Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. In this disease, abnormal plasma cells, called myeloma cells, multiply rapidly and accumulate, disrupting the production of healthy blood cells. Immunotherapy is a treatment that harnesses the body’s own immune system to fight this cancer.
Understanding Multiple Myeloma and Immunotherapy
Multiple myeloma involves the uncontrolled growth of cancerous plasma cells in the bone marrow. These malignant cells can crowd out healthy blood-forming cells, leading to issues like bone damage, kidney problems, and reduced blood counts. The disease is characterized by abnormal proteins produced by myeloma cells in the blood or urine.
Immunotherapy enhances the patient’s own immune system to target and eliminate cancer cells. It empowers the body’s natural defenses to recognize and destroy abnormal cells, boosting the immune system’s ability to identify cancer as a threat.
How Immunotherapy Fights Multiple Myeloma
Immunotherapy combats multiple myeloma by overcoming how cancer cells evade the body’s natural defenses. Myeloma cells often suppress the immune system, allowing unchecked growth. Immunotherapy aims to reactivate the immune response against these cells.
These therapies target specific proteins on myeloma cells, marking them for destruction. Some block pathways cancer cells use to hide from the immune system. Others enhance the activity of immune cells, such as T-cells, to better recognize and eliminate cancerous plasma cells.
Types of Immunotherapy for Multiple Myeloma
Several categories of immunotherapy are currently utilized in the treatment of multiple myeloma, each with a distinct mechanism of action. These therapies have significantly improved outcomes for patients.
Monoclonal Antibodies
These laboratory-produced proteins attach to specific targets on cancer cells. Daratumumab targets CD38, a protein found on the surface of multiple myeloma cells. Once bound, daratumumab can trigger various immune responses, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), leading to the destruction of myeloma cells. Elotuzumab is another monoclonal antibody that targets SLAMF7 on myeloma cells, enhancing natural killer (NK) cell-mediated killing of these cells. Isatuximab also targets CD38, similar to daratumumab, and is used in combination with other agents.
Bispecific T-cell Engagers (BiTEs)
BiTEs are a newer class of antibodies designed to bring T-cells and myeloma cells into close proximity. These antibodies have two “arms”: one arm binds to a specific protein on the myeloma cell, and the other arm binds to a protein on a T-cell, such as CD3. By bridging these two cell types, BiTEs activate the T-cells, prompting them to directly attack and kill the myeloma cells. Teclistamab, which targets B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T-cells, and Elranatamab, also targeting BCMA and CD3, are examples of approved BiTE therapies.
Chimeric Antigen Receptor (CAR) T-cell Therapy
This therapy modifies a patient’s own T-cells in a laboratory to recognize and attack cancer cells. T-cells are collected from the patient, then genetically engineered to express a CAR that specifically binds to an antigen on the surface of myeloma cells, such as BCMA. These engineered CAR T-cells are then multiplied in the lab and infused back into the patient, where they can seek out and destroy myeloma cells. Idecabtagene vicleucel (ide-cel) and Ciltacabtagene autoleucel (cilta-cel) are two FDA-approved CAR T-cell therapies for multiple myeloma.
Immunomodulatory Drugs (IMiDs)
IMiDs are a class of oral medications that exert their effects by modulating the immune system and directly impacting myeloma cells. These drugs can stimulate the activity of certain immune cells, such as T-cells and natural killer cells, while also inhibiting the growth and survival of myeloma cells. They can also affect the bone marrow microenvironment, making it less hospitable for myeloma cell growth. Lenalidomide and Pomalidomide are widely used IMiDs in multiple myeloma treatment, often in combination with other agents.
What to Expect During Immunotherapy
Undergoing immunotherapy for multiple myeloma involves various practical considerations regarding administration, potential side effects, and monitoring. Many immunotherapies, such as monoclonal antibodies and bispecific T-cell engagers, are typically administered intravenously (IV) through infusions at a clinic or hospital. The duration and frequency of these infusions vary depending on the drug and treatment plan, often ranging from weekly to monthly schedules. Immunomodulatory drugs, in contrast, are taken orally as pills, offering a more convenient administration method. CAR T-cell therapy involves a multi-step process, including cell collection, laboratory modification, and a single infusion, often requiring a hospital stay.
Patients receiving immunotherapy may experience various side effects, which differ based on the specific treatment. Common side effects can include fatigue, nausea, diarrhea, and infusion-related reactions such as fever, chills, or rash. More specific side effects, particularly with CAR T-cell therapy and bispecific antibodies, can include cytokine release syndrome (CRS), which involves an inflammatory response that may cause fever, low blood pressure, and difficulty breathing, and neurotoxicity, which can manifest as confusion or seizures. These more severe side effects are closely monitored and managed with supportive care medications.
Regular monitoring is an important part of immunotherapy treatment to assess the patient’s response and manage side effects. This typically involves blood tests, imaging scans, and bone marrow biopsies at scheduled intervals. The duration of immunotherapy treatment can vary; some therapies are given for a fixed period, while others may continue as long as the patient is responding and tolerating the treatment.