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New Treatment Options for Relapsed or Refractory Myeloma

Medically reviewed by Todd Gersten, M.D.
Written by Maureen McNulty
Posted on December 13, 2022

  • Researchers are continually developing treatment options that may lead to better outcomes for people with relapsed or refractory multiple myeloma (RRMM).
  • Many of the latest drugs can more accurately target myeloma cells by attaching to specific molecules found on these cells.
  • Newer types of immunotherapy options can also help strengthen the immune system to fight myeloma.

In recent decades, researchers have developed many therapies for multiple myeloma that can more effectively treat this blood cancer and help people live longer. These advances have made a huge impact on prognosis for people living with myeloma.

According to the Multiple Myeloma Research Foundation, in 1998, only about 35 percent of people were expected to live for five years or more after being diagnosed with myeloma. The most recent National Cancer Institute data, which includes those diagnosed between 2012 and 2018, shows that 58 percent of people survive myeloma for at least five years.

People receiving a myeloma diagnosis today likely have even better survival rates, thanks to cutting-edge treatments that were developed in the past couple of years. Although multiple myeloma usually relapses (returns after being treated) and often becomes refractory (resists previously used treatments), new therapies can help control the growth of cancerous myeloma cells for longer and longer periods.

Monoclonal Antibodies

The immune system produces antibodies, proteins that help recognize harmful substances such as bacteria, viruses, and cancer cells. Once an invader is found, healthy antibodies attach to these invaders and signal immune cells to help destroy the target.

Monoclonal antibodies are made in a laboratory. These molecules are often used as cancer drugs because they can help the immune system find and kill cancer cells or prevent their growth.

One common monoclonal antibody used to treat myeloma is daratumumab (Darzalex), which attaches to a protein called CD38 that is present on plasma cells (the white blood cells that become cancerous in myeloma). By sticking to myeloma cells, monoclonal antibodies help the immune system fight the cancer. Daratumumab was a breakthrough that led to more success in the treatment of multiple myeloma.

Researchers have also developed a newer version of this drug called daratumumab hyaluronidase-fihj (Darzalex Faspro). Although daratumumab is typically given intravenously (through an IV infusion), daratumumab hyaluronidase-fihj treatments are simply injected under the skin (subcutaneously) and thus administered much faster.

The U.S. Food and Drug Administration (FDA) initially approved daratumumab hyaluronidase-fihj in May 2020 for adults with multiple myeloma. People with new diagnoses can use this medication along with other drugs. Daratumumab hyaluronidase-fihj can also be used on its own in the treatment of relapsed or refractory myeloma.

Clinical trials show that this drug is a promising treatment option. When taken along with the medications dexamethasone and lenalidomide, daratumumab hyaluronidase-fihj led to improvements for about 9 in 10 people with myeloma who had already tried at least one other medication.

Researchers are working to develop other anti-CD38 monoclonal antibodies. Some studies are also investigating whether drugs that target other molecules found on plasma cells may help treat myeloma. Clinical trials of these medications may be a good way for people with myeloma to access other potential treatment options.

New Treatment Regimens With Monoclonal Antibodies

In addition to studying potential new drugs, researchers are looking into the effectiveness of combining different medications. Some new combinations have been approved in the past couple of years, further expanding treatment options for people with relapsed or refractory multiple myeloma.

Recently approved treatment regimens include:

  • Daratumumab hyaluronidase-fihj in combination with the immunomodulatory drug pomalidomide (Pomalyst) and the corticosteroid dexamethasone for people with myeloma who have already tried at least one other treatment
  • Daratumumab, dexamethasone, and lenalidomide, an immunomodulating agent (a substance that helps the immune system fight disease), for those who have been recently diagnosed with myeloma and can’t receive an autologous bone marrow transplant
  • The monoclonal antibody isatuximab-irfc (Sarclisa) along with pomalidomide and dexamethasone for people with RRMM who had prior treatment with two or more other medications
  • Isatuximab-irfc plus dexamethasone and the proteasome inhibitor carfilzomib (Kyprolis) for those with RRMM who have tried between one and three previous treatments

Read more about relapsed/refractory myeloma.

Antibody-Drug Conjugates

Antibody-drug conjugates consist of a monoclonal antibody attached to a chemotherapy drug. The monoclonal antibody helps bring the cell-killing chemotherapy in contact with cancer cells.

The FDA approved a medication in this category — belantamab mafodotin (Blenrep) — in August 2020. This medication targets a protein called B-cell maturation antigen (BCMA), found on myeloma cells.

Belantamab mafodotin can be used to treat people with RRMM after they have tried four or more other types of treatments. In a clinical trial, this drug helped reduce the amount of cancer in the body for almost one-third of study participants.

Other Targeted Therapy Drugs

Targeted therapies block specific molecules found on cancer cells to kill or prevent the cells from growing. Monoclonal antibodies and related medications are types of targeted therapy, but there are other types as well.

