Refractory multiple myeloma refers to a form of the disease that no longer responds to standard treatments.

In some cases, patients experience a relapse after achieving remission (relapsed myeloma), while others may develop resistance during or after therapy. Treating refractory myeloma can be challenging, but recent advances in research and therapy have opened the door to new and more effective options.

Why Does Myeloma Become Refractory?

Multiple myeloma becomes refractory when cancer cells adapt to treatments and continue to grow despite therapy. Resistance may develop to:



  • Proteasome inhibitors (e.g., bortezomib, carfilzomib)




  • Immunomodulatory drugs (e.g., lenalidomide, pomalidomide)




  • Monoclonal antibodies (e.g., daratumumab, elotuzumab)



Patients may become double-refractory (resistant to two drug classes) or triple-class refractory, which means their disease resists all three major classes. This often requires a more aggressive or innovative treatment approach.

Standard Options for Refractory Myeloma

When myeloma relapses or becomes refractory, doctors typically switch therapies or combine different agents for a synergistic effect. Common strategies include:



  • Changing drug classes: Switching to a drug from a different class can help overcome resistance.




  • Combining therapies: Multi-drug regimens can enhance efficacy and delay further resistance.




  • Using higher-generation agents: Newer versions of existing drugs may work where others failed.



Some of the most used regimens include:



  • Carfilzomib + dexamethasone ± other agents




  • Pomalidomide + dexamethasone + monoclonal antibody




  • Selinexor + bortezomib + dexamethasone (for patients with previous drug exposure)



Emerging Treatments for Refractory Myeloma

Patients who have exhausted standard options may be eligible for newer treatments, including:



  1. CAR T-Cell Therapy

    Chimeric Antigen Receptor (CAR) T-cell therapy is a personalized treatment that modifies a patient’s T-cells to target and destroy myeloma cells.



    • FDA-approved therapies include idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti)




    • Shows strong response rates even in heavily pre-treated patients






  2. Bispecific Antibodies

    These therapies engage both the myeloma cell and the immune system simultaneously, bringing immune cells directly to the cancer.



    • Examples include teclistamab and elranatamab




    • Administered via injection or infusion and showing promising outcomes in clinical trials






  3. Antibody-Drug Conjugates (ADCs)



    • Belantamab mafodotin was one of the first ADCs approved for myeloma, targeting BCMA on myeloma cells




    • Delivers chemotherapy directly to cancer cells while sparing healthy tissue






  4. Novel Oral Therapies



    • Selinexor is a selective inhibitor of nuclear export (SINE) and offers a new mechanism of action for resistant disease




    • Often combined with other agents for better results





Clinical Trials: Access to Tomorrow’s Treatments Today

Patients with refractory myeloma may benefit from enrolling in clinical trials, which provide access to promising new therapies before they are widely available. Trials may involve:



  • New combinations of existing drugs




  • First-in-class experimental treatments




  • Therapies tailored to genetic mutations or biomarkers



Your healthcare provider or cancer center can help determine eligibility and locate appropriate trials.

Supportive Care and Quality of Life

Refractory myeloma requires ongoing care to manage symptoms and maintain quality of life. Supportive care measures include:



  • Bone-strengthening agents to prevent fractures




  • Pain management plans




  • Nutritional counseling




  • Emotional and mental health support



An integrated care team — including oncologists, palliative care specialists, and support services — ensures that patients remain as comfortable and functional as possible.

When to Consider a Stem Cell Transplant Again

For some patients, a second autologous stem cell transplant (ASCT) may be an option, particularly if the first transplant provided a durable response. This is generally considered for younger, fit patients and requires careful evaluation by a transplant specialist.

Conclusion

While refractory multiple myeloma poses serious challenges, treatment options continue to expand rapidly. From advanced drug combinations to revolutionary therapies like CAR T-cells and bispecific antibodies, patients now have access to more hope than ever before. Working closely with a knowledgeable oncology team and exploring clinical trials can help patients with refractory myeloma find effective treatment pathways and improved outcomes.

If you or a loved one is facing treatment-resistant myeloma, don’t lose hope. New options are emerging every year, and staying informed is the first step toward taking control of your care.