Ciltacabtagene Autoleucel - Treatment for Multiple Myeloma

Overview

Approved by the Food and Drug Administration (FDA), Ciltacabtagene autoleucel is a drug that is used in immunotherapy to treat the cancer of plasma cells. The cancer of the plasma cells leads to multiple myeloma. It is a relatively uncommon type of cancer and cannot be permanently cured. Ciltacabtagene autoleucel shows the best results in cases of relapsed and refractory multiple myeloma, wherein patients have received four to five various therapies, all of which have failed to produce results.

How Does Ciltacabtagene Autoleucel Work?

Ciltacabtagene autoleucel, a B-cell maturation antigen, also known as BMCA, is primarily a genetically modified autologous chimeric antigen receptor (CAR) T - cell therapy. In essence, each dose is made by tailor-made customizations, using the patient’s own T-cells, which are genetically modified following collection and are then infused back into the patient. Following the infusion, Ciltacabtagene autoleucel binds to the BMCA, which is universally found on all myeloma cells, or cancerous plasma cells, and eventually eliminates them.

Uses of Ciltacabtagene Autoleucel:

Ciltacabtagene autoleucel is indicated in the following conditions -

• Refractory multiple myeloma, following four to five failed previous therapies.

• Relapsed multiple myeloma, wherein the patient has received four to five lines of different therapies in the past.

Available Forms and Administration of Ciltacabtagene Autoleucel:

Ciltacabtagene autoleucel is freshly prepared and available in the form of a suspension, which is administered through an intravenous drip line.

Warnings and Precautions:

1. To ensure the traceability of the suspension, the batch number of the treated patient and the batch of the infusion should be kept for a time frame of 30 years, following the expiry of the drug.

2. Ciltacabtagene autoleucel is only for autologous use, meaning that each suspension should be used only once, and for the same patient from whom the cells were extracted before making the preparation. It cannot be used for another patient, even if they belong to the same family.

3. The drug can cause drowsiness, fatigue, mental confusion and general malaise. Hence patients should refrain from operating machinery and driving vehicles for at least eight weeks following the infusion.

4. Following the infusion, patients should not donate organs, blood, cells, and tissues for transplantation.

5. Ciltacabtagene autoleucel is associated with cytokine release syndrome, which can be highly fatal and life-threatening if not monitored appropriately. Hence patients should be monitored carefully following the infusion. The signs and symptoms associated with cytokine release syndrome are -

• Fever.

• Rigors and chills.

• Low blood pressure.

• Elevated liver enzymes.

• Decreased oxygen saturation.

Use in Specific Population:

• Geriatric Population: Studies reveal that dose modifications are not required if the patients are 65 years or more.

• Pediatric Population: No significant data is available about the consequences of the drug on the pediatric population. Hence, a thorough assessment should be made before administering the drug to this population.

• Nursing and Breastfeeding Population: No significant data is available about the consequences of the drug when administered to nursing or breastfeeding mothers. Since several drugs are excreted through human milk, a thorough assessment should be made before administering the drug to this population.

• Pregnant Women: No significant data is available about the consequences of the drug when administered to pregnant women. Since several drugs when consumed during pregnancy can harm the developing fetus, a thorough assessment should be made before administering the drug to this population.

For Patients

What Is Multiple Myeloma?

Multiple myeloma is a malignant disease of the plasma cells in the bone marrow. It is the second most common type of hematological or blood-borne cancer and generally affects older individuals. Multiple myeloma lacks a hereditary genetic component and definitive environmental risk factors. The different types of blood cells are formed by the healthy stem cells which are produced in the bone marrow. These blood cells usually help carry oxygen and allow blood to clot, which in turn helps in the cessation of bleeding. These cells also help fight various infections. When plasma cells get affected, they become cancerous and are then referred to as myeloma cells. These myeloma cells tend to multiply and collect within the bone marrow. These cells are also known to produce various proteins, such as the paraprotein, which can lead to organ damage. Furthermore, the accumulation of myeloma cells in the bone prevents and impedes the formation of healthy red blood cells. This can also result in the weakening of the bone and various kinds of bone pain. Multiple myeloma can often be treated, although it will not be permanently cured.

What Are the Common Signs and Symptoms Associated With Multiple Myeloma?

Some of the most common signs and symptoms associated with multiple myeloma include the following -

• Back pain.

• Infections of the respiratory tract.

• Anemia.

• Tiredness and fatigue.

• Renal failure.

• Increased excretion of proteins in the urine, otherwise known as proteinuria.

• Bone pain.

• Dehydration.

• Bone fractures.

• Kidney disorders.

How Is Multiple Myeloma Diagnosed?

Multiple myeloma can be diagnosed by employing the following tests -

• Blood Tests - A complete blood count helps analyze the levels of all blood cells, allowing the physicians to detect the presence of anemia.

• Blood Chemistry Tests - These tests are performed to analyze the levels of blood albumin, creatinine, calcium, and electrolytes. These tests help assess kidney function and also identify the possibility of fractures due to weakened bones.

