an allergic reaction to Blincyto such as hives; difficulty breathing; or swelling of your face, lips, tongue, or throat.

Blincyto may cause serious side effects, including:

Cytokine release syndrome (CRS) and infusion reactions. CRS can occur when your immune system responds to immunotherapy medications such as Blincyto more aggressively than it should and symptoms may be similar to infusion reactions. Tell your healthcare provider right away if you develop a fever, chills, wheezing or difficulty breathing, dizziness, headache, low blood pressure, nausea or vomiting, body aches, diarrhea, facial swelling, a skin rash, or feel tired or light-headed.

Neurologic problems. Blincyto may affect your nerves and can cause some serious neurological disorders including a potentially life-threatening neurotoxicity called immune effector cell-associated neurotoxicity syndrome (ICANS). Tell your healthcare provider right away if you experience:

• seizures
• difficulty in speaking or slurred speech
• loss of consciousness
• trouble sleeping
• confusion and disorientation
• loss of balance
• headache
• difficulty with facial movements, hearing, vision, or swallowing
• tremors.

People with Down Syndrome over the age of 10 years may have a higher risk of seizures with Blincyto.

Life-threatening infections that may lead to death. Tell your healthcare provider right away if you develop any signs or symptoms of an infection.

Tumor Lysis Syndrome (TLS) is caused by the fast breakdown of cancer cells. It can be life-threatening
and may lead to death. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with Blincyto, including:

• nausea and vomiting
• confusion
• shortness of breath
• irregular heartbeat
• dark or cloudy urine
• reduced amount of urine
• unusual tiredness
• muscle cramps.

Low white blood cell counts (neutropenia) are common with Blincyto treatment and may sometimes be life-threatening. They can increase your risk of infection. Your healthcare provider will do blood tests to check your white blood cell counts during treatment. Tell your healthcare provider right away if you get a fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands or feet, or feel light-headed or short of breath.

Abnormal liver blood tests. Your healthcare provider will do blood tests to check your liver before you start Blincyto and during treatment.

Inflammation of the pancreas (pancreatitis). Pancreatitis may happen in people treated with Blincyto and
corticosteroids. It may be severe and lead to death. Tell your healthcare provider right away if you have severe stomach-area pain that does not go away. The pain may happen with or without nausea and vomiting.

People receiving Blincyto are at risk of seizures or losing consciousness and should not drive or engage in hazardous activities.

Blincyto may harm an unborn baby and should not be taken by females who are pregnant.

Before taking this medicine

You should not use Blincyto if you are allergic to blinatumomab, Blincyto, or any inactive ingredients in the injection.

To make sure Blincyto is safe for you, tell your doctor if you have:

• nerve problems or a neurologic disorder, such as seizures, confusion, trouble speaking, or problems with balance
• Down syndrome
• a history of chemotherapy or radiation treatment to your brain
• an infection
• have recently received a vaccine or if you are scheduled for a booster dose
• are pregnant or plan to become pregnant
• are breastfeeding.

Pregnancy

Blincyto may harm an unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Blincyto. Females who are able to become pregnant should use an effective form of birth control (contraception) during treatment with Blincyto, and for 48 hours after their last dose. Do not use Blincyto if you are pregnant. If you inadvertently become pregnant while receiving Blincyto, tell your healthcare provider right away.

Breastfeeding

It is not known if Blincyto passes into your breast milk. You should not breastfeed while using this medicine and for at least 48 hours after your last dose.

How is Blincyto administered?

Blincyto will be given to you by a continuous intravenous (IV) infusion into your vein using a small portable infusion pump. This means you can still carry out daily activities as normal, although you should be careful not to drive or engage in hazardous tasks while receiving the infusion.

• One induction treatment cycle is usually 4 weeks (28 days) of continuous infusion followed by 2 weeks (14 days) break without infusion.
• For the first 3 to 9 days of the first cycle and the first 2 days of the second cycle, you will usually receive this in a hospital under the care of your healthcare provider.
• For the rest of the cycle, your healthcare provider will decide if you receive your treatment at home or through an outpatient clinic or infusion center.
• Your healthcare provider will decide the number of treatment cycles of Blincyto but a treatment course for MRD is usually 1 cycle of Blincyto for induction followed by up to 3 additional cycles for consolidation (continued therapy). This usually consists of one IV infusion for 4 weeks (28 days), followed by an 8-week (56 days) break during which you will not receive Blincyto. This is 1 consolidation treatment cycle (84 days).
• Your healthcare provider may change your dose of Blincyto, delay, or completely stop treatment if you have certain side effects, and do blood tests during treatment to check you for side effects.

