Name:
MRD in multiple myeloma: an interview with Rafael Alonso
Description:
MRD in multiple myeloma: an interview with Rafael Alonso
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Upload Date:
2023-02-12T00:00:00.0000000
Transcript:
Language: EN.
Segment:0 .
[AUDIO LOGO]
RAFAEL ALONSO: Minimal Residual Disease or MRD refers to the malignant plasma cells that persist in the bone marrow during or after treatment. During the past 30 years, we have recognized that the achievement of complete response was associated with superior survival results. Now we know that some patients seeing CR still have persistent residual disease, increasing the risk for early relapse. Meanwhile, patients in CR, with the MRD negativity have shown greater durability.
RAFAEL ALONSO: And nowadays, sustained MRD negativity sequential assessments is the deepest level of response to multiple myeloma. And it is associated with prolonged PFS and OS. As discussed, this evidence further shows that MRD negativity surpasses a complete response as the strongest predictor of improved long-term outcomes. Thus, the goal of the treatment for most myeloma patients should be to go beyond VGPR or CR and try to achieve deeper and longer responses with - of course, with MRD negativity whenever possible.
RAFAEL ALONSO: MRD should be our treatment goal. Traditionally, treating to achieve the deepest response has meant treating to CR. However, the level of residual disease left undetected by complete response confounds the clarity of this goal. So the first line of treatment, in my opinion, is the most important, since some patients do not make it to later lines.
RAFAEL ALONSO: And it is the time when we can potentially obtain the longest PFS. Likely, the outcomes will be poorer in subsequent lines of treatment, probably, due to the increased genetic complexity and even clonal evolution. Thus, in my opinion, MRD negativity should be a key goal in frontline therapy. We should seek to achieve the deepest response for most patients, perhaps, only excluding frail or very frail patients.
RAFAEL ALONSO: The association of MRD negativity with prolonged PFS and OS has been demonstrated in both the transplant-eligible and transplant-ineligible populations in general for newly diagnosed patients who want to aim at MRD negativity at the deepest level of treatment responses. So for transplant eligible patients, we may be able to treat them more aggressively.
RAFAEL ALONSO: MRD negativity is a clear goal. The aim of induction therapy is attaining very deep responses, which could be prolonged and even deepened with transplant and a subsequent maintenance treatment. This management allows better long-term outcomes. But among transplant-ineligible patients, there will likely be a subset whose age, frailty, and comorbidities may challenge the usefulness of MRD negativity as a treatment goal.
RAFAEL ALONSO: That said, there will be still many patients not receiving transplant who have an urgent need for high efficacious and tolerable therapies, capable of driving MRD negativity and extending remissions. But globally, and given the importance of getting very deep responses in newly diagnosed multiple myeloma patients, for me, it makes sense for frontline therapies to evaluate their ability to generate high rates of MRD negativity.
RAFAEL ALONSO: I think that, in addition to other efficacy endpoints, MRD negativity rate is useful information about the depth of response. And with MRD negativity being the deepest level of treatment response currently measured in myeloma, and with evidence showing a strong correlation with improved PFS and OS, we should expect that treatments delivering high rates of MRD negativity could give patients a chance for improved long-term outcomes.
RAFAEL ALONSO: Well, in my center, we incorporated MRD to our daily life some years ago. And we have noted its prognostic value in a real-world setting. Thus, and in accordance with the goal, for me, achieving MRD negativity is the goal of the treatment for most of newly diagnosed myeloma patients and even for patients in first relapses, when I'm trying to deliver an intensive treatment.
RAFAEL ALONSO: From my point of view and based on my personal experience, it is key and very useful to be aware of three points. The first point is a single measure of MRD negativity is not enough. I think we should pursue the sustained MRD negativity as the deepest disease response that we can obtain in multiple myeloma, even according to International Myeloma Working Group criteria. The second point is, a single measure of MRD negativity is not enough, again, because the kinetics of MRD in subsequent assessments over time is even more informative.
RAFAEL ALONSO: And recent studies are supporting this response and its relevance. The third point, a single measure of MRD negativity is not enough for the third time. And likely, we can broaden its prognostic value by combining it with imaging techniques, as PET/CT or diffusion-weighted MRI. And who knows, maybe, in the future with novel techniques as mass spectrometry or liquid biopsy.
RAFAEL ALONSO: I think that all the ongoing studies evaluating the role of MRD will be crucial in the next few years. I think, they will help us to understand the best way to involve MRD in clinical decision-making.