EHA 2025 | Ask the Expert: Rakesh Popat answers your questions on multiple myeloma at EHA 2025

Hi, my name is Rakesh Popat and I’m a hematologist based at University College Hospital in London in the UK. I’m here at EHA 2025 in Milan and with the VJHemOnc team doing Ask the Expert. Thank you guys so much for sending in your questions. Got some really interesting topics to discuss. Not sure I know all the answers but they’re certainly really pertinent questions for a conversation. So let’s kick off with the first question. This is from Mustafa, clinical director at MedStar. Thank you so much for this question. What would be your treatment for a solitary plasma cytoma patient who has residual metabolic activity after radiation therapy? Now this is a really, really interesting and clinically relevant question because we do see this quite often in this situation. So let me just backtrack a little bit and put a bit of background in. The management for a patient with solitary plasma cytoma is with radical radiotherapy and we anticipate that a good proportion of these patients will be cured. Now having said that we do need to monitor these patients clearly following the radiation therapy looking out for relapse. Typically when the relapse occurs it is actually often not at that site that was irradiated because the radiation field is quite broad and secondly the radical dose of radiotherapy is very high and extensive. So actually when people relapse following the solitary plasma cytoma it is in a different part of the skeleton. So in terms of how you manage these patients you do need to be monitoring with whole body imaging modalities. You can take your pick whether you do CT PET scans or whole body MRI. For extramedullary plasma cytomas the modality of choice would indeed be CT PET. But what I’m directly answering your question is that you need to be very careful with acting on a scan that has residual FDG activity, particularly early on following radical radiotherapy, because it can take months and sometimes over a year for it to resolve. So the first point is if you do see residual FDG activity, I would continue to monitor. I’ll continue to monitor and you do regular scans and then you see where things are following 12 months. If you still have residual activity over 12 months, I would continue to perform active surveillance. There is no indication to commence systemic treatment simply because of residual activity. The reason to start systemic treatment is if the patient then goes on and develops the features of myeloma, i.e. they develop either SLIM or CRAB criteria and what you need to be doing at that point is monitoring very closely both in terms of blood urine and whole body MRI assessments. So I hope that answers your question Mustafa, super interesting question.

We’ll move on to question number two. This is from Mariel Fragna Salimbi who is based in Brazil. So fantastic question from Brazil. When could patients with multiple myeloma after initial treatment potentially practice physical activities like soccer? Thank you so much for your question. This is a question that patients ask us day in day out of clinic. It’s such a relevant question for the myeloma community. Alright so to answer your question it’s not straightforward is the answer. What you need to do is to assess the bone structural elements of the patient. So typically you would do a whole body CT scan either you do a whole body low-dose CT maybe that’s what you in Brazil or you might do a whole body PET CT scan. The reason why the CT component is very important here is because it assesses the structural integrity of the bone and it’s far better than an MRI in this setting. So what you need to do is that you have your baseline CT scan and then you perform a follow-up scan after you’ve finished treatment and then that will guide you as to what level of physical activity that the patient can do. It is most likely that a patient could do something like soccer because soccer is more of a low impact activity. What you worry about more is, particularly with people with spinal disease, is twisting movements. So for example golf is a problem because of the twisting of the spine that happens and other high impact activities such as contact sports, maybe rugby, maybe American football, maybe things like bungee jumping, abseiling, which are more kind of high impact activities. You need to be a little bit more careful. Cycling, for example, is normally something that you could do, but you might want to be a little bit careful and slowly build that up. My recommendation is that you have input from either your orthopedic team or your spinal team to guide in terms of the absolute answer. And then the final point is about physiotherapy. So for these patients, and I’m assuming that this is presumably a younger and more active patient who wants to return to soccer, physiotherapy input early on is incredibly important to allow that patient to return to physical activity. Because what we do know is that physical activity is good in terms of the long-term survival of the patients. So again, thank you for that very relevant question.