Before receiving Blincyto, you will be given a corticosteroid medicine to help reduce infusion reactions.

Before and during treatment, you may be given chemotherapy as an injection into the space that
surrounds the spinal cord and the brain (intrathecal injection) to help prevent central nervous system relapse of ALL.

• It is very important to keep the area around the IV catheter clean to reduce the risk of getting an infection. Your healthcare provider will show you how to care for your catheter site.

Receiving Blincyto at home

If your healthcare provider has decided you can receive Blincyto at home, your infusion bag will be changed at an outpatient center or by your home healthcare provider.

• Blincyto is available in 24-hour, 48-hour, and 7-day infusion bags. Your bag will need to be changed every day, every 2 days, or once a week based on what your doctor decides is best for you.
• Call your doctor if you experience any problems or side effects.
• Do not change the settings on your infusion pump, even if there is a problem with your pump or your pump alarm sounds. Any changes to your infusion pump settings may cause a dose that is too high or too low to be given.
• Call your healthcare provider or nurse right away if you have any problems with your pump or your pump alarm sounds.
• Keep Blincyto out of reach of children or pets in the household.

What happens if I miss a dose?

Call your healthcare provider if you do not receive your IV bags on time or if your home healthcare provider does not change the infusion bag in time.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line .

Overdose symptoms may include fever, tremors, and headache.

What should I avoid while using Blincyto?

Do not receive a “live” vaccine while using Blincyto, or you could develop a serious infection. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), and zoster (shingles). Ask your doctor how soon it is safe for you to receive a vaccine after you stop using this medicine.

Avoid driving or hazardous activity until you know how Blincyto will affect you. Blincyto increases your risk of seizures, losing consciousness, and a serious nerve toxicity syndrome called ICANS (see above).

What other drugs will affect Blincyto?

Other drugs may interact with blinatumomab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

No formal drug interaction studies have been conducted with Blincyto. The highest drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the second cycle. People receiving medications with a narrow therapeutic index metabolized by the cytochrome p450 system, such as warfarin or cyclosporin should be monitored for increases in side effects and the dosage of the interacting drug adjusted if needed.

No formal drug interaction studies have been conducted with Blincyto, but starting Blincyto treatment causes the short-lived release of cytokines that may suppress CYP450 enzymes and affect medications with a narrow therapeutic index, such as warfarin.

Storage

Intravenous (IV) bags containing Blincyto for infusion will arrive in a special package.

• Do not open the package.
• Do not freeze the package.

The package containing Blincyto will be opened by your healthcare provider and stored in the refrigerator at 36°F to 46°F (2°C to 8°C).

The prepared preservative-free Blincyto infusion bag lasts for 48 hours at room temperature 73°F to 81°F (23°C to 27°C) or 8 days when refrigerated at 36°F to 46°F (2°C to 8°C).

The prepared preservative-containing Blincyto infusion bag lasts for 7 days at room temperature 73°F to 81°F (23°C to 27°C) or 14 days when refrigerated at 36°F to 46°F (2°C to 8°C).

Do not throw away (dispose of) any Blincyto in your household trash. Talk with your healthcare provider about the disposal of Blincyto and used supplies.

Keep out of reach of children.

Blincyto infusion ingredients

Active ingredient: blinatumomab.
Inactive ingredients: citric acid monohydrate, lysine hydrochloride, polysorbate 80, trehalose dihydrate, sodium hydroxide, and preservative-free sterile water for injection.
Inactive ingredients of IV solution stabilizer: citric acid monohydrate, lysine hydrochloride, polysorbate 80, sodium hydroxide, and water for injection.

Due to the addition of bacteriostatic saline, 7-day bags of Blincyto solution for infusion with a preservative contain benzyl alcohol and are not recommended for use in patients weighing less than 22 kg.

Available as Blincyto 35 mcg in a single-dose vial for reconstitution.

Who makes Blincyto?

Amgen Inc. makes Blincyto 35 mcg single-dose vials for reconstitution.

Blincyto Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Blincyto.Blincyto (blinatumomab) – Amgen Inc.

What is Imdelltra?

Imdelltra (tarlatamab) is an immunotherapy treatment that may be used to treat adults with extensive-stage small cell lung cancer (ES-SCLC) which has progressed after receiving platinum-based chemotherapy.

