“However, it is now urgent to define and incorporate MRD into our response criteria more generally, since combination novel therapies, with or without autologous stem cell transplant (ASCT), can now achieve MRD”
Dr. Ken Anderson doesn’t come out and say that multiple myeloma (MM) patients achieving minimal residual disease (negative) status post induction therapy, can eliminate the need for further toxic treatment. But his article leads the reader to that conclusion.
After all, only one of the most senior, world-renown, experienced MM specialists could question the need for a standard-of-care therapy that costs hundreds of thousands of dollars, causes extensive short, long-term and late stage side effects yet does not add to the overall survival of multiple myeloma patients.
Your response to your induction therapy will tell you about your average overall survival. Meaning, those patients who achieve a good response to induction therapy- MRD, sCR, CR or VGPR, according to research, have the best odds of having a long overall survival (length of life).
It is those patients who do not achieve those positive responses to induction therapy that should give serious consideration to an autologous stem cell transplant.
Question-if you reached MRD (negative) status after 4-6 rounds of induction therapy and you read a study confirming that additional chemotherapy, on average, would not increase your overall survival, would you then have an autologous stem cell transplant?
Further, according to Dr. Anderson below, novel therapies make it possible for relapsed MM patients to achieve MRD.
To be clear, achieving MRD negative status requires aggressive chemo. I’m not saying for a minute, that achieving MRD is easy. But the day may come when studies compare quadruplet induction to an ASCT and conclude that the novel therapies cause less damage and cost less money.
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“Traditionally, complete response (CR) in MM has required absence of monoclonal protein by sensitive immunofixation techniques and normalization of the BM. This definition was then refined by the IMWG to stringent CR, which also required a normal κ:λ ratio.
Importantly, due to the unprecedented depth of responses now achievable with novel therapies with or without high-dose therapy and transplantation, the IMWG has most recently further defined the consensus criteria for response and minimal residual disease (MRD) response assessment.28
In the setting of conventional CR, absence of detectable MM using either next-generation flow cytometry or by next-generation sequencing (both with a sensitivity of detection of 1 in 105 nucleated cells or better) now defines flow or sequencing negative MRD, respectively.
By IMWG criteria, sustained MRD negativity requires 2 such determinations 1 year apart. Finally, an imaging MRD-negative response in addition requires resolution of all areas of increased tracer uptake on positron emission tomography/computed tomography scan…
Until recently, MRD negativity was obtainable primarily in the context of allogeneic stem cell transplantation, where sustained MRD negativity due to a donor graft-versus-MM effect is associated with long-term disease-free survival and cure.29–31
However, it is now urgent to define and incorporate MRD into our response criteria more generally, since combination novel therapies, with or without autologous stem cell transplant (ASCT), can now achieve MRD…
For example, in the Inter-Groupe Francophone du Myelome and Dana-Farber Cancer Institute (IFM/DFCI) clinical trial of lenalidomide, bortezomib, and dexamethasone induction therapy with or without early ASCT followed by 1 year of lenalidomide maintenance, 80% and 60% patients achieved MRD with or without early transplant, respectively.32…
Importantly, this study further showed that MRD status after maintenance therapy was associated with PFS and suggested a threshold of sensitivity of 10−6 to define MRD negativity.
Excitingly, daratumumab in combination with either lenalidomide or bortezomib and dexamethasone can achieve MRD even in relapsed disease.18,19—
MRD negativity was associated with improved PFS and OS, both overall (P < .001) and in patients who were in CR (P < .001). Although there was some overlap in the clinical studies included in the second meta-analysis, Landgren et al39 similarly found a statistically significant correlation between MRD negativity and both PFS (P < .001) and OS (P < .001)…
My wife has Plasma Cell Leukemia (aka Acute Myeloid Leukemia). She currently is “in remission ” after 5 months of therapy, and has started maintenance therapy. She is not going to have a stem cell transplant. Do you think these therapies would be appropriate for her?Reply