International study led by UCalgary explores why multiple myeloma patients often relapse after immunotherapy

Understanding how tumour cells build resistance to treatment may impact future individualised cancer care

Multiple myeloma is the second most common blood cancer in adults.

It starts in the white blood cells that are responsible for creating antibodies that help the body fight infections.

Once the myeloma cells begin to multiply, it makes it harder for the blood cells to function properly.

There are effective treatments for multiple myeloma, including immunotherapies that can significantly extend survival, however, in some, the cancer cells become treatment resistant.

A University of Calgary study led by members of the Arnie Charbonneau Cancer Institute, published in Nature Medicine, takes a closer look at why patients often relapse after immunotherapy by studying how the myeloma cells adapt to treatment.

By understanding how the cancer builds resistance, future treatments can be designed to take this into account with the goal of preventing another relapse.

“Multiple myeloma tumour cells are highly adaptable under therapeutic pressure,” says Dr. Holly Lee, MD, PhD, a clinical assistant professor at the Cumming School of Medicine and first author on the study.

“A treatment could be incredibly effective, bringing disease bulk down from about 100 per cent to about one to two per cent but all it took was that one to two per cent of the cells that were left to adapt and cause this relapse in patients.”

Gaining an understanding to create better treatments

Lee alongside project leads, Drs.Paola Neri, MD, PhD, and Nizar Bahlis, MD, assessed data gathered from clinics across North America, Europe, and Asia.

They looked at the tumour cells of patients who relapsed after having gone through a form of immunotherapy called bispecific T-cell engager so they could better understand why the cancer was becoming resistant to treatment over time.

This therapy helps the immune system identify and attack the multiple myeloma cancer cells by targeting a protein on the tumour cell called GPRC5D.

The protein sits on the surface of the myeloma cell.

They found that the tumour cells adapted in multiple ways.

Lee says understanding these different adaptations can guide the development of next-generation treatments, designed to anticipate and overcome these changes.

“Immunotherapy is quite an active topic when it comes to myeloma research because it’s really changing how we practice in our clinics and what we’re able to offer to patients,” says Lee.

“For us to really cure myeloma, we have to understand the tumour cells and develop treatments to stay ahead of them building that resistance.”

Researchers also found that it is quite common for the tumour cell to go through some form of protein mutation.

About 60-70 per cent of relapsed patients studied relapsed because of the myeloma cell protein adapting.

Study contributes to a larger picture: personalised, individual cancer therapy

The research highlights that treatment can not be a one-size-fits-all approach.

Researchers add the findings don’t just relate to multiple myeloma, but to all cancers.

“Cancer is not one disease,” says Lee, “each cancer and each patient behave very, very differently. We have patients who are in remission for four or five years and others who relapse within six months after receiving the same therapy. I think this paper and this study is a step towards personalised cancer therapy.”

The goal moving forward is to implement more targeted screening within clinical practices with a quicker turn around time to better support the treatment process for patients in real time.

Source: University of Calgary