EHA 2023 | Multimodal prediction of survival in myeloma: combining MRD testing with MALDI-TOF MS & imaging

With multiple myeloma, we have a plethora of new agents that are coming through, but the delivery of these treatments is based on having good diagnostic agents and monitoring agents, and so what I’ve been talking about is the role of MRD testing and blood-based techniques as well as cross-sectional imaging.

Well we know that achieving complete remission is not a good enough biomarker in terms of survival, and we need better surrogate markers to predict for patient’s overall survival. Typically, in a clinical trial we will look at progression-free survival, but for some of our patients, progression-free survival can be a number of years – so for a frontline study, we’re expecting a progression free survival of five years, which is quite a long time to wait to know if your patient is doing well. And given that complete remission isn’t good enough, then we need to be looking for other markers. Now, minimal residual disease is a technique that has been looked at in a number of different clinical trials and there was a recent meta-analysis performed by Dr. Munshi. He looked at thousands of patients, both newly-diagnosed and relapsed and showed a strong correlation between achieving MRD negativity, PFS benefit and overall survival benefit. And to me, that provides the link of surrogacy in terms of MRD and those later end points. However, what we do know is that MRD’s a continuous spectrum. 10^-5 level of attainment is what’s recommended in terms of the IMWG, but for ultra-high-risk patients, which are that patients with two or more high-risk features, we need to be achieving 10^-6 at least, because what we know from the MASTER study is if you stop treating those patients, they relapse.

Now MRD has its problems: we know that there are problems with sampling, and we also know that it’s a painful procedure that patients do not like to have, and the third aspect is that there is heterogeneity of the disease with extra medullary disease, which may not reflect the bone marrow sampling. And that’s where blood-based techniques can be very important, and the MALDI-TOF method of mass spectroscopy is interesting in terms of looking at the overall burden of disease. But however, what we’ve discovered is that mass spec does not replace bone marrow-based MRD testing – it’s not sensitive enough – but it provides more complementary information.

And then finally, because of the heterogeneity of the disease, it’s important to perform whole body functional imaging. And there’s very good data from the French IFM studies, which shows the prognostic impact of FDG-PET, showing that those patients who are negative have better outcomes. But on top of that, if you are FDG-negative and also MRD-negative in the bone marrow, then that gives you the most superior survival outcomes.

And so when you put this all together, what we’re coming to at this stage is having multimodal testing. What we need is blood-based techniques with immunofixation, we need mass spectrometry to be for improvement in immunofixation testing, and we need bone marrow-based MRD testing coupled with whole body cross-sectional imaging. And if you do that, then you will understand your patient better. And I think you can personalize some of these novel therapies better.