• Urine Test - This is performed to assess the levels of the myeloma protein in the urine.

• Electrophoresis - This is performed to assess the various proteins and antibodies that are typical of multiple myeloma.

What Is Ciltacabtagene Autoleucel and How Does It Work?

Ciltacabtagene autoleucel is an FDA-approved drug that is used to treat multiple myeloma in adults, specifically in cases of refractory or relapse. Ciltacabtagene autoleucel is essentially immunotherapy, a B-cell maturation antigen, also known as BMCA, which is primarily a genetically modified autologous chimeric antigen receptor (CAR) T - cell therapy. Simply put, each dose is made by tailored-made customizations, using the patient’s own T-cells, which are genetically modified following collection, and are then infused back into the patient. Following the infusion, Ciltacabtagene autoleucel binds to the BMCA, which is universally found on all myeloma cells, or cancerous plasma cells, and eventually eliminates them.

What Are the Uses of Ciltacabtagene Autoleucel?

Ciltacabtagene autoleucel is an FDA-approved drug that is used to treat multiple myeloma in adults, specifically in the following scenarios -

• Relapse of multiple myeloma, wherein the patient has received four to five lines of different therapies in the past.

• Refractory multiple myeloma, wherein, the patient has received four to five lines of various therapies in the past.

What Is the Dosage of Ciltacabtagene Autoleucel?

The dosage varies in the following manner -

• The Target Ideal Dose - 0.75 x 106 CAR-positive viable T cells/kg of body weight (not exceeding 1.0 × 108CAR-positive viable T cells).

• For Patients, Weighing 100 KG and Below, the Dose Is - 0.5 - 1.0 x 106CAR-positive viable T cells/kg body weight.

• For Patients Weighing Above 100 KG, the Dose Is - 0.5 - 1.0 x 108 CAR-positive viable T cells (non-weight based).

• Missed Dose: In the event of missing a dose, patients should reach out to their healthcare professional to schedule the consequent dose of Ciltacabtagene autoleucel soon.

How Should Ciltacabtagene Autoleucel Be Used?

• Ciltacabtagene autoleucel should be given only by healthcare professionals and should never be self-administered.

• It comes in the form of suspension, which is primarily made of patients' modified white blood cells. The cells are first withdrawn, the modifications are made and then the cells are infused back into the patient, through a drip line in the veins, over an hour or two.

• However, before administering Ciltacabtagene autoleucel the patient receives a short course of chemotherapy which aims at reducing the white blood cell count.

• Apart from chemotherapy, right before the infusion, healthcare providers inject paracetamol and anti-histamines, which aim at reducing the risk of reactions associated with the infusion drip.

• Following the infusion, the patients are kept under observation, in a hospital set-up, for two weeks and then periodically for a fortnight.

What Special Dietary Instructions Should Be Followed?

Unless informed otherwise, patients do not need to make any dietary modifications and can continue following their regular diet.

What Are the Side Effects of Ciltacabtagene Autoleucel?

As with any medication, the use of Ciltacabtagene autoleucel is also associated with side effects. They include -

• Diarrhea.

• Loss of appetite.

• Joint pain.

• Muscle pain.

• Bone pain.

• Swelling at the injection site.

• Constipation.

• Fever.

• Rigors and chills.

• Low blood pressure.

• Elevated liver enzymes.

• Decreased oxygen saturation.

In case any of the following side effects are elicited, patients should be rushed to the hospital -

• Swelling of the face.

• Shortness of breath.

• Skin rash.

• Itchy skin.

• Hives.

• Swelling of the lips, mouth, and tongue.

• Chest pain.

• Difficulty in swallowing.

• A block-like sensation in the throat.

• Fast and rapid heartbeat.

• Chest palpitations.

How Is Ciltacabtagene Autoleucel Stored and Discarded?

• Ciltacabtagene autoleucel should be stored and transported in the vapor phase of liquid nitrogen, wherein the temperature is maintained at least -120 degrees Celsius.

• It should be kept frozen until the patient is completely prepared and ready for infusion.

• Once thawed, Ciltacabtagene autoleucel should not be shaken, refrigerated, or re-frozen.

• The infusion bag should be always placed in an aluminum cryo cassette.

• One Ciltacabtagene autoleucel is thawed, it can be stored at room temperature, between 20 degrees Celsius and 25 degrees Celsius, for a maximum of two and a half hours. After thawing, the infusion should be administered immediately and should pan over two hours.

• In general, unless thawed, Ciltacabtagene autoleucel has a shelf life of nine months.

• Ciltacabtagene autoleucel should be discarded under local guidelines and medical regulatory bodies. It should not be irradiated as its irradiation could inactivate the drug.

What Steps Are Taken for Preparing the Infusion of Ciltacabtagene Autoleucel?

Several steps are taken before administering the infusion of Ciltacabtagene autoleucel, such as-

• The timings of thawing and administration of the infusion should be coordinated with a maximum interval of two and a half hours between both.

