How is active myeloma defined?

[Music] how is active myeloma defined to answer your first question about myeloma defining events which at one time were also called Krabbe symptoms so