Myeloma : treatment progress and revolution in the strategies

sciencepics/epictura

Published the 10.12.2017 to 03: 00

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Keywords :

myélomeMDRmaladie résiduellestratégie

The recent increase in the number of different therapeutic combinations validated for patients with multiple myeloma is accompanied by a revolution in the evaluation of their effect on the disease and the level of the remission. The accurate measurement of the depth of the remission under these treatments opens the door to a complete redefinition of the objectives of the treatment.
Studies and analyses recent show in fact that a minimal residual disease (MRD) negative is associated with a progression-free survival and an overall survival longer in patients with multiple myeloma. With the use of therapeutic strategies modern, more than 60 percent of patients with multiple myeloma newly diagnosed achieve complete responses, and an MRD negative.

There is no small myeloma

New data indicate that between 90 and 95% of patients with an early form of myeloma early (” smoldering myeloma “), may obtain complete responses, and an MRD negative.
To Professor Ola Landgren, there is no form of myeloma that does not require treatment. It is not necessary to wait for clinical signs, such as fractures or encroachment of spinal cord major to consider that a person is sick and treat it. All of the data that he presented in a session controversies in the ASH suggest that the treatment results in terms of mass residual tumor and duration of remission, are all the best that the treatment is early and that the tumor mass is low. It is suggested, therefore, treat the myeloma very early with the most effective treatments in order to try to eradicate the disease.
At present, however, there is no evidence that this treatment strategy of early intensive be able to completely eradicate the disease. Some experts have also pointed out that there are still a clone of tumor cells that are naturally resistant to treatment, or which become, and are likely to persist. A number of experts still think that, for the comfort of the sick, it is better to treat the myeloma when it becomes scalable, with the possibility of follow myeloma towed on markers more sensitive than the clinical signs, biological, and radiological traditional in order to make a treatment decision before the tumor mass is too large.

The promises of residual disease minimal

Residual disease minimal, or MRD, is a concept that allows you to assess the quality and depth of the response to treatment.
It is determined by techniques, ultra-sensitive detection of myeloma cells in the marrow. There are many techniques for assays of these cells, including the genetic sequencing of the new generation, or NGS (” Next Generation Sequencing “), or a new technique standardized flow cytometry as the so-called ” Next Generation Flow Cytometry “.
The sensitivity of these techniques is such that they are capable of detecting a single cell myélomateuse on a million cells of the bone marrow. This threshold of 10-6, seems to be the threshold at which experts define a remission bone marrow relevant to the disease because this threshold is associated to a real difference in prognosis and survival.
This threshold is so discriminating, that patients are able to achieve a BN to 10-6 without any bone marrow transplant, “the nuclear weapon” of myeloma treatment, are able to have the same prognosis as those who have been grafted in. Moreover, if we look at the patients who have a lot of genetic abnormalities prognosis is poor, those who achieve an MRD negative have a better prognosis than those who do not reach the threshold of 10-6. The BN is, finally, a dynamic concept that works regardless of the stage of the disease and allows the long-term monitoring. Finally, the MRD 10-6 is also a threshold that is associated with a significant increase in survival without disease progression (PFS) but also overall survival, that is to say, the survival real of the sick.

A change of strategies

The progress of myeloma treatments currently posed to the hematologists a problem of a paradox : the prolongation of the overall survival and progression-free survival increases the length and cost of studies in myeloma since the criterion of judgment is currently the relapse, and that it can take 7, 8 or 9 years old. This extension of the therapeutic trials until this term represents a debauchery of financial resources and a loss of opportunity for many people.
The next-generation sequencing, which becomes accessible and the definition of the MDR with a threshold of 10-6 can be a biomarker highly sensitive which should allow, in future clinical trials, to adjust the treatment of residual disease minimal without waiting for clinical relapse or biological. This technique of NGS has a cost, of course, but if it can diagnose very quickly that an expensive treatment does not produce a MDR or the MDR goes back under this treatment, it is possible to stop it immediately and change immediately to another more effective treatment. In the same way, if after induction therapy, what it is, a BN 10-6 is reached, it can be discussed to make only a transplant and not 2, or even not to transplant any, to the reserve in a later phase of the disease.
Considering the cost of new treatments and the transplant, the cost to society is reduced, and avoids the need to undergo unnecessary treatment to the patient. Thus, we see in the myeloma the advent of a chronic treatment adjusted to each phase of the disease, according to a goal of MDR to 10-6. The evaluation of the MDR will allow for these adjustments early to rise as soon as the slightest recovery of the disease is that it will allow periods where the patient will remain without maintenance treatment and under simple monitoring.

Re-discussion of maintenance treatments systematic

In a presentation that closes this session, it is apparent that there is no assurance that these maintenance treatments will be necessary for all patients.
When I get back in the major therapeutic trials, which have promoted the treatment of maintenance with lenalidomide for example, we see that they are very heterogeneous on the one hand (all of the trials show no benefit), and that the benefit in terms of survival is modest and puts a lot of time to express themselves (it takes several years to see a significant difference). A phenomenon all the more annoying that the lenalidomide in long-term treatment is accompanied by an increase in secondary cancers.
In view of these data, the experts considered the data of individual patients from different studies, and in dividing the sick by more homogeneous groups according to various criteria of gravity, it will demonstrate that maintenance treatment with lenalidomide would be of no benefit in patients without criteria of severity. The benefit does not appear that in patients in good general condition who have poor prognostic factors (genetic factors, etc.). Again, the use of the MDR should help to stop any maintenance treatment in patients in remission with complete spinal cord because this technique will resume with the right treatment at the slightest sign of recovery of the disease in the marrow.

The last 10 years have been exciting and full of hope for patients with myeloma and this announcement is even more exciting. We now have a lot of molecules, high-performance and new tools are arriving to help best serve. After having more than doubled the life expectancy of patients with myeloma, the blood disease gradually becomes a chronic disease and the healing of some patients becomes possible.