Bristol Myers Squibb, a global biopharmaceutical company, recently disclosed that a patient enrolled in an early-stage trial of its experimental CAR-T cell therapy for multiple sclerosis had died, Reuters and other news outlets reported.
The patient died of septic pneumonia a day after receiving high-dose chemotherapy and 44 days after an infusion of the treatment, zolacabtagene autoleucel, or zola-cel. The death occurred after the company had implemented a voluntary pause on studies of the treatment to review safety data. Bristol Myers Squibb said the patient’s death was unrelated to its earlier decision to pause the studies, according to Reuters.
Meanwhile, Novartis began initiating holds on clinical trials of a different CAR-T therapy, rapcabtagene autoleucel, for several autoimmune diseases, in August. The program recorded three deaths from complications caused by serious immune effector cell-associated hemophagocytic syndrome, a severe systemic inflammatory side effect, according to Fierce Biotech.
Several CAR-T cell therapies are approved and have shown strong success in cancers, but studies for autoimmune diseases are ongoing. This tip sheet provides journalists with more information about this therapy.
More about CAR-T cell therapy
CAR-T cell therapy (chimeric antigen receptor T-cell therapy) is a personalized form of immunotherapy that trains a person’s immune cells to recognize and destroy specific cell types, the American Cancer Society explains. In cancer treatments, it helps immune cells target proteins on cancer cells.
The therapy, given as a one-time treatment, involves several steps, according to Yale Medicine, the American Cancer Society, and other sources. First, clinicians collect a patient’s immune system T cells through an outpatient procedure that filters the cells from the bloodstream. Then, scientists genetically modify the T cells in a lab to add a chimeric antigen receptor (CAR) on their surface, so they attach to a protein called an antigen on a specific target cell. In blood cancers, the target is on the cancer cells; in autoimmune diseases, the target is on immune cells driving the disease. Researchers grow these modified cells for a few weeks until there are enough for treatment.
Before treatment, patients typically undergo chemotherapy to prevent their immune system from blocking the modified T cells and to make room for new cells to grow. The CAR-T cells are then infused back into the patient.
Who it’s approved for and number of exisiting therapies
The FDA in August 2017 approved the first CAR T-cell therapy, Kymriah (tisagenlecleucel), for the treatment of patients up to age 25 who have B-cell precursor acute lymphoblastic leukemia (a type of blood/bone marrow cancer) who haven’t responded to standard therapies or who have relapsed at least twice, according to an article in Cancer Discovery.
Seven therapies are now approved for blood cancers, including acute lymphoblastic leukemia (ALL), large B cell lymphoma, mantle cell lymphoma, and multiple myeloma, according to the Alliance for Cancer Gene Therapy.
The other products are:
- Yescarta (axicabtagene ciloleucel), for two types of non-Hodgkin lymphoma
- Tecartus (brexucabtagene autoleucel), for mantle cell lymphoma or acute lymphoblastic leukemia
- Breyanzi (lisocabtagene maraleucel), for four types of non-Hodgkin lymphoma
- Abecma (idecabtagene vicleucel), for multiple myeloma
- Carvykti (ciltacabtagene autoleucel), for multiple myeloma
- Aucatzyl (obecabtagene autoleucel), for B-cell precursor acute lymphoblastic leukemia
Side effects
The downside to this therapy is that patients who receive it are at risk for serious and potentially life-threatening side effects, the Cancer Discovery article noted. This includes allergic reactions, a weakened immune system that puts patients at risk for infections, and low blood cell counts that may cause fatigue or bruising, according to MD Anderson Cancer Center. Close follow-up is essential to detect and manage these reactions.
Serious side effects include:
- Cytokine release syndrome, which can happen as CAR-T cells multiply and release large amounts of chemicals into the blood, ramping up the immune system. This can lead to high fever and chills, severe nausea and vomiting, headaches, fatigue and a fast heartbeat, according to the American Cancer Society.
- Immune effector cell-associated neurotoxicity syndrome (ICANS) is a neurological condition that can occur after CAR T-cell therapy. It is caused by inflammation affecting the brain and central nervous system, according to Cancer Research UK.
- When CAR T cells are engineered to target B cells, the number of cancerous and healthy B cells in the body can drop, putting a person at risk of B-cell aplasia, according to Dana-Farber Cancer Institute.
- The conditioning chemotherapy and CAR T-cell therapy can destroy a large amount of tumor, and when these cancer cells die, the contents are released into the bloodstream. This can result in tumor lysis syndrome, when shifts of fluid and minerals occur, and can lead to kidney damage, according to the Dana-Farber Cancer Institute.
Other conditions/diseases CAR-T is being evaluated for
The therapy is being tested in clinical trials to treat a variety of autoimmune diseases, including lupus, multiple sclerosis, and scleroderma, according to Yale Medicine. In these diseases, the immune system attacks the body’s healthy tissues. Researchers are studying whether CAR-T can remove the specific immune cells driving disease, possibly leading to longer-lasting control than current treatments that calm or suppress the immune system and often must be taken long term.
Expert sources to interview
Oncologists, representatives from cancer organizations or societies, such as the American Society of Clinical Oncology, or rheumatologists and representatives from rheumatology organizations like the American College of Rheumatology for stories on autoimmune disease.
Potential story ideas
- Talk to patients who have had CAR-T cell therapy to see how they fared.
- Write about how the therapy is expanding into other diseases and why it has been challenging in the autoimmune space.
- Write about next-generation designs of CAR-T therapies in development, like those with multiple targets.
- Write about how this therapy has shifted from inpatient to outpatient administration.
Resources
Bristol Myers discloses patient death in early-stage cell therapy study – Reuters
Patient dies in Bristol Myers Squibb autoimmune CAR-T trial – STAT
Novartis halts autoimmune CAR-T trials after 3 deaths, as BMS also pauses studies – Fierce Biotech
CAR T cells: Engineering patients’ immune cells to treat their cancers – National Cancer Institute
First-ever CAR T-cell therapy approved in U.S. – Cancer Discovery
CAR-T cell therapy moves beyond cancer to autoimmune diseases – Yale Medicine
CAR T-cell therapy and its side effects – American Cancer Society
