CAR T vs. Stem Cell Transplant for Multiple Myeloma

Since there is currently no cure for multiple myeloma, the goal of treatment is to control the disease and improve your quality of life. For many, this means undergoing CAR T-cell therapy or stem cell transplantation at some point in your journey. While both can effectively lead to treatment response or remission, there are some key differences you should consider.

Both stem cell transplants and CAR T-cell therapy are treatment options for multiple myeloma, though they work in different ways. "Doctors look at your current disease status, treatment history, treatment tolerance, and co-morbidities to identify the safest, most effective option," said Michelle Armstrong, APRN, NP-C, a bone marrow transplant nurse practitioner at Methodist Le Bonheur Healthcare in Memphis, Tennessee.

Stem Cell Transplant

A stem cell transplant, also known as a bone marrow transplant, is a procedure that replaces damaged or destroyed bone marrow with healthy stem cells. These stem cells can come from your own body (autologous transplant) or from a donor (allogeneic transplant).

In multiple myeloma, a stem cell transplant can restore your body's ability to produce healthy blood cells after high-dose chemotherapy. Your stem cells are collected, frozen, and then returned to your body after undergoing chemotherapy. The goal is to replenish your bone marrow with healthy cells that can continue to produce new blood cells.

There are several risks associated with a stem cell transplant, including infections, graft-versus-host disease (GVHD) in allogeneic transplants, and long recovery periods with possible fatigue or organ damage. "There is also a small risk of secondary cancers due to the chemotherapy used in the procedure," said Wael Harb, MD, a board-certified hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast and Saddleback Medical Centers in Orange County, California.

CAR T-Cell Therapy

CAR T-cell therapy is short for chimeric antigen receptor T-cell therapy. "[It] directly targets cancer cells using the patient’s genetically engineered T cells," said Dr. Harb. Unlike stem cell transplants, CAR T-cell therapy doesn't involve replacing bone marrow. Instead, it focuses on "reprogramming" your immune system to target and kill cancer cells.

Your T-cells are collected from your blood and modified in a laboratory to express chimeric antigen receptors (proteins that enable the T-cells to identify and attack cancer cells). The altered cells are infused back into your body, where they bind to and kill myeloma cells.

Like stem cell transplants, CAR T-cell therapy carries risks. The most common is cytokine release syndrome (CRS), a reaction resulting from the release of immune proteins. Symptoms include fever, low blood pressure, and difficulty breathing. Neurological side effects, such as confusion or memory problems, can also occur.

A stem cell transplant is used to replace the damaged marrow with healthy stem cells. It's a way to ensure your bone marrow continues producing new, healthy blood cells.

Stem cell transplants are also sometimes used as a treatment option for relapsed or refractory multiple myeloma (when cancer has not responded to previous treatments). If your first autologous transplant provides a successful period of remission, you may be eligible for a second transplant.

CAR T-cell therapy, on the other hand, is a more targeted approach to treating multiple myeloma. "It's reserved for relapsed or refractory multiple myeloma, where other treatments, including stem cell transplant, have failed," Dr. Harb said.

There are currently two FDA-approved CAR T-cell therapies for multiple myeloma:

• Idecabtagene vicleucel (Abecma), also called ide-cel

• Ciltacabtagene autoleucel (Carvykti), also called cilta-cel

Both work by targeting a protein called B-cell maturation antigen (BCMA) on the myeloma cells.

While you won't be eligible for CAR T-therapy unless you have already relapsed after prior treatment, many people with multiple myeloma eventually have both a stem cell transplant and CAR T-cell therapy.

"Often, these treatments are used as a bridge to get to the other one, meaning that a patient will proceed with CAR-T to get their multiple myeloma under control in order to qualify for a stem cell transplant and achieve maximum benefit," said Armstrong. "Combined, they can lead to more years of progression-free survival."

A stem cell transplant is typically recommended for those with multiple myeloma who are under the age of 70 and are in good overall health. Candidates should not have any medical conditions that could make chemotherapy or the transplant more dangerous, such as heart, lung, and kidney disease. People over age 70 or with extensive health issues may not be able to withstand the intense chemotherapy required for a stem cell transplant.

For CAR T-cell therapy with cilta-cel, candidates must have relapsed or refractory multiple myeloma, have already undergone at least one prior therapy with a proteasome inhibitor and immunomodulatory agent, and must be refractory to lenalidomide.

With ide-cel, candidates must have had at least two prior treatments, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Success rates vary, said Abhinav Deol, MD, a hematologist and medical oncologist and member of the Bone Marrow and Stem Cell Transplant Multidisciplinary Team at Barbara Ann Karmanos Cancer Institute. Since the treatments are used at different stages of multiple myeloma and in different types of patients (those with relapsed or refractory disease versus those who haven’t yet had treatment), it’s tough to make a direct comparison.

"With autologous stem cell transplantation, we recommend undergoing the procedure early during therapy as it helps prolong how long the disease may stay under control," said Dr. Deol. With maintenance therapy, the duration of response to a transplant is often more than four years. "The response rate of anti-BCMA CAR T-cell therapy is around 80%-90%."

According to 2024 research published in the journal Blood, cilta-cel had an overall response rate of 84.6%, while ide-cel had an overall response rate of 71% in people with relapsed refractory multiple myeloma (RRMM).

Additionally, recent data from the 66th American Society of Hematology Annual Meeting and Exposition has shown that 100% of patients with high-risk smoldering multiple myeloma achieved complete response after receiving cilta-cel therapy.

"There is an ongoing study comparing autologous stem cell transplant and CAR T-cell therapy for first-line treatment, which may show if one therapy is better than the other when compared directly," said Dr. Deol. While multiple myeloma is currently incurable, researchers are getting closer to finding more effective first-line treatment options and potentially a cure in the future.

Both therapies can help you achieve remission, but they work differently and are used at different stages. Stem cell transplant may be recommended as a first-line treatment following chemotherapy, while CAR T-cell therapy is typically reserved for relapsed or refractory multiple myeloma.

"With multiple myeloma, relapses and disease progression are expected and can happen quickly, but with both of these treatment modalities, there is a benefit for longer progression-free survival," said Armstrong. Even if a complete remission is not achieved, these treatments can help control the disease and improve your quality of life.