I’m now going to move over to Turkey and Meral Becsak, thank you so much for sending this question in from Ankara University. In your daily practice, do you defer autologous stem cell transplant for newly diagnosed myeloma patients? And if yes, how do you decide? Meral, this is a spot-on question and right on exactly what we’re discussing currently day in, day out for myeloma patients. In my personal practice, I do not defer autologous stem cell transplants. In the UK, we offer a stem cell transplant for all younger, fitter patients and we would not defer those patients. However, there are a small proportion of patients who do not wish to proceed to a transplant because they do not want to undergo the toxicity for that. And so I think in those cases, it would be reasonable to do that as long as you have stem cells stored. But perhaps answering your question more broadly, the question relates to what data we have so far. All the data that we have, both from the UK Cardamon study, the IFM study, and more recently the Dana-Farber study called Determination. All of those data suggest that stem cell transplantation continues to remain superior according to standard treatment. The only study that was just reported at ASCO that puts this into doubt is the MIDAS study. And the MIDAS study, as you know, used isotuximab KRD, which is not standard treatment, and they had very high levels of MRD negativity. And I think what that shows you is that if you were MRD negative following induction treatment, that may be the one group of patients who you could stop treatment. So I think if you were MRD negative post-induction and if you were standard risk, that would be the one group of patients who I would defer transplant to. So again, thank you so much for that question.

And Meral, you’ve asked another question. Fantastic. How do you decide to stop maintenance therapy? Again, this is such a hot topic. And I assume, Meral, that you’re talking about lenalidomide maintenance following autologous stem cell transplants in terms of that question. So again, the clear answer is we don’t know because we don’t have prospective studies to give this answer. But there is some very interesting retrospective data to that. The first piece of real-world evidence I would put forward is that we know in terms of real-world evidence that patients will naturally stop lenalidomide maintenance around two to three year mark, normally because of intolerance. So that’s typically what we’re seeing. But what does the clinical trial data show? Well, my colleague Charlotte Pawlyn from the UK did some retrospective analysis from myeloma 11 and what we looked at was to look at the benefits of ongoing treatment at one year, two years, three years, four years, five years and six years. Now of course there is some bias built into that because it’s to do with how well patients are responding. But what she suggested was that once you hit the three-year plus mark, the added benefits of ongoing lenalidomide maintenance is marginal. And so I think if you’re going to stop treatment, And if you’re in CR, potentially MRD negative at three years, that would be the time to think about stopping. There is some collaborative data from the Greek group who did a prospective study, and that shows very similar data. So I would put to you around about the three or four year mark would be the time to stop maintenance therapy. The only population that you’d be worried about is the high risk population or the ultra high risk population. Maybe those guys have relapsed already by that time and you don’t worry about it, but they would probably need to continue treatment. Thank you so much. Very interesting question.

And then I think we’re down to the last question from Noemí Puig from Salamaca in Spain. Naomi, who is a fantastic world leading expert in myeloma. Thank you for your question. So you are asking about some of these newer diagnostic modalities where we are monitoring myeloma in the peripheral blood and you include cell-free DNA, mass spec and maybe peripheral MRD. And I’d just like to say, Noemí, you’re one of the leading experts in this field and thank you so much for asking my opinion because we really look to you and Bruno in the Spanish group to be really telling us about this. I think essentially my opinion is, let’s start with mass spec. I think mass spec is super important. What mass spec allows you to do is to have a more accurate analysis of the serum M protein in the blood. The reason why this is becoming very important is that we know that serum M proteins, particularly IgGs, have a very long half-life. And it is very difficult to determine complete remission in these patients because of simply the long recirculation of the M protein. And this actually causes lots of problems in clinical trials because of the low levels of MRD-CR that we assign. But also the second point is that we are commonly using CD38 antibodies such as daratumumab and isotuximab and these continue to remain positive. And not all of us have access to the frameshift assays which remove that. And so it’s very difficult to assign a CR in this setting. And mass spec being more sensitive will clearly determine those and give you a higher rate of CR. So I truly believe that we need to start moving away from protein electrophoresis and start move away from immunofixation and start using to mass spec. And there’s different techniques that you could use and it probably doesn’t matter which technique you use, but mass spec is likely to be the way to use modalities. But I think the other key point which you may be eluding to is can we use this in place of bone marrow MRD? And again, the Spanish group is leading the data here. And what we’re seeing is that peripheral residual disease monitoring is complementary to bone marrow MRD monitoring. And one of the pieces of feedback that we keep on getting from our patients is that they want an alternative technique to bone marrow biopsies because it’s uncomfortable and it’s painful. And so I really welcome the work that we’re doing on peripheral residual disease because what it tells us is that we can probably reduce the number of bone marrow samples that we have to do. And we can monitor the patient in a more regular basis using peripheral blood. There are some challenges with the technique and it is undergoing further optimization and you need large amounts of blood, but it’s certainly a really super interesting technique that we can move forward. And I’d really recommend that we continue to study these prospectively in terms of clinical trials. And so I think that’s all the questions.

Thank you all so much for these questions. It’s been such a pleasure talking to you and the VJHemOnc team here at EHA. And I hope that you continue to enjoy the outputs from this congress.

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