• Multiple Myeloma News
    • Oct 07, 2019

    A Reason Why Myeloma Patients Might Become Resistant to Bortezomib


Israeli researchers identified why multiple myeloma may become resistant to Velcade (bortezomib) by studying the complex signaling that happens in the bone marrow environment. Velcade is a proteasome inhibitor and is a standard treatment for the disease. Velcade is used for induction therapy, in combination therapies and also as maintenance therapy. Although it prolongs survival, some patients can become resistant to Velcade over time. 

Testing Velcade on human myeloma cells in the lab and in mice, the researchers found that Velcade promotes the enrichment of cancer stem cells called tumor initiating cells. Even a small number of these precursor cells can initiate myeloma growth. Velcade helps a type of white blood cells called macrophages grow. These macrophages cause an inflammatory response and secrete an inflammatory protein called Interleukin-1 beta (IL-1β) that encourages these tumor initiating cells to grow. 

This is a common occurrence. Other types of anti-cancer drugs including chemotherapy, radiation and other targeted drugs can generate these types of responses that counteract the anti-tumor activity of the drugs and this is what typically drives drug resistance and relapse. 

Velcade-treated mice had almost a 40% increase of these pro-inflammatory macrophages compared to myeloma mice untreated with Velcade. According to the researchers: 

“We demonstrate that pro-inflammatory macrophages secrete IL-1β, which in turn contributes to tumor initiating cell (TIC) enrichment. Clinically, the levels of pro-inflammatory macrophages in patients treated with bortezomib correlates with worse outcome. Our results therefore suggest that characterization and enumeration of pro-inflammatory macrophages in the bone marrow may serve as a prognostic factor for multiple myeloma progression following bortezomib therapy.”

Testing for these macrophages with a bone marrow biopsy following Velcade treatment could help explain why some patients’ myeloma becomes resistant to Velcade and could indicate which patients are more likely to develop resistance. When they tested bone marrow samples of myeloma patients who received bortezomib, they found that an increased level of IL-1β contributed to myeloma tumor initiating cell enrichment and may serve as an indication of an aggressive disease.

Early clinical trials are now testing how to block these pro-inflammatory IL-1β cytokines. In multiple myeloma, a new drug called Anakinra is being used in a clinical trial to reduce mucositis during stem cell transplant. This is an IL-1β inhibitor that has been FDA approved for the treatment of rheumatoid arthritis. 

Another study is using the same Anakinra drug with lenalidomide and dex in early myeloma to see if it can prevent the disease from growing. 

The researchers conclude with the idea that testing these macrophage and tumor initiating cell levels in the bone marrow before and after treatment could be added to current testing to help predict who might become resistant to drugs such as bortezomib. 

“At present, with the wide repertoire of treatment options for MM patients, it is imperative to incorporate biomarkers that would preclude one treatment modality over the other in clinical decision making,”

About Author

Jenny A

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical trials. Founder of Myeloma Crowd, Myeloma Crowd Radio and the CrowdCare Foundation.


  1. Carey kennard October 9, 2019 at 1:34 pm

    Are there clinical trials available for patients living in south Africa

    • Jenny A
      Jenny A October 10, 2019 at 11:04 am

      Carey, I don’t know of any myeloma trials for patients in South Africa, sorry.

  2. Ray October 9, 2019 at 2:16 pm

    My wife is in remission now after the stem cell transplant 3 years ago. Doctors prescribe her Revlimid every 14 days cycle. So many side effects on her though.

    • Jenny A
      Jenny A October 10, 2019 at 11:05 am

      Ray, always tell your doctor about her side effects because they can modify her dose if needed!

  3. Sharon October 9, 2019 at 4:06 pm

    I wonder if you could provide an option to print these articles without having to print the entire web page?

    • Jenny A
      Jenny A October 10, 2019 at 11:04 am

      Sharon, we just added this feature just for you! Check it out!

  4. Laura Bloomfield October 9, 2019 at 10:07 pm

    Very interesting. Just found out today my myeloma is back after about 1 year from tandem sit transpants and Maintence chemo. Was in complete stringent remission. Was in remission before transplant. Have been on velcade since diagnosis in Feb 2018. Also dex and cytoxan prior to transplant..Thalidamide between transplants. Maintence was weekly velcade nd dex and revlimid. First change in bloodwork was still on revlimid and now on cytoxan velcade dex. New protocol starting is pomalyst krypolis and dex.

    • Jenny A
      Jenny A October 10, 2019 at 11:03 am

      Laura, sorry to hear you have relapsed, especially so soon after tandem transplants. This disease is very tricky. I hope you are with a myeloma expert. If you have questions or need help, you can always email me at info@crowdcare.org.

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