MMRF Immunotherapy Initiative: Chimeric Antigen Receptor (CAR) T-Cell Therapy

The most exciting area of myeloma research is immunotherapy. Cancer immunotherapy is a type of treatment that uses a patient’s immune system to fight cancer. For myeloma immunotherapy treatments to work, they must be designed to recognize myeloma cells…so they can destroy them. This has long been a challenge, because myeloma cells—like all cancer cells—have a couple of tricks up their proverbial sleeves. One such trick is the ability to hide from the body’s normal immune response. Another is the ability to weaken the body’s immune response to such an extent that they—that is, the myeloma cells—can continue to grow and thrive in a patient.

There are many types of immunotherapies that can rev up or improve a patient’s immune response. In fact, one class of immunotherapy is already used in myeloma treatment—the monoclonal antibodies. These comprise Darzalex and Empliciti.

Another class of immunotherapy, called cell-based therapy or cellular therapy, is capturing headlines because of its ability to induce responses in most patients—even those that have relapsed from many prior therapies. One form of cellular therapy is called chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy has already been approved for patients with certain types of leukemias and lymphomas and is being studied in patients with myeloma.

CAR T-cell therapy involves removing a patient’s white blood cells (which includes T cells), which is similar to the procedure (stem cell harvest) performed before an autologous stem cell transplant. T cells, which circulate through the body, are important in fighting infections and searching the body for cancer. When cancer cells are detected, T cells are able to kill them. The T cell grabs hold of the cancer cell and then pumps toxins into it.

But, as noted above, cancer cells have found ways to avoid being detected and grabbed by T cells. In CAR T-cell therapy, regular/normal T cells are “supercharged,” which helps them see myeloma cells—even when they’re hiding. The process of “supercharging” the T cells involves extracting them from a myeloma patient, making genetic changes to them in a lab (turning them into more effective myeloma detectors and killers!), and then re-infusing them into the patient. Once back inside the patient, the improved T cells (that is, CAR T cells) resume their search-and-destroy mission against myeloma cells.

Most of the cells used in the CAR T-cell therapies that are under investigation have been genetically changed to latch onto a specific protein (called the B-cell maturation antigen, or BCMA) found on the surface of most myeloma cells. Some of the BCMA-modified CAR T-cell therapy agents currently being studied in patients with relapsed myeloma are listed below. You may see reports about these in the news or hear about them at scientific meetings or from your myeloma doctor:

  • bb2121
  • bb21217
  • LCAR-B38M
  • CT053
  • JCARH125
  • MCARH171
  • P-BCMA-101

In clinical trials, all the BCMA-modified CAR T-cell therapies being studied in myeloma patients have produced high response rates. However, most patients have been found to experience a common side effect called cytokine release syndrome (CRS), which is an infection-like syndrome in which a patient experiences fevers, chills, and low blood pressure after the infusion of CAR T cells. The cause of CRS is thought to be from the growth of the CAR T cells and the resulting surge in the immune response, which is mainly driven by a cytokine (a protein that is produced by immune cells) called interleukin-6 (IL-6). Fortunately, there is a drug called tocilizumab that interferes with IL-6 and can stop CRS.

Patients treated with CAR T cells also exhibited some nervous system side effects. Some patients experience mild symptoms like confusion, but in some cases patients experience severe symptoms like delirium or seizures. These side effects were less common and less understood than CRS, and most resolved over time. However, these nervous system side effects remain an issue and are under study.

In addition to side effects, a challenge of CAR T-cell therapy is getting the “supercharged” T cells to remain in the body. They tend to disappear over time, and even patients who had an initial response may relapse. Strategies to improve CAR T-cell immune protection in myeloma patients are being studied with the help of the MMRF Immunotherapy Initiative. Through this initiative, the MMRF has provided funding to Dr. David Avigan at Beth Israel Deaconess Medical Center to determine whether a cancer vaccine can activate CAR T-cells enough so that they don’t disappear.

In clinical trials, CAR T-cell therapy has shown encouraging responses. These studies are ongoing, as researchers compare different agents in an attempt to determine how long responses last, the maximum number of cells that need to be infused into patients, and whether certain agents are associated with less CRS and fewer nervous system side effects.

To learn more about CAR T-cell therapy, you can listen to Dr. Edward Stadtmauer of UPenn speak about the latest developments in the field on our recent MMRF webinar at https://event.webcasts.com/starthere.jsp?ei=1233305&tp_key=298299e0d1. If you have more questions or want to know if a CAR T-cell therapy trial is available near you—you can contact a Nurse Patient Navigator at the MMRF Patient Support Center at 866-603-6628.

 

Additional Resources

MMRF. 2018 Patient Webinars. CAR T-Cell Therapy for Multiple Myeloma.

MMRF. ASH 2018 Day 3 – Immunotherapy.

MMRF. Clinical trials and experimental therapies.

MMRF. Multiple Myeloma Research Foundation (MMRF) Awards $7 Million to Advance Cutting-edge Immunotherapy Initiative [press release]. March 27, 2018.