• ES-SCLC is when small cell lung cancer has spread throughout the lung or to other parts of the body.
• Imdelltra is given by intravenous infusion (infusion into a vein) by a healthcare provider.

Imdelltra (full biologic name tarlatamab-dlle) is a bispecific T-cell engager with two arms that activate a patient’s T-cells to attack Delta-like ligand (DLL3)-expressing SLCL. One part of Imdelltra works by binding to DLL3 expressed on the surface of cells, including tumor cells, and the other part binds to CD3 expressed on the surface of T-cells. This brings T-cells and tumor cells closer, activating the immune system directly at the cancer site.

Imdelltra was FDA-approved on 16 May 2024 under the accelerated approval designation. Continued approval may be contingent upon continued benefits seen in clinical trials.

How effective is Imdelltra?

Imdelltra is significantly more effective than historical treatments for EC-SCLC. Even though SCLC is rare (2% to 5% of lung cancer cases), it’s aggressive, there are few treatment options, and survival is poor.

Results from the phase 2 DeLLphi-301 trial by Amgen reported that Imdelltra 10 mg infusion given every 2 weeks reduced tumors in 40% of ES-SCLC patients with a median overall survival of 14.3 months (previous survival duration with no treatment/other treatments is approximately 5 months).

Imdelltra side effects

The most common side effects of Imdelltra affecting 20% or more people include:

• Cytokine release syndrome
• Fatigue and tiredness
• Fever
• A bad or metallic taste in your mouth
• Decreased appetite
• Muscle and bone pain
• Constipation
• Nausea.

The most common severe abnormal lab test results with Imdelltra include decreased white blood cells, decreased sodium, increased uric acid, decreased red blood cells, increased blood clotting time, decreased potassium, increased liver enzymes, and decreased platelets.

Serious side effects and warnings

Imdelltra comes with a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).

Cytokine Release Syndrome (CRS). CRS is a condition that happens when your immune system responds to infection and immunotherapy drugs more aggressively than it should. It is common during Imdelltra treatment and can be serious and life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS, including:

• Fever of 100.4°F (38°C) or higher
• Low blood pressure
• Tiredness
• Fast heartbeat or dizziness
• Headache
• Shortness of breath or trouble breathing
• Nausea and vomiting
• Confusion, restlessness, or feeling anxious
• Problems with balance and movement, such as trouble walking
• Heart, liver, or kidney problems
• Unusual bleeding or bleeding that lasts a long time.

Low blood cell counts (cytopenias). Decreased blood cell counts are common with Imdelltra and can also be severe and may include:

• Low white blood cell counts (neutropenia) which can increase your risk for infection.
• Low red blood cell counts (anemia) which can cause tiredness and shortness of breath.
• Low platelet counts (thrombocytopenia) which can cause bruising or bleeding problems.

Infections. Imdelltra can cause serious infections that can be life-threatening and may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any signs or symptoms of infection, such as:

• Fever of 100.4°F (38°C) or higher
• Painful rash
• Cough
• Sore throat
• Chest pain
• Pain during urination
• Tiredness
• Feeling weak or generally unwell
• Shortness of breath.

Liver problems. Imdelltra can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any signs or symptoms of liver problems, including:

• Tiredness
• Loss of appetite
• Pain in your right upper stomach area (abdomen)
• Dark urine
• Yellowing of your skin or the white part of your eyes.

Allergic reactions. Imdelltra can cause allergic reactions that can be severe. Go to the nearest emergency room or get medical help right away if you develop any signs or symptoms of a severe allergic reaction during treatment such as:

• Shortness of breath or trouble breathing
• Pain or tightness in your chest and back
• Wheezing
• Coughing
• Feeling lightheaded or dizzy
• Rash.

Neurologic problems, that can be serious or life-threatening. These may happen days or weeks after you receive Imdelltra. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:

• Trouble speaking, memory loss, or personality changes
• Confusion, feeling disoriented, slow thinking, or not being able to think clearly
• Seizures
• Problems with walking, loss of balance, or coordination
• Weakness or numbness of your arms or legs
• Shaking (tremors)
• Headache
• Numbness or tingling of your hands or feet
• Trouble sleeping
• Fainting or loss of consciousness
• Feeling like you have no energy.

May cause harm to an unborn baby.

It is not known if Imdelltra is safe and effective in children.

