Frontline Therapy Advances for Multiple Myeloma Patients | ASH 2024 Insights for Patients 

Dr. Joseph Mikhael

In my overview video of the American Society of Hematology Annual Meeting, I identified five key areas of research in multiple myeloma. Let's dive into area number two, frontline therapy. To learn more about the other areas that we're exploring from ASH, please subscribe to our YouTube channel and you can learn about the other four areas that I highlight.

We know that what we do as first line or frontline therapy for multiple myeloma patients has a really important impact down the line on the time and remission, and indeed, their overall survival. There has been a strong trend over the last couple of years of moving from three drug combinations to four drug combinations or quadruplets. At ASH this year, we learned a lot more about these quadruplets.

Interestingly, we saw them both in patients who are eligible or going to a stem cell transplant, as well as those that are not going to transplant. And what we're learning is that we get patients into a deeper and a more durable response. The German GMMG study demonstrated to us that two-thirds of patients with a quadruplet therapy of isatuximab, bortezomib, lenalidomide, and dexamethasone and a single autologous stem cell transplant can achieve MRD negativity or minimal residual disease negativity in two-thirds of patients.

These are the kinds of numbers that we've not seen before. But not only does it provide a depth of response, it provides a duration or a durable response where that lasts for a very long period of time. And so with this study, with the IMRAS study, with the CEPHEUS study, with the PERSEUS study, these maybe funny words to you, but these are all large clinical trials that compared four drugs to three drugs.

We're seeing a consistent trend of the benefit of quadruplets over triplets. But before I close off, before we think that it's all about more is better, we also, ironically, had a study that demonstrated that in some situations, less is more. And that comes to the fourth drug that we use in these combinations, dexamethasone. Dexamethasone is the drug that we kind of love and hate.

We love it because it boosts the effect of other drugs, but we kind of hate it because as people stay on it, it causes a lot of side effects and it could affect people's sleep and blood pressure and blood sugar and all sorts of other things. One of the French trials presented giving dexamethasone for only two months at the start of someone's treatment and then discontinuing it.

And I think this speaks to the importance of what I call the Down with Dex movement, where we realize that Dex can be very helpful at first, but then we can dial it down in the dose and even discontinue it. And we hope that this will now be implemented in other clinical trials as we go forward. So great things are happening in multiple myeloma and in particular in frontline therapy.