• Before making the preparation, the identity of the patient should be identified by the identifiers on the cryo cassette.

• The Ciltacabtagene autoleucel’s infusion bag should not be removed from the cassette if the patient details do not match.

• Ciltacabtagene autoleucel’s infusion bag should be checked thoroughly for any damage and breaches. In the case of damage, the infusion bag should not be used.

• For thawing, Ciltacabtagene autoleucel’s infusion bag should be placed in a sealed plastic bag and thawed between 35 degrees Celsius and 37 degrees Celsius, either using a dry thaw device or a water bath.

• Thawing is done until there is no visible ice in Ciltacabtagene autoleucel’s infusion.

• The total time required for thawing should never exceed fifteen minutes.

• Once thawed efficiently, the pouch should be taken out from the sealed plastic bag and wiped dry.

• The contents of the pouch should be gently mixed, allowing the dispersion of clumps of cellular material.

• Once ready, the entire contents of the bag should be infused in a single shot, over an intravenous drip, panning two and a half hours.

• Once the infusion is over, the intravenous drip line should be flushed with 0.9 percent sodium chloride. This ensures that all the contents of the pouch are delivered efficiently.

What Should Be Done in the Case of Overdose?

Studies do not provide data on the consequences of overdose. However, in the event of any signs and symptoms, patients should rush to the hospital for further investigation.

In Which Conditions Should Ciltacabtagene Autoleucel Not Be Used?

Ciltacabtagene autoleucel should not be used in the following groups -

• Patients having an allergy to Cryostor CS5 (which contains Dimethyl Sulfoxide).

• Children.

• Pregnant women.

• Patients having a history of recent infection.

• Patients with a history of renal disease.

• Patients with a history of hepatic disease.

• Patients with a recent history of cardiac dysfunction.

What Should Be Informed to the Healthcare Provider Before Using Ciltacabtagene Autoleucel?

Before starting the therapy, patients should inform the following to their healthcare provider -

• Patients should inform of any prior and present allergies to Ciltacabtagene autoleucel, its constituents, and Dimethyl Sulfoxide.

• Patients should also disclose their history of all kinds of allergies.

• Patients should inform their healthcare providers about any drugs, medications, vitamins, and non-prescription pills that they might be consuming.

• Patients planning on pregnancy or breastfeeding should discuss various options before starting the therapy.

• Patients should also disclose any prior history of the diseases and conditions such as cytomegalovirus, hepatitis B and hepatitis C, human immunodeficiency virus (HIV), kidney diseases, heart diseases, and liver diseases.

For Doctor

Indications of Ciltacabtagene Autoleucel:

Ciltacabtagene autoleucel is indicated in the following conditions -

• Refractory multiple myeloma, following four to five failed previous therapies.

• Relapsed multiple myeloma, wherein the patient has received four to five lines of different therapies in the past.

Contraindications of Ciltacabtagene Autoleucel:

Ciltacabtagene autoleucel is contraindicated in the following conditions and groups -

• Allergies to Cryostor CS5 (which contains Dimethyl Sulfoxide).

• Pediatric population.

• Pregnant and lactating women.

• Recent history of infection.

• Renal disease.

• Hepatic disease.

• Cardiac dysfunction and disorders.

Available Forms and Administration of Ciltacabtagene Autoleucel:

Ciltacabtagene autoleucel is freshly prepared and available in the form of a suspension, which is administered through an intravenous drip line.

Pharmacology of Ciltacabtagene Autoleucel -

Mechanism of Action of Ciltacabtagene Autoleucel:

The autologous T-cells are genetically modified using a CAR (chimeric antigen receptor) T-cell therapy, known as Ciltacabtagene autoleucel, which reprograms them to target B-cell maturation antigen (BMCA), a biomarker of multiple myeloma. Following this, these genetically modified CAR T-cells then expand, get washed, and cryopreserved for being infused back into the patient. This results in easier identification of the BCMA-expressing target cells, including the malignant plasma cells involved in multiple myeloma.

Half-Life of Ciltacabtagene Autoleucel:

Following a single infusion of a median dose of 0.71 x 106 CAR-positive viable T cells/kg Ciltacabtagene autoleucel, the median half-life was calculated as 15.3 days.

Adverse Effects of Ciltacabtagene Autoleucel:

The adverse effects of Ciltacabtagene autoleucel include the following-

• Diarrhea.

• Loss of appetite.

• Arthralgia.

• Myalgia.

• Bone pain.

• Swelling at the injection site.

• Constipation.

• Swelling of the face.

• Shortness of breath.

• Skin rash.

• Pruritis.

• Hives.

• Swelling of the lips, mouth, and tongue.

• Chest pain.

• Difficulty in swallowing.

• A block-like sensation in the throat.

• Fast and rapid heartbeat.

• Chest palpitations.

• Fever.

• Rigors and chills.

• Hypotension.

• Elevated liver enzymes.

• Hypoxia.

• Cardiac dysfunction.

• Neurologic toxicity.

• Bleeding.