Immunotherapy for Multiple Myeloma

Immunotherapy for multiple myeloma is a form of treatment that harnesses the natural ability of the body’s immune system to recognize and attack cancerous plasma cells. Several types of immunotherapy are available for multiple myeloma, ranging from antibodies that target specific proteins on myeloma cells to cellular therapies that modify the patient’s own immune cells to fight the disease.

Some forms of immunotherapy may be incorporated into the initial treatment plan for newly diagnosed multiple myeloma, while other forms are primarily used when myeloma returns or does not respond to previous treatment. Although multiple myeloma is generally not considered curable, immunotherapy can significantly expand the treatment options for certain patients and, in some cases, produce a deep, durable response.

Goals of immunotherapy for multiple myeloma

Immunotherapy can serve different purposes in multiple myeloma treatment depending on the type of therapy, the status of the disease, any treatments the patient has already received and the overall care plan. Its role may be to:

• Treat newly diagnosed multiple myeloma – Certain monoclonal antibodies can be combined with other myeloma medications as part of initial therapy. For example, daratumumab may be incorporated into a regimen containing a proteasome inhibitor, an immunomodulatory drug and dexamethasone.
• Control relapsed or refractory disease – If multiple myeloma returns after treatment or stops responding to therapy, immunotherapy may provide another way to attack the cancer. Options may include monoclonal antibodies, bispecific antibodies and CAR T-cell therapy, depending on the patient’s prior treatments and other factors.
• Achieve a deep and durable response – Some immunotherapies can substantially reduce the number of myeloma cells in the body and produce a period of remission. The duration of the response can vary considerably among patients and treatments.
• Provide another treatment option when previous therapies are no longer effective – The expanding range of immune-based therapies may give the healthcare team additional options to consider if myeloma becomes resistant to one or more previous treatments.

Types of immunotherapy for multiple myeloma

Immunotherapy for multiple myeloma encompasses several distinct treatment approaches. The healthcare team will select a therapy based on current clinical guidelines, the characteristics of the myeloma and the patient’s previous treatments and overall health. Options may include:

Monoclonal antibodies for multiple myeloma

Monoclonal antibodies are laboratory-made proteins designed to recognize specific targets on cancer cells. Once attached to a target, an antibody may interfere with the cancer cell’s survival while helping the immune system identify and destroy it.

Several monoclonal antibodies may be used in multiple myeloma treatment, including:

• Daratumumab (Darzalex/Darzalex Faspro) and isatuximab (Sarclisa/Sarclisa Escena) – These drugs target CD38 on myeloma cells, helping the immune system recognize and destroy the cancer, and may be used for newly diagnosed or previously treated disease.
• Elotuzumab (Empliciti) – This drug targets SLAMF7 on myeloma cells, helping the immune system identify and attack the cancer, and may be used in certain treatment combinations for previously treated multiple myeloma.

Bispecific antibodies for multiple myeloma

Bispecific antibodies are engineered to bind to two different targets at the same time. In multiple myeloma, one part of the antibody attaches to a protein on a myeloma cell and the other attaches to CD3 on a T cell. Bringing the two cells together activates the T cell against the cancer.

Several bispecific antibodies may be used for certain patients with relapsed or refractory multiple myeloma, including:

• Teclistamab (Tecvayli) – Targets BCMA on myeloma cells and CD3 on T cells
• Elranatamab (Elrexfio) – Also targets BCMA and CD3
• Talquetamab (Talvey) – Targets GPRC5D on myeloma cells and CD3 on T cells

The approved uses of these medications continue to evolve. For example, teclistamab in combination with daratumumab received FDA approval in 2026 for certain patients who have received at least one previous treatment regimen for multiple myeloma. 

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CAR T-cell therapy for multiple myeloma

Chimeric antigen receptor (CAR) T-cell therapy is an individualized form of cellular immunotherapy. Through a process known as leukapheresis, T cells are collected from the patient’s blood and sent to a specialized laboratory, where they are genetically modified to produce receptors that recognize a certain protein on myeloma cells. After being multiplied, the modified cells are reinfused into the patient’s bloodstream, where they can seek out and attack the cancer.

FDA-approved CAR T-cell therapies for multiple myeloma include idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti). Both target BCMA and are used for certain patients with relapsed or refractory disease. Moffitt continues to evaluate new CAR T-cell approaches through clinical trials.

What to expect before, during and after immunotherapy for multiple myeloma

Because immunotherapy encompasses several different treatments, the experience of receiving it can vary substantially. An antibody therapy given in an outpatient setting, for example, involves a different process than CAR T-cell therapy. The healthcare team will explain the recommended treatment, how it will be administered and what monitoring will be necessary.

Preparing for immunotherapy for multiple myeloma

Before treatment begins, the patient will undergo an evaluation to determine whether a particular immunotherapy is appropriate. This may include a review of previous treatments and their effectiveness, blood and urine tests, bone marrow testing, imaging and an assessment of the patient’s overall health and organ function.