These are not all of the possible side effects of Imdelltra. Call your doctor for medical advice about side effects. You may report side effects to the FDA

Before taking

Before receiving Imdelltra, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection or signs of an infection
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Your healthcare provider will do bloodwork before you start and during treatment with Imdelltra and monitor you for signs or symptoms of these serious side effects during treatment and may temporarily or completely stop treatment if you develop certain serious side effects.

Pregnancy

Imdelltra may harm your unborn baby. For females who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Imdelltra and you should use an effective form of birth control (contraception) during treatment, and for 2 months after your last dose.

Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment.

Breastfeeding

It is not known if Imdelltra passes into your breast milk. Do not breastfeed during treatment with Imdelltra and for 2 months after the last dose.

How is Imdelltra administered?

Imdelltra is administered by a healthcare provider in a clinic or hospital.

• It is administered by intravenous (IV) infusion through a needle placed in a vein.
• The infusion will take about 1 hour.

Your Imdelltra treatment schedule is divided into cycles that are usually 28 days (4 weeks) long.

• Your healthcare provider will decide how many treatment cycles you will receive.
• Due to the risk of CRS, you will receive Imdelltra on a “step-up dosing schedule”:
• This means you will receive a smaller dose of Imdelltra on Day 1 of your first treatment cycle (Cycle 1).
• You will receive the full treatment dose on Day 8 and Day 15 of Cycle 1.
• You will receive the full treatment dose 1 time every 2 weeks after Day 15 of Cycle 1.
• If your dose of Imdelltra is delayed for any reason, you may need to repeat the “step-up dosing schedule”.

Before receiving your Day 1 and Day 8 doses of Cycle 1, you will be given a medicine to help reduce your risk of CRS. This will be given into your vein by intravenous (IV) infusion.

• You will also receive IV fluids after each of your Cycle 1 doses of Imdelltra (on Day 1, Day 8, and Day 15). Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.

Due to the risk of CRS and neurologic problems, you will receive the following monitoring during treatment

• For Day 1 and Day 8 of Cycle 1 doses, your healthcare provider will monitor you for 22 to 24 hours from the start of the Imdelltra infusion in an appropriate healthcare setting that can manage these side effects.
  • You should stay within 1 hour of an appropriate healthcare setting for a total of 48 hours from the start of the Imdelltra infusion after your Day 1 and Day 8 of Cycle 1 doses and be accompanied by a caregiver.
• For Day 15 of Cycle 1 and Cycle 2 doses, your healthcare provider will watch you for 6 to 8 hours after the Imdelltra infusion.
• For Cycle 3 and Cycle 4 doses, your healthcare provider will watch you for 3 to 4 hours after the Imdelltra infusion.
• For Cycle 5 and later doses, your healthcare provider will watch you for 2 hours after the Imdelltra infusion.

Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with Imdelltra, as well as other side effects, and treat you as needed. You may be hospitalized if you develop signs or symptoms of CRS or neurologic problems during treatment.

• Your healthcare provider may temporarily stop or completely stop your treatment with Imdelltra if you develop CRS, neurologic problems, or any other severe side effects.

What should I avoid while receiving Imdelltra?

Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities, including work-related activities, during treatment with Imdelltra if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

What other drugs will affect Imdelltra?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Specific drug interactions are not listed in the product information for Imdelltra but other medications that have similar side effects, for example, cause CRS, low blood cell counts, liver problems, affect the immune system, or cause neurological problems, may potentially interact.

Talk to your healthcare provider about interactions with Imdelltra or refer to the Imdelltra Package Insert.

Storage

Your healthcare provider will store Imdelltra and the IV Solution Stabilizer (IVSS) vials in the refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect it from light until the time of use. Do not freeze.

May be kept at room temperature between 20°C to 25°C (68°F to 77°F) for up to 24 hours in the original carton to protect it from light.

Imdelltra ingredients

Active ingredients: tarlatamab-dlle

Inactive ingredients: glutamic acid, polysorbate 80, sucrose, and sodium hydroxide.

Inactive ingredients of IV solution stabilizer: citric acid monohydrate, lysine hydrochloride, polysorbate 80, sodium hydroxide, and water for Injection.

Available in 1mg and 10mg vials that require reconstitution and further dilution.

Who makes Imdelltra?

Amgen Inc., makes Imdelltra

Imdelltra Biosimilars

Biosimilar and interchangeable products are biological products that are highly similar to and have no clinically meaningful differences from the reference product.

Reference products

These are biological products that have already been approved by the FDA, against which biosimilar products are compared. There is 1 for Imdelltra.Imdelltra (tarlatamab-dlle) – Amgen Inc.