Understanding ABECMA (idecabtagene vicleucel)

Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest organization focusing specifically on myeloma. The IMF’s reach extends to more than 525,000 members in 140 countries. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure through our four founding principles: Research, Education, Support, and Advocacy.

RESEARCH

The IMF is dedicated to finding a cure for myeloma, and we have a range of initiatives to make this happen. The International Myeloma Working Group, which emerged from the IMF’s Scientific Advisory Board established in 1995, is the most prestigious organization with more than 200 myeloma researchers conducting collaborative research to improve outcomes for patients while providing critically appraised consensus guidelines that are followed around the world. Our Black Swan Research Initiative® is bridging the gap from long-term remission to cure. Our annual Brian D. Novis Research Grant Program is supporting the most promising projects by junior and senior investigators. Our Nurse Leadership Board, comprised of nurses from leading myeloma treatment centers, develops recommendations for the nursing care of myeloma patients.

EDUCATION

The IMF’s webinars, seminars, and workshops provide up-to-date information presented by leading myeloma scientists and clinicians directly to patients and their families. We have a library of more than 100 publications for patients, care partners, and healthcare professionals. IMF publications are always free-of-charge, and available in English and select other languages.

SUPPORT

The IMF InfoLine responds to your myeloma-related questions and concerns via phone and email, providing the most accurate information in a caring and compassionate manner. We also sustain a network of myeloma support groups, training hundreds of dedicated patients, care partners, and nurses who volunteer to lead these groups in their communities.

ADVOCACY

We empower thousands of individuals who make a positive impact each year on issues critical to the myeloma community. In the US, we lead coalitions to represent the interests of the myeloma community at both federal and state levels. Outside the U.S., the IMF’s Global Myeloma Action Network works to help patients gain access to treatment.

Learn more about the ways the IMF is helping to improve the quality of life of myeloma patients while working toward prevention and a cure. Call us at 1.818.487.7455 or 1.800.452.CURE, or visit myeloma.org .

Table of contents

You are not alone 4

What you will learn from this booklet 4

Immunotherapy 4

CAR T-cell therapy 5

Who is a candidate for Abecma 5

Clinical trial experience with Abecma 5

How Abecma works 6

Effects on ability to drive and operate machinery 8

Important safety information 8

Possible common side effects of Abecma 8 Access to Abecma 9

In closing 9 Terms and definitions 10

You are not alone

The International Myeloma Foundation is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family. We achieve this through a broad range of resources available on our website myeloma.org, the IMF InfoLine, seminars, webinars, workshops, and other programs and services.

Myeloma is a cancer that is not known to most patients at the time of diagnosis. It is important and helpful to learn as much as possible about myeloma and its treatment options in order to play an active role in your own medical care and to make good decisions about your care with your doctor. The information in this booklet will help you in discussions with your healthcare team.

What you will learn from this booklet

Understanding ABECMA® (idecabtagene vicleucel) focuses on the first-in-class B-cell maturation antigen (BCMA) -directed chimeric antigen receptor (CAR) T-cell immunotherapy approved by the U.S. Food and Drug Administration (FDA) for use in myeloma. Abecma (also known as "ide-cel") is the first CAR T-cell therapy to be approved by the FDA for patients with myeloma, and it is the first CAR T-cell therapy approved by the FDA that targets BCMA.

Words in bold+blue type are explained in the “Terms and definitions” section at the end of this booklet. The IMFs’ Glossary of Myeloma Terms and Definitions, a more complete myeloma-related compilation, is located at glossary.myeloma.org.

If you are reading this booklet in electronic format, the light blue hyperlinks will take you to the corresponding resources. All IMF publications are free-of-charge and can be downloaded or requested in printed form at publications.myeloma.org.

If you are newly diagnosed with myeloma, we suggest that you read the IMF’s publication Patient Handbook for the Newly Diagnosed, which will help you to better understand this complex disease.