The healthcare team may include hematologist-oncologists, cellular therapy specialists, specialized nurses, clinical pharmacists and other professionals. Additional testing and preparation will be necessary for CAR T-cell therapy because the patient’s T cells must be collected and genetically modified before treatment.

What to expect on treatment days

The treatment process can vary considerably based on the specific immunotherapy being given. Monoclonal and bispecific antibodies may be administered intravenously or as an injection under the skin. Typically, the healthcare team will check the patient’s vital signs and laboratory results and may give medications beforehand to reduce the likelihood or severity of certain reactions.

Some bispecific antibodies require gradually increasing the initial dose, a process known as step-up dosing, with close monitoring for cytokine release syndrome (CRS), an inflammatory reaction caused by rapid immune system activation, and neurologic effects.

CAR T-cell therapy follows a different process. After the modified T cells are manufactured, the patient usually receives a short course of lymphodepleting chemotherapy to prepare the body for the cells. The CAR T cells are then returned to the bloodstream through an intravenous infusion. Because CAR T-cell therapy can cause potentially serious immune reactions, the patient will require specialized monitoring before and after the infusion.

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The immunotherapy schedule

There is no single immunotherapy schedule for multiple myeloma. Some antibody treatments are administered repeatedly according to a schedule that may become less frequent over time. CAR T-cell therapy generally involves one infusion of the manufactured cells following the collection and preparation process.

Regardless of the treatment schedule, follow-up is an important part of immunotherapy. The healthcare team will monitor the patient’s blood counts, organ function, treatment response and side effects and adjust supportive care or treatment when necessary.

Possible side effects of immunotherapy for multiple myeloma

Because the immunotherapies used for multiple myeloma have distinct safety profiles, side effects can vary. For example, monoclonal antibodies can cause administration-related reactions, while T-cell-engaging therapies such as bispecific antibodies and CAR T cells can trigger CRS and neurologic effects. Promptly reporting new or worsening symptoms is important because many treatment-related side effects can be managed more effectively when recognized early.

Common side effects and proactive management

Possible effects of myeloma immunotherapy include:

• Administration-related reactions – Monoclonal antibody treatments can cause reactions such as fever, chills, congestion, cough, nausea or shortness of breath, particularly with early doses. Pretreatment medications and careful monitoring can help prevent or manage these reactions.
• Cytokine release syndrome – CAR T-cell therapies and bispecific antibodies can activate large numbers of T cells and cause a surge of inflammatory signaling molecules known as cytokines. Symptoms can include fever, chills, fatigue, low blood pressure or difficulty breathing. The healthcare team will closely monitor for CRS and can provide medications and supportive care when needed.
• Neurologic effects – Some T-cell-directed therapies can affect the nervous system. Confusion, difficulty speaking, unusual sleepiness, tremors or other new neurologic symptoms should be reported immediately.
• Low blood cell counts – Treatment can reduce the levels of white blood cells, red blood cells or platelets. Regular blood testing can allow the healthcare team to identify any changes and provide appropriate supportive care.
• Infections – Multiple myeloma itself can impair immune function, and some immunotherapies can further increase infection risk. The healthcare team may recommend preventive medications, immunoglobulin replacement or other precautions for some patients.
• Fatigue – Tiredness is common during cancer treatment. Balancing gentle activity with planned periods of rest, maintaining adequate nutrition and discussing persistent or worsening fatigue with the healthcare team can help.

Certain therapies have additional characteristic effects. For example, talquetamab can cause skin and nail changes as well as changes in taste. The healthcare team will discuss any risks specific to the treatment being considered.

Possible long-term and late-onset side effects

Some effects of immunotherapy may persist or emerge after active treatment. Depending on the therapy, these may include:

• Prolonged low blood cell counts – Blood counts may remain low after CAR T-cell therapy, requiring continued laboratory monitoring and sometimes supportive treatment.
• Persistent immune suppression – Some therapies can reduce normal antibody levels and increase susceptibility to infection. The patient may require ongoing monitoring and preventive measures.
• Delayed neurologic effects – Certain neurologic complications may occur after CAR T-cell therapy, making continued follow-up and prompt reporting of new symptoms important.
• Secondary cancers – CAR T-cell therapy carries a risk of developing another cancer, so long-term follow-up is an important part of care.

The risks differ by treatment, and experiencing a particular side effect does not mean it will become permanent. The healthcare team will explain what to watch for based on the specific therapy the patient receives.

