BCMA CAR-T therapy is a personalized immunotherapy for multiple myeloma. This treatment genetically modifies a patient’s T-cells to recognize and eliminate cancer cells. BCMA (B-cell maturation antigen) is a protein found on multiple myeloma cells, making it a suitable target. The therapy is considered for individuals whose multiple myeloma has returned or has not responded to previous treatments. It offers a way to target drug-resistant myeloma cells, providing a significant advancement in treatment.
The Mechanism of BCMA CAR-T
BCMA is a protein found in high concentrations on malignant plasma cells, the cancerous cells in multiple myeloma. Its presence on healthy tissues is limited, making it an attractive target. BCMA also plays a role in myeloma cell growth and survival.
T-cells are immune cells that identify and destroy abnormal cells. In BCMA CAR-T therapy, T-cells are engineered to express a Chimeric Antigen Receptor (CAR) on their surface. This synthetic receptor is designed to specifically bind to BCMA on myeloma cells.
The engineering transforms T-cells into “hunter” cells. Once infused, these modified CAR-T cells recognize and attach to BCMA on myeloma cells. This binding activates the CAR-T cells, enabling them to multiply and destroy cancer cells throughout the body.
The Patient Treatment Process
BCMA CAR-T therapy begins with leukapheresis, where a patient’s T-cells are collected from their blood. This process is similar to a blood donation, using a machine to separate and collect white blood cells while returning the remaining blood components to the patient. The procedure typically takes about four hours.
Following collection, T-cells are sent to a specialized manufacturing facility for genetic engineering. In the laboratory, the cells are modified to express the Chimeric Antigen Receptor (CAR) that targets BCMA, effectively turning them into CAR-T cells. This complex manufacturing step can take several weeks, usually ranging from three to five weeks, during which time the patient may receive temporary “bridging” therapy to help control their myeloma.
Just before the CAR-T cell infusion, patients undergo a brief course of lymphodepleting chemotherapy, typically using drugs like cyclophosphamide and fludarabine. The purpose of this chemotherapy is not to directly treat the myeloma, but to reduce the number of existing lymphocytes in the patient’s body. This creates a more favorable environment for the newly infused CAR-T cells to multiply, persist, and effectively target the cancer.
The modified CAR-T cells are then infused back into the patient, a process often resembling a standard blood transfusion. After the infusion, patients are closely monitored, typically for at least 30 days, to watch for any potential side effects. This initial monitoring period may involve inpatient hospital stays, often for the first one to two weeks, followed by outpatient monitoring where the patient remains close to the treatment center.
Potential Side Effects and Management
BCMA CAR-T therapy can lead to specific side effects that require careful monitoring and management by specialized medical teams. One common side effect is Cytokine Release Syndrome (CRS), which is an inflammatory response caused by the activated CAR-T cells releasing signaling proteins called cytokines as they destroy cancer cells. Symptoms of CRS can range from mild, flu-like symptoms such as high fever and fatigue, to more severe manifestations like low blood pressure, difficulty breathing, and organ dysfunction. The severity of CRS is graded, and mild cases are managed with supportive care, while more severe cases may require medications like tocilizumab, which blocks interleukin-6, a key cytokine involved in CRS.
Another potential side effect is Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which involves neurological symptoms. ICANS can manifest as confusion, difficulties with language, tremors, or headaches. Although it can be concerning, ICANS is typically reversible. Patients are closely monitored for these neurological changes, often through simple assessments like evaluating their orientation, attention, and ability to write. Management of ICANS often involves supportive care and corticosteroids, such as dexamethasone, with the dosage and timing adjusted based on the severity of symptoms.
Other potential issues include cytopenias, which are low blood cell counts, such as anemia (low red blood cells), neutropenia (low neutrophils, a type of white blood cell), and thrombocytopenia (low platelets). These cytopenias can increase the risk of infections and bleeding. While often attributed to the lymphodepleting chemotherapy, prolonged cytopenias can also result from the therapy’s impact on bone marrow and inflammatory responses. Healthcare teams carefully manage these conditions, sometimes with growth factors, transfusions, or immunoglobulins to help the patient recover.
Treatment Outcomes and Approved Therapies
BCMA CAR-T therapies have shown high response rates in patients with relapsed or refractory multiple myeloma. Clinical trials have reported overall response rates (the percentage of patients whose cancer shrinks or disappears) ranging from 73% to 98%. A significant proportion of patients also achieve a complete response, meaning there are no detectable signs of cancer, with rates as high as 78% to 82.5% in some studies.
The concept of “depth of response” is also important, referring to how completely the cancer is eliminated. Many patients achieve minimal residual disease (MRD) negativity, indicating that very few, if any, myeloma cells remain in the bone marrow, often at a sensitivity of 1 in 100,000 or 1 in a million cells. Achieving MRD negativity has been associated with longer progression-free survival, meaning the period during which the disease does not worsen.
Two specific BCMA CAR-T products have received approval from the U.S. Food and Drug Administration (FDA) for multiple myeloma. Idecabtagene vicleucel, marketed as Abecma, was approved for patients who have received at least two prior lines of therapy, including specific classes of drugs. Ciltacabtagene autoleucel, known by the brand name Carvykti, is approved for patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.
While these therapies offer durable remissions for many patients, with some individuals remaining progression-free for five years or more, relapse is still possible. Research continues to explore ways to improve the long-term effectiveness of these therapies and to develop strategies for patients who experience relapse after BCMA CAR-T treatment. This includes investigating new targets and combination therapies to overcome potential resistance mechanisms.