The targeted therapy drug Xpovio (Selinexor) is a type of nuclear export inhibitor — it blocks a molecule that helps carry proteins around the cell. Without this essential protein, myeloma cells can’t survive. Xpovio was approved in December 2020 for people with RRMM after studies showed that it could help people avoid relapses for longer periods.

Chimeric Antigen Receptor T-Cell Therapy

A newer type of immunotherapy, chimeric antigen receptor (CAR) T-cell therapy, helps genetically engineer the immune system to better fight cancer. During this treatment, some of a person’s T cells — immune cells with destructive capabilities — are removed. The genes within these cells are then changed so that they can better recognize myeloma cells. The T cells are then delivered back into the body, where they can activate the immune system to fight against myeloma cells.

So far, two CAR T-cell therapies have been FDA approved to treat myeloma — idecabtagene vicleucel (Abecma) — also called ide-cel — was approved in 2021, and ciltacabtagene autoleucel (Carvykti) received approval in 2022. Both therapies, which train the immune system to attack the BCMA protein, can help treat people with RRMM.

Research found that ide-cel helped improve myeloma for 73 percent of people. It also helped people avoid relapses or early death. Additionally, ciltacabtagene autoleucel led to improvements for nearly 98 percent of study participants.

Additional clinical trials continue to look for new CAR T-cell options. For example, studies are underway to develop a therapy that would target other proteins on myeloma cells, such as GPRC5D.

Bispecific Antibodies

Bispecific antibodies are medications that help the body’s immune system more effectively attack cancer. Most antibodies recognize just one type of protein, but bispecific antibodies can target two of them: One part attaches to a protein on a myeloma cell, and the other part attaches to a protein on a T cell. This brings immune cells and cancer cells together to help the immune system destroy the myeloma.

No bispecific antibodies are currently approved to treat multiple myeloma, but a few are under development. One promising new option is teclistamab, which targets myeloma cells through the BCMA protein and helps activate T cells to kill the cancer.

In clinical studies, teclistamab helped shrink myeloma in nearly two-thirds of people with RRMM. Additionally, 40 percent of participants experienced complete remission — they had no remaining signs of myeloma after using this drug.

Teclistamab is still under research, and the FDA is evaluating whether to approve it. Other clinical studies are also analyzing the safety and effectiveness of bispecific antibodies that block other proteins found on plasma cells.

Are You Eligible for New Treatment Options?

If you’re curious whether you may be eligible for any newly approved treatment options, talk to your oncology specialist. You may also be eligible to participate in clinical studies researching promising new therapies. Your health care team can help you identify all of your options.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 16,000 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

Would you like to know more about new treatments for relapsed or refractory multiple myeloma? Have you discussed possible options with your health care provider? Share your thoughts in the comments below, or start a conversation by posting on your Activities page.

References
  1. Relative Survival for Multiple Myeloma — Multiple Myeloma Research Foundation
  2. Cancer Stat Facts: Myeloma — National Cancer Institute Surveillance, Epidemiology, and End Results Program
  3. Relapse — National Cancer Institute
  4. Refractory Cancer — National Cancer Institute
  5. Monoclonal Antibody Drugs for Cancer: How They Work — Mayo Clinic
  6. Drug Therapy for Multiple Myeloma — American Cancer Society
  7. Multiple Myeloma: Improved Prognosis With the Latest Treatments — Memorial Sloan Kettering Cancer Center
  8. Multiple Myeloma: Types of Treatment — Cancer.Net
  9. FDA Approves Daratumumab and Hyaluronidase-fihj for Multiple Myeloma — U.S. Food and Drug Administration
  10. Immunotherapy in Multiple Myeloma — Cancer Treatment and Research Communications
  11. FDA Approves Daratumumab and Hyaluronidase-fihj With Pomalidomide and Dexamethasone for Multiple Myeloma — U.S. Food and Drug Administration
  12. FDA Approves Daratumumab for Patients With Transplant-Ineligible Myeloma — ASH Clinical News
  13. FDA Approves Isatuximab-irfc for Multiple Myeloma — U.S. Food and Drug Administration
  14. FDA Granted Accelerated Approval to Belantamab Mafodotin-blmf for Multiple Myeloma — U.S. Food and Drug Administration
  15. Belantamab Mafodotin for Relapsed or Refractory Multiple Myeloma (DREAMM-2): A Two-Arm, Randomised, Open-Label, Phase 2 Study — The Lancet Oncology
  16. FDA Approves Selinexor for Refractory or Relapsed Multiple Myeloma — U.S. Food and Drug Administration
  17. CAR T-Cell Therapy for Multiple Myeloma — American Cancer Society
  18. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma — The New England Journal of Medicine
  19. FDA Approves Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma — U.S. Food and Drug Administration
  20. Teclistamab in Relapsed or Refractory Multiple Myeloma — The New England Journal of Medicine
  21. Complete Remission — National Cancer Institute
  22. Bispecific Antibodies in Multiple Myeloma: Present and Future — Blood Cancer Discovery
Posted on December 13, 2022
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Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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