Managing daily life during immunotherapy for multiple myeloma

The impact of immunotherapy on daily activities can vary by treatment and the patient’s response. Practical steps that can help support well-being during immunotherapy include:

• Report symptoms promptly – Fever, breathing difficulty, confusion, severe weakness or other new or rapidly worsening symptoms should be reported according to the healthcare team’s instructions. If the patient is receiving CAR T-cell or bispecific antibody therapy, the patient will receive specific guidance about symptoms that require urgent attention.
• Support good nutrition and hydration – Eating a balanced diet and drinking enough fluids can help support the body during immunotherapy. Moffitt’s registered dietitians can help the patient address appetite changes, taste changes or other nutritional concerns.
• Reduce infection risk – Because multiple myeloma and its treatment can weaken the body’s immune defenses, the patient should follow the healthcare team’s recommendations for infection prevention and promptly report any signs of illness.
• Stay active when appropriate – Gentle, regular physical activity can help preserve strength and may reduce treatment-related fatigue. The appropriate type and intensity of activity can vary depending on factors such as the patient’s bone health, blood counts and overall condition.
• Use supportive care resources – Counseling, rehabilitation, nutrition services and other supportive resources can help address the physical and emotional effects of cancer and its treatment.

Immunotherapy clinical trials for multiple myeloma at Moffitt Cancer Center 

Immunotherapy is one of the most rapidly advancing areas of multiple myeloma research. Through clinical trials, scientists and clinicians are investigating how established immune-based treatments can be used more effectively, as well as entirely new approaches to directing the body’s immune system against myeloma.

Moffitt has an active multiple myeloma clinical trials program that includes research involving bispecific antibodies and next-generation CAR T-cell therapies. Current studies are exploring therapies that target more than one protein on myeloma cells and ways to use T-cell-directed therapies at different points in the treatment course.

Moffitt has extensive experience with cellular immunotherapy. Our cancer center was the first in the world to treat more than 2,000 patients with CAR T-cell therapy and has helped lead clinical trials that contributed to FDA approvals of CAR T-cell therapies for several cancers, including multiple myeloma. For an eligible patient, participation in a clinical trial may provide access to an investigational immunotherapy or treatment combination that is not yet widely available.

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Frequently asked questions (FAQs) about immunotherapy for multiple myeloma 

As immunotherapy options for multiple myeloma continue to expand, the patient may encounter unfamiliar terms and treatment approaches. The following answers address several common questions.

How is immunotherapy different from traditional chemotherapy for multiple myeloma?

Traditional chemotherapy directly damages rapidly dividing cells, including cancer cells. Immunotherapy instead uses or redirects components of the immune system to attack myeloma cells, often by recognizing specific proteins on the surface of the cells. Because these treatments work differently, their side effects also can differ.

How does CAR T-cell therapy work for a patient with relapsed multiple myeloma?

CAR T-cell therapy begins by collecting T cells from the patient’s blood. The collected cells are then genetically modified to recognize a target on myeloma cells, multiplied and infused back into the patient. Once in the body, the modified T cells can identify and attack cells carrying that target.

What are bispecific antibodies, and how do they target myeloma cells?

Bispecific antibodies are designed to attach to two targets simultaneously. In multiple myeloma, these drugs typically bind to CD3 on a T cell and to a target such as BCMA or GPRC5D on a myeloma cell, bringing the cells together so the T cell can attack the cancer.

What are the potential immune-related side effects of multiple myeloma immunotherapy?

The risks depend on the type of immunotherapy administered. CAR T-cell therapies and bispecific antibodies can cause CRS, neurologic effects, low blood cell counts and infections, while monoclonal antibodies may cause administration-related reactions and other treatment-specific effects. Close monitoring and early symptom reporting help the healthcare team identify and manage complications.

Can immunotherapy cure multiple myeloma?

Multiple myeloma generally is not considered curable, so immunotherapy cannot currently be described as a cure. However, some immunotherapies can produce a deep and long-lasting response in some patients, including a period when no measurable disease can be detected with highly sensitive testing.

Is immunotherapy used as a first-line treatment for multiple myeloma?

Yes, certain forms are. Anti-CD38 monoclonal antibodies such as daratumumab and isatuximab may be included in a treatment regimen for newly diagnosed multiple myeloma. Other immunotherapies, including currently approved CAR T-cell therapies and many bispecific antibody regimens, are generally used after one or more previous treatments, although clinical trials are evaluating these approaches earlier in the course of disease.

The Moffitt Cancer Center approach to immunotherapy for multiple myeloma

At Moffitt, multiple myeloma treatment is individualized through a multispecialty approach that brings together experts in malignant hematology, cellular immunotherapy and other areas of cancer care. When determining whether immunotherapy should be part of the care plan, our team considers the biological characteristics of the disease as well as the patient’s treatment history, response to previous therapy, overall health and treatment goals.

Moffitt is the only National Cancer Institute (NCI)-designated Comprehensive Cancer Center based in Florida, and we have established a major cellular therapy program. Our specialists continue to investigate next-generation cellular and immune-based treatments through a robust portfolio of clinical trials. This combination of clinical expertise and active research provides our patients with access to established immunotherapies as well as opportunities to be considered for emerging approaches that may not yet be widely available.

To learn more about immunotherapy for multiple myeloma, you can request an appointment with a specialist in Moffitt’s Malignant Hematology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.