Interesting article on the subject:
Lahuerta, J, et al, "Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials," Journal of Clinical Oncology, Sep 2017 (abstract)
Here is the abstract:
Purpose - To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma.
Patients and Methods - Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible multiple myeloma and the GEM2010MAS65 clinical trial for elderly patients with multiple myeloma who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months.
Results - Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with multiple myeloma and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%.
Conclusion - Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with multiple myeloma.
This is a good, related editorial on the article:
Harousseau, J, and Avet-Loiseau, H, "Minimal Residual Disease Negativity Is a New End Point of Myeloma Therapy," Journal of Clinical Oncology, Sep 2017 (full text of article)
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: MRD status vs. complete response for prognostic purposes
Thanks for posting this, Multibilly.
I have to wonder, however, what is really new in this article. Hasn't it been fairly well established by now that, if you have a similar group of patients who are given the same treatment, those who achieve MRD negative status are likely to have longer overall survival? And doesn't this paper just reinforce that finding?
It's also disappointing to see myeloma specialists claim, based on results such as those in the new paper, that MRD negative status "should become a new goal of multiple myeloma treatment", as Harousseau and Avet-Loiseau do in their editorial. As far as I can tell, the paper you cited does not address directly the question of whether or not using MRD negative status as a treatment goal leads to better survival outcomes. Yet, as I know you're aware from previous discussions in the forum on this topic, it's a kindergarten-level statistical fallacy to assume that treating to achieve MRD negative status makes sense just because people who reach MRD negative status live longer than those who do not.
I have to wonder, however, what is really new in this article. Hasn't it been fairly well established by now that, if you have a similar group of patients who are given the same treatment, those who achieve MRD negative status are likely to have longer overall survival? And doesn't this paper just reinforce that finding?
It's also disappointing to see myeloma specialists claim, based on results such as those in the new paper, that MRD negative status "should become a new goal of multiple myeloma treatment", as Harousseau and Avet-Loiseau do in their editorial. As far as I can tell, the paper you cited does not address directly the question of whether or not using MRD negative status as a treatment goal leads to better survival outcomes. Yet, as I know you're aware from previous discussions in the forum on this topic, it's a kindergarten-level statistical fallacy to assume that treating to achieve MRD negative status makes sense just because people who reach MRD negative status live longer than those who do not.
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JimNY
Re: MRD status vs. complete response for prognostic purposes
Hey Jim,
All great points.
I think what struck me (and maybe this was already emphasized in earlier threads), is this point by the authors: "Our results demonstrate that MRD-negative status SURPASSES the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group".
Obviously, neither metric is a guarantee of accurately predicting one's eventual outcome and there is merit in utilizing both approaches when evaluating a patient's response to treatment.
All great points.
I think what struck me (and maybe this was already emphasized in earlier threads), is this point by the authors: "Our results demonstrate that MRD-negative status SURPASSES the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group".
Obviously, neither metric is a guarantee of accurately predicting one's eventual outcome and there is merit in utilizing both approaches when evaluating a patient's response to treatment.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
3 posts
• Page 1 of 1