Unlocking the power of the immune system: Professor Graham Jackson discusses pioneering myeloma treatments

In December, ASH2023, the world’s largest haematology conference, brought together specialists from all over the globe to discuss a huge range of myeloma topics and breakthroughs in cutting-edge myeloma research.

Across our social media you told us that you were most excited to hear about updates to new treatments. At ASH, immunotherapies took centre stage as the most exciting area of focus for emerging myeloma treatments.

Professor Graham Jackson, consultant haematologist and Myeloma UK’s Chief Clinical and Scientific Advisor, describes how immunotherapy fits into today’s (and tomorrow’s) treatment landscape.

The emergence of immunotherapy for myeloma

As a clinician, immunotherapy is one of the most exciting areas of developments I’ve seen in recent years, so it’s great to see that this was high on the agenda at ASH. Immunotherapy describes a group of treatments which harness the patient’s immune system to kill myeloma cells. Over the last 15 years, these developing treatments have become increasingly important and effective in the pursuit of longer remissions – something we all want to see.

Immunomodulatory agents (IMiDs) like lenalidomide (Revlimid®) have shown us that the immune system can be harnessed to suppress myeloma. Since then, monoclonal antibodies such as daratumumab (Darzalex®) and isatuximab (Sarclisa®) have added to the repertoire of available treatments which engage the body’s own immune system to target myeloma cells.

Unfortunately, we have also learnt that myeloma is able to suppress the immune system. This is one of the reasons why people with myeloma are more at risk of infections. This myeloma induced immunosuppression also makes treatment complicated because it impacts how effective the immune system, and the treatments which harness its power, can be in tackling myeloma.

The role of CAR-T cell treatment

Researchers, determined to overcome this problem, developed CAR-T cell (Chimeric Antigen Receptor-T cell) treatment. These groundbreaking CAR-T cell treatments work by crucially modifying the patient’s own T-cells cells – a type of white blood cell of the immune system which can both kill abnormal and/or harmful cells like myeloma cells, and recruit other immune cells to destroy the target.

This treatment is highly personalised, involving genetic modification of each patient’s own T cells – read more about how they work in our CAR-T cell treatments Infosheet. This individualised approach is difficult and costly to mass produce, although it is hoped this may improve as the technology continues to develop.

Though CAR-T cell treatment is promising and exciting, it does have side effects. People often become more vulnerable to infections. Cytokine release syndrome (CRS), a flu-like illness, can affect many myeloma patients following CAR-T cell treatment and for some, may be serious. Some people can experience confusion and movement problems caused by immune effector cell-associated neurotoxicity syndrome (ICANS) and this complication can vary from mild to severe.

As a result it is not unusual to be hospitalised for two to four weeks, occasionally requiring intensive care for short periods. However, despite these difficulties CAR-T cell treatments achieve remarkable outcomes, with some clinical trials reporting responses in over 90% of patients, many experiencing very deep remissions.

Beyond CAR-T cell treatment: evolving options

I have no doubt that CAR-T cell treatments are an exciting prospect for the future, but for now, access in the UK is limited. However, immunotherapy remains an encouraging area of focus because there are other new drugs available, and more emerging treatments in development:

  • Monoclonal antibodies – in addition to daratumumab and isatuximab, other monoclonal antibodies continue to be developed, ensuring more options for different groups of patients, for longer
  • Bispecific antibodies (sometimes known as T cell engagers) – there are a number of bispecific antibodies at different stages of development at the moment, offering more variety and showing great promise in improving remissions for myeloma patients
  • CELMoDs (cereblon E3 ligase modulatory drugs) – these work in a similar way to immunomodulatory drugs (IMiD’s) like lenalidomide, but often are still effective even when the patient has resistance to IMiD’s. At ASH, we heard about a clinical trial researching an exciting CELMoD, iberdomide, that looks set to enhance patient outcomes when used as a maintenance treatment following high-dose therapy and stem cell transplantation (HDT-SCT)
  • Antibody-drug conjugates – some immunotherapy treatments offer precision delivery of powerful chemotherapy drugs, usually too toxic to be given alone, directly to myeloma cells. These treatments, like belantamab mafodotin (Blenrep®), combine monoclonal antibodies with a chemotherapy drug to help guide the chemotherapy straight to the myeloma cells

Read more about these different treatments in our Immunotherapy in myeloma Infosheet.

It’s incredible to see the progress being made, with current research exploring even more novel immunotherapies, as well as new ways of combining existing treatments for improved patient results.

Future directions

There are still challenges; a need for more research to understand how to optimise treatment, reduce side effects and to learn how to overcome treatment resistance. But this variety of immunotherapy treatments presents exciting prospects for the future of treating myeloma – and for patients.

Not only are immunotherapies offering excellent outcomes for people in the form of deep and long-lasting remissions – but they are also offering more choice, for longer. In clinical trials, some novel treatments have even indicated impressive responses for patients after several previous treatments.

As we learn more about how the immune system interacts with myeloma, we can hone our treatments even more, maximising the impact of the patient’s own defenses and minimising short- and long-term side effects. One day we hope to eradicate multiple myeloma and find a cure.

Close-up photograph of a hand holding a mobile phone.

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