What is the response criteria in myeloma?

So it comes to the response criteria of multiple myeloma. There are a lot of challenges obviously for patients to understand. In summary, it is basically showing how much of the myeloma that was there in the beginning of the total sum and mass of cells. How much has that been reduced?

The least step that we can show is a 25% reduction. Usually what we measure is the monoclonal protein in serum and in urine. When you have 25% reduction or more than we call it, at least a minimal response. In patients who have 50% reduction, we call it a partial response. In patients who have a 90% reduction, and it's a bit more complex than that. But in general, we can say that a 90% reduction is so-called very good partial remission.

And if we cannot measure anything anymore in blood and urine with the most sensitive techniques that we have, then we call it a complete remission. To have this criteria, we also have to do a bone marrow biopsy and show that there's less than 5% plasma cells in the bone marrow that would complete the complete remission definition.

What we also have is a so-called stringent complete remission, where also the ratio of the light chains is negative. And in the immunohistochemistry and from the bone marrow, we see that there are no monoclonal plasma cells left to no cancerous cells left with microscopy.

The next step is to minimal residual disease negativity. And there are also different levels. But the most important is to know that we use machines like either next generation sequencing or next generation flow cytometry, where we put a number, a large number of cells, for example, 100,000 or 1 million cells. And if there is no myeloma cell in this 100,000 or 1 million cells, then we call it minimal residual disease negativity.

And we also have to at what sensitivity did we use. And the less important factor is that we do imaging. We do usually PET-CT all for follow up. And we see if the PET-CT is negative. We call it imaging negative. And we know that if we do MRD assessment from the bone marrow, we also have to do an imaging because we might miss something, because the bone marrow biopsy is only one area where we do the biopsy. It is very representative, but it's not 100%.

So it makes sense to do a bone marrow biopsy for MRD assessment plus an imaging. And if both are negative, we know the patients have a very good prognosis.

And the last thing I want to mention is that some patients have kind of sequential MRD assessments from the bone marrow biopsies, for example, 6 or 12 months apart. And if they are both negative for MRD assessment, then we call it sustained MRD negativity. And in a lot of studies, and even here at ASH meeting in 2021, we can see that patients with sustained MRD negativity have the best prognosis all.

Are remission and response the same?

What does it mean to be in remission? Oftentimes confusion amongst patients. They are very surprised if they tell them they have achieved a remission. There's not really as much of a difference between response and remission. Response is to therapy. Remission is the remaining amount of myeloma. But the response basically leads to the remission.

And I personally tell my patients, and it might be a little bit more philosophical than the research question, that even a partial remission is a remission, and even a minimal remission, minimal response is a remission. It is, of course, we want to achieve the deepest remission possible because that's the closest to a cure we can come. But I think even achieving a reduction, especially later in lines of treatment, it's helpful to achieve some kind of remission.

And then there's even in clinical trials, sometimes, there are clinical response rates or risk, clinical benefit rates, which show that the patient stays stable in a certain area and patients who had a lot of lines of treatment. Sometimes we are even happy to just keep them on a low level of disease that doesn't harm their body. And they can still survive longer.

The International Myeloma Working Group developed a standardized response criteria that is used worldwide. This chart summarizes the criteria needed for each level or response. The International Myeloma Working Group established this criteria in order to facilitate precise comparisons of efficacy between new treatment strategies in trials, incorporate the serum free light chain assay to include assessment of patients with oligo secretory and non-secretory disease, provide stricter definitions of CR complete response, provide classifications that would improve detail and correct inconsistencies in prior response criteria.

This criteria reconcile various previously used systems for assessing response and has been universally adopted.