Immunotherapy

Myeloma interferes with the normal function of the body’s immune system. Immunotherapy, which is sometimes called “biological therapy,” is treatment that enhances the body’s natural defenses. Designed to protect us from harm, the immune system is very complex.

T cells (T lymphocytes) are one of the most important parts of our immune system. T cells recognize myeloma cells as foreign and cancerous. However, as myeloma grows, the number of these key T cells is significantly reduced

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and their function blocked, thus allowing the myeloma to continue to grow. What is needed are T cells which recognize myeloma cells as foreign and are capable of destroying them.

CAR T-cell therapy

CAR T-cell therapy with Abecma takes the patient’s own T cells and engineers them to attack and destroy the myeloma. The T cells are engineered to identify the BCMA antigen or receptor found on the surface of myeloma cells, bind to this antigen, and destroy the myeloma cells. (BCMA is found on healthy cells as well.)

To achieve this goal, the T cells are “harvested” from the bloodstream and then sent to a highly specialized manufacturing laboratory to be engineered to attack the myeloma. This process, which involves both the engineering and the growing of enough active T cells for the therapy to be effective, takes approximately 4 weeks. Then the Abecma BCMA T-cell product is administered to the patient by way of an infusion. The infused T cells immediately begin attacking the myeloma.

Who is a candidate for Abecma

In March 2021, the FDA approved Abecma for the treatment of adult patients with relapsed or refractory myeloma after four or more prior lines of therapy including an immunomodulatory agent , a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

In May 2021, Abecma was approved in Canada for adult patients with myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody and who are refractory to their last line of treatment.

In August 2021, the European Commission approved Abecma for patients with relapsed and refractory myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression while still receiving their last treatment regimen. It was granted conditional approval for one year, which can be converted to full marketing authorization once additional data is submitted and assessed.

Clinical trial experience with Abecma

The FDA approval of Abecma was based on the results of the phase II KarMMa clinical trial. Patients were treated with their own T cells, which were engineered to target BCMA. In this study, 128 patients received treatment. Rapid, deep, and durable responses were achieved by 72% of patients. Minimal residual disease (MRD)-negative status was achieved

in 33 (26%) of treated patients. The safety profile of Abecma is generally predictable, including cytokine release syndrome (CRS) and neurologic toxicities that are mostly low-grade with early onset and resolution. The CRS toxicity is a result of the active destruction of the myeloma cells by the BCMA-targeted T cells.

Dr. Nikhil C. Munshi, the principal investigator of the KarMMa clinical trial, summarizes the importance of Abecma as follows: “In the phase II KarMMa clinical trial, ide-cel elicited rapid responses in the majority of patients, and these deep and durable responses were observed in patients with triple-class exposed and refractory multiple myeloma. As a treating physician, I often work with patients with relapsed or refractory myeloma who are in critical need of new therapies. Now, with the FDA approval of Abecma, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion.”

The results of the KarMMa clinical trial were extremely promising, with a median response duration of 10.9 months, median progression-free survival (PFS) of 8.6 months, and median overall survival (OS) of 24.8 months. Patients who achieved a complete response (CR) or better had a longer response duration of 19 months. The patients participating in the study had a one-time infusion of CAR T cells and had no treatment after the infusion was done, therefore allowing for a longer time off myeloma therapy. The response rates demonstrated in the phase II KarMMa clinical trial of Abecma in relapsed and refractory myeloma offer an opportunity for patients with heavily pretreated disease to have deep and durable responses. Furthermore, a one-time infusion approach allows patients more time without ongoing therapy.

Numerous additional clinical trials with Abecma are ongoing or planned.

How Abecma works

Abecma is a personalized immune cell therapy delivered as a one-time infusion, manufactured for each individual patient using the patient’s own T cells. In brief, the process of CAR T-cell therapy is about collecting a patient’s T cells, training them to attack myeloma cells, multiplying those T cells in the lab, and then finally giving them back to the patient.

Collection

Much like collecting stem cells for an autologous transplant, the patient’s own T cells are collected by a procedure called apheresis or leukapheresis.

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Manufacturing

The manufacturing process inserts into the collected T cells a gene that makes the cells express a chimeric antigen receptor (CAR) on the cell surface. CARs are "hooks” added to your T cells to create ABECMA that is unique to you. This is how the patient’s harvested T cells are genetically modified to recognize and attach to BCMA, a protein that is nearly universally expressed on myeloma cells. The patient’s T cells are multiplied in the lab to manufacture millions of cells. This usually takes approximately 4 weeks.

Preparation

Approximately 5 days before the CAR T cells are reinfused, the patient begins a 3-day, low-dose chemotherapy regimen in order to prepare the body to more easily receive the CAR T cells.

Infusion

Due to the specialized nature of T-cell therapy, Abecma must be administered at a certified treatment center. Approximately 4 weeks after the initial T-cell collection, the CAR T cells are infused into the patient through an intravenous (IV) catheter. The Abecma dose can be administered in one or more infusion bags, with up to 30 minutes for each infusion bag. The CAR T cells will now seek out the myeloma cells in the body and attach to them. As a precaution, in case possible side effects occur during this process, most patients are admitted to the hospital for about a week.

Activation

Abecma recognizes and binds to BCMA on myeloma cells, leading to the destruction of BCMA-expressing myeloma cells. The CAR T cells become activated and begin to directly destroy the cell and also to engage other parts of the immune system to help.

Monitoring

For at least 7 days after the infusion, the patient is monitored daily at the certified healthcare facility where treatment was administered. For the doctor to check that the Abecma treatment is working and to help with any potential side effects, patients should remain within 2 hours of the certified healthcare facility where treatment was administered for at least 4 weeks after being treated with Abecma. This is the approximate timeline of treatment with Abecma, but every patient is different and the total time it takes to complete the process may vary.

Effects on ability to drive and operate machinery

For at least 8 weeks following the Abecma infusion, you may be at risk for temporary memory and coordination problems, sleepiness, confusion, dizziness, and seizures. Don’t drive, operate heavy machinery, or engage in any activities that could be dangerous or hazardous if you are not mentally alert. Be sure to discuss with your healthcare team any potential issues that you may be experiencing.

Important safety information

Abecma may cause side effects that are severe or life-threatening. Immediately contact your doctor or get emergency help if you experience any of the following: ¡ difficulty breathing, ¡ fever of 100.4°F/38°C or higher, ¡ chills or shivering, ¡ confusion, ¡ dizziness or lightheadedness, ¡ shaking or twitching (tremors), ¡ fast or irregular heartbeat, ¡ severe fatigue, ¡ severe nausea, vomiting, or diarrhea. Do not donate blood, organs, tissues, or cells for transplantation.

Treatment with Abecma may cause a false-positive human immunodeficiency virus (HIV) test result by some commercial tests. Patients treated with Abecma may develop secondary malignancies and should be monitored life-long.

Possible common side effects of Abecma

Tell your doctor immediately if you develop any of these or other symptoms after receiving Abecma. The side effects that occurred in 20% or more patients in the clinical trial include CRS, infections, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy (disease in which the functioning of the brain is affected), edema, fever, cough, headache, and decreased appetite. These are the most common of the possible side effects of Abecma.

Cytokine Release Syndrome (CRS)

Symptoms of CRS, which can be severe or fatal, may include fever, difficulty breathing, dizziness or lightheadedness, nausea, headache, fast heartbeat, low blood pressure, or fatigue. Immediately tell your doctor if you develop any of these symptoms or if you experience any other potential side effects of Abecma.

In patients treated with Abecma in the KarMMa clinical trial, CRS of any grade occurred in 85% of patients using the Lee grading system. The median time to onset of CRS was 1 day after the infusion, and the median duration of CRS was 7 days.

Other Side Effects

Abecma can lower one or more types of your blood cells, which may make you feel weak or tired, or increase your risk of severe infection or bleeding. Abecma can increase the risk of life-threatening infections that may lead to death. Tell your doctor immediately if you develop a fever, are feeling tired, or have bruising or bleeding.

Access to Abecma

Abecma is administered only at certified treatment centers. More information is available at Abecma.com or call 1.888.805.4555.

Abecma is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS); please visit AbecmaREMS.com or call 1.888.423.5436.

In closing

This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team. To help ensure effective treatment with good quality of life, you must play an active role in your own medical care.

We encourage you to visit myeloma.org for more information about myeloma and to contact the IMF InfoLine with your myeloma-related questions and concerns. The IMF InfoLine consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.

Terms and definitions

The following selected terms are used in this booklet, while a more complete compendium of myeloma-related vocabulary can be found in the IMF’s Glossary of Myeloma Terms and Definitions located at glossary.myeloma.org.

Administration-related reaction (ARR): An allergic or cytokine-related response to cancer treatment administered as an intravenous infusion or a subcutaneous injection. See “ Infusion-related reaction (IRR),” “Subcutaneous (SQ) injection,” and “Cytokine.”

Apheresis: Sometimes called leukapheresis, apheresis is a procedure whereby whole blood is taken from a patient or donor, then passed through a machine that separates the blood into its individual components so that one particular component can be collected. The remaining blood components are then immediately re-infused back into the bloodstream of the patient or donor.

Cancer: A term for diseases in which malignant cells divide without control. Cancer cells can invade nearby tissues and spread through the bloodstream and lymphatic system to other parts of the body.

Chimeric antigen receptor (CAR) T-cell therapy: An immunologic treatment approach for hematologic cancers in which a patient’s own T cells are collected and genetically engineered to attack the

Cytokine: Cytokines are proteins secreted by cells which can stimulate or inhibit growth/activity in other cells. Cytokines are produced locally (for myeloma, in the bone marrow) and circulate in the bloodstream. Cytokines are normally released in response to infection.

Cytokine release syndrome (CRS): A potentially fatal, uncontrolled immune reaction in which chemical messengers called cytokines become highly elevated and trigger an overwhelming immune system response. A cytokine storm can seriously damage body tissues and organs. See “Cytokine.”

Grade: The toxicity criteria adopted in the United States by the National Cancer Institute (NCI) for cancer clinical trials includes Grade 0 (no symptoms), Grade 1 (mild symptoms), Grade 2 (moderate symptoms), Grade 3 (symptoms requiring treatment), and Grade 4 (symptoms requiring urgent intervention).

Hypogammaglobulinemia: A laboratory diagnosis made when the immune system is not producing enough immunoglobulin G (IgG) in the blood.

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Immunomodulatory agent: A drug that affects, enhances, or suppresses the immune system. Immunomodulatory drugs are sometimes called IMiD® compounds.

Infusion: Delivering fluids or medications into the bloodstream over a period of time.

Infusion-related reaction (IRR): An IRR is a type of hypersensitivity reaction that develops during or shortly after an intravenous (IV) infusion. IRRs are caused by cytokines and can occur with many IV-administered cancer therapies. Reactions are often flu-like, and include nasal congestion, fever, chills, cough, throat irritation, shortness of breath, low blood pressure, nausea, and rash. See “Administration-related reaction (ARR)” and “Cytokine.”

Intravenous (IV): Administered into a vein.

Minimal residual disease (MRD): The presence of residual tumor cells after treatment has been completed and complete response (CR) has been attained. Even patients who have attained a stringent complete CR (sCR) may have MRD. Very sensitive new testing methods are now able to detect 1 myeloma cell among 1,000,000 sampled cells in blood or bone marrow. See “MRD-negative.”

Monoclonal antibody: An antibody manufactured in a lab rather than produced in the human body. Monoclonal antibodies are specifically designed to find and bind to cancer cells and/or immune system cells for diagnostic or treatment purposes. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to tumor cells.

MRD-negative: Minimal residual disease-negative; not even one myeloma cell found in 100,000 or 1,000,000 bone marrow plasma cells sampled (depending on the test). See “Minimal residual disease.”

Multiple myeloma: A cancer of the bone marrow plasma cells, white blood cells that make antibodies. The cancerous plasma cells are called myeloma cells.

Overall survival (OS): The median number of individuals in a group who are alive after a particular duration of time. OS is often used as a measure of treatment efficacy in clinical trials. The lengthening duration of OS in myeloma trials makes it a difficult endpoint to use, leading to the effort to validate minimal residual disease (MRD) status as a new endpoint.

Progression-free survival (PFS): The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the PFS is one way to determine how well a new treatment works. See “ Progressive disease.”

Progressive disease: Myeloma that is becoming worse or relapsing, as documented by tests. Defined as an increase of ≥ 25% from the lowest confirmed response value in the myeloma protein level and/or new evidence of disease.

Proteasome: A joined group (“complex”) of enzymes (“proteases”) that break down the damaged or unwanted proteins in both normal cells and cancer cells into smaller components. Proteasomes also carry out the regulated breakdown of undamaged proteins in the cell, a process that is necessary for the control of many critical cellular functions. These smaller protein components are then used to create new proteins required by the cell. This is important for maintaining balance within the cell and for regulating cell growth.

Proteasome inhibitor: Any drug that interferes with the normal function of the proteasome. See “ Proteasome.”

Refractory: Disease that is no longer responsive to standard treatments. Patients with refractory myeloma have had progressive disease either during treatment or within 60 days following treatment. Most clinical trials for advanced disease are for patients with relapsed and/or refractory myeloma.

Relapse: The reappearance of signs and symptoms of a disease after a period of improvement. Myeloma patients with relapsed disease have been treated, then developed signs and symptoms of myeloma at least 60 days after treatment ended. Most clinical trials for advanced myeloma are for patients with relapsed and/or refractory disease.

Response or remission: Interchangeable terms to describe the complete or partial disappearance of the signs and symptoms of cancer.

• Stringent complete response (sCR) – sCR is CR (as defined below) plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

• Complete response (CR) – For myeloma, CR is negative immunofixation on serum (blood) and urine, and disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. CR is not the same as a cure.

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• Very good partial response (VGPR) – VGPR is less than CR. VGPR is serum M-protein and urine M-protein detectable by immunofixation but not on electrophoresis, or 90% or greater reduction in serum M-protein, plus urine M-protein less than 100 mg per 24 hours.

• Partial response (PR) – PR is a level of response in which there is at least a 50% reduction in M-protein, and reduction in 24-hour urinary M-protein by at least 90% (or to less than 200 mg per 24 hours).

Side effect: Unwanted effect caused by a drug. Also known as adverse reaction or adverse event (AE).

Subcutaneous (SQ) injection: A method of administering medication under the skin by a short needle that injects a drug into the tissue layer between skin and muscle.

T cells (T lymphocytes): A type of white blood cell that plays a central role in the immune system. T cells can be distinguished from other lymphocytes, such as B cells and natural killer (NK) cells, by the presence of a T-cell receptor (TCR) on the cell surface. They are called T cells because they mature in the thymus (although some also mature in the tonsils).

Connect. Be Informed. Take Charge.

INTERACTIVE

RESOURCES AT A GLANCE

Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF.

infoline.myeloma.org

Contact the IMF InfoLine with your myeloma-related questions and concerns

medications.myeloma.org

Learn about FDA-approved therapies for myeloma

diversity.myeloma.org

Diversity and inclusion are integral aspects of the myeloma community

videos.myeloma.org

The latest on myeloma research and clinical practice, as well as IMF webinars and other events

support.myeloma.org

Robin Tuohy rtuohy@myeloma.org will help you find a multiple myeloma support group

publications.myeloma.org

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