What is the International Myeloma Working Group (IMWG) criteria for the diagnosis of active myeloma?

What is the International Myeloma Working Group criteria for the diagnosis of active myeloma?

So to answer your first question about myeloma defining events, which at one time were also called CRAB symptoms. CRAB, as you know, were the acronym used to define those four symptoms or criteria that would help us make the diagnosis of symptomatic myeloma. In other words, patients with multiple myeloma who we think would require clinical treatment.

CRAB, as it was called, basically an acronym where C stood for high calcium. And that was defined as greater than one milligram per deciliter above the upper limit of normal or greater than 11 milligrams per deciliter. So high calcium was one. R stood for renal insufficiency or inadequate kidney function. And again there are criteria for defining those, including serum creatinine level, which is a reflection of kidney function and is greater than two milligrams per deciliter.

The A of the CRAB criteria was anemia, which was basically a drop in hemoglobin greater than two grams below the lower limit of normal, or the total hemoglobin would be less than ten grams per deciliter. The B of the CRAB criteria was bone lesions. As you know, myeloma patients can present with bone changes with thinning of the bone, as well as sometimes fractures that we call pathologic fractures.

So those bone lesions, one or more, if they were picked up on either an X-ray or CT scan or PET scan. So these were the CRAB criteria. But then the experts realized that there were actually other features that tell us that these patients actually required treatment. And when they looked at the data, they came up with three additional features, of course, with seven features.

Now, we could not totally use that acronym CRAB. So those seven features now became myeloma defining events. In addition to the four CRAB features that I already pointed out, the three additional features are:

number one is 60% clonal plasma cells in the bone marrow. So if you do a bone marrow biopsy, of course we know in multiple myeloma the malignant cells are the plasma cells. So if, under the microscope, 60% of those cells or more are plasma cells. And then we have to show that they are coming from a clone of cells, malignant cells, which can be determined by immunohistochemistry or flow cytometry, showing that these are all expressing only one type of light gene. So that would be the clonal plasma cells.

So 60% or more is one of the newer myeloma defining events. Two additional myeloma defining events: one is the light chain ratios we measured serum free kappa and free lambda light chain. If the patient has, say, kappa light chain type of myeloma, the ratio of kappa to lambda should be more than 100, with the kappa light chain level itself should be more than 100 milligrams per liter.

So that would be the second myeloma defining event. In addition to the four CRAB criteria, the final myeloma defining event is the MRI lesion. So when we do the MRI, if we see more than one focal lesion, in an MRI, you see different features than what you see on the bone X-ray. So if you see more than one focal lesion in a myeloma patient on MRI, each measuring five millimeters or more, it is considered a myeloma defining event.

So in summary, we have CRAB criteria plus these three myeloma defining events, which are 60% clonal plasma cells, involved to uninvolved light chain ratio of greater than 100, and more than one focal lesion on the MRI.