The ‘gold standard’ of first-line treatment in multiple myeloma – is it time for a rethink?
This article originally appeared on Linkedin on 19 March 2022.
Actions speak louder than words.
For the multiple myeloma (MM) community, these words ring true with every treatment breakthrough that is made: they are actions that bring new hope as we work towards a cure.
The same words also underpin this year's Myeloma Action Month (MAM), which is the same month that EBMT’s 48th Annual Meeting takes place. These make March a key moment to look at how we must continue to push the boundaries of science, to go beyond our words and deliver on our promise to improve the lives of people living with MM.
And lives are improving: there has been great progress already in treatment advances in MM, and I’m proud to work for a company whose work has been part of this progress – and who are still helping to shape the future of tailored treatments in haematology.
As a community, we have gone from the development of a first-in-class proteasome inhibitor treatment some twenty years ago, to now exploring the ground-breaking reaches of personalised medicine through CAR-T therapy and beyond.
Yet, despite these advances, MM remains the second most common form of blood cancer and we are yet to discover a cure. So it is important to think about how we could further optimise our approach – by thinking about where we are now, and where we want to get to in the future.
The 'gold standard": What is the current recommended treatment for newly diasnosed multiple myeloma?
In Europe, the two main factors that drive the treatment approach for newly diagnosed MM patients are:
- their eligibility for high dose therapy (HDT) and autologous stem cell transplantation (ASCT), a process where healthy blood stem cells from a person’s body are used to replace their damaged bone marrow
- risk factors, such as age and fitness
If these MM patients meet the eligibility criteria for HDT and ASCT, then this first-line treatment is the current go-to approach, and undeniably a valuable, life-extending one. Progression-free survival for people who have received an HDT-ASCT combination therapy is around 3.5 years.
That said, this overall survival is not a guarantee, and the toxicities of this combination of treatments can also impact a person’s quality of life, and sometimes even limit life expectancy., For me, this raises questions around whether it is the only ‘gold standard’ front-line therapy, particularly as some patients are ineligible, or whether we should look to other options too.
Is HDT-ASCT the only option in the frontline for multiple myeloma treatment?
In our haematology team at Janssen, we are looking at how we can not only extend people’s lives but also improve the quality of life for people living with blood cancer.
As such, with the approval of many novel therapies with less toxicity, there is growing consensus that HDT-ASCT may not always be the best initial treatment option for eligible patients newly diagnosed with MM.
What’s more, exciting advances in technology allow us to better detect minimal residual disease (MRD) – the re-emergence of very low levels of cancer cells for patients in complete remission – with a high degree of sensitivity (≤10−5).
These residual cells are important prognostic biomarkers that help us to understand the likelihood of disease progression and relapse. A person who tests “MRD negative” following treatment for MM has less than one myeloma cell per million bone marrow cells. This is important because newer therapies can achieve deeper responses, which are inadequately captured by traditional response criteria alone.
Achieving a deeper response rate with newer therapies in MM is vital because the deeper the response, the longer remission is likely to be sustained.
So what is the optimal first-line treatment?
As the medical community moves away from conventional ‘one-size-fits-all’ approaches to treatment, MM care is no exception. We must tailor treatment options to the needs of each individual, finding specific or combination therapies that work for them and their cancer. There might not be a single gold standard that everyone turns to.
For example, the introduction of monoclonal antibodies earlier has been shown to increase the chances of obtaining durable responses, with many patients achieving MRD negativity. We are also witnessing triplet induction regimens resulting in deeper responses than doublet regimens. And we can take this further still – results achieved by newer quadruplet therapies are showing even greater potential.
The more options available, the more chances we will have to find winning combinations that improve overall survival with fewer toxicities for patients. These newer regimens will likely become a cornerstone of frontline therapy options for newly diagnosed younger patients.
Of course, HDT-ASCT will remain an important option for many people, bringing them significant benefits. However, with novel combination regimens that provide lasting remissions, coupled with extremely sensitive MRD detection, I believe we are entering an era where the HDT-ASCT approach will go from a requirement to an option, shifting the status quo for front-line therapies.
Committing to further action
Every day I see actions at Janssen that lay the groundwork for further advances with the potential to improve not only the outcomes of people living with MM, but also their treatment experience.
EBMT will provide us with an inspiring opportunity to hear about the actions of others in our industry, as well as physicians, patients and more. And we can take these into the rest of MAM, reaffirming our commitment to change what it means to receive a MM diagnosis and one day find a cure.
That is the ultimate purpose of our actions in MM – this month, what actions are you taking to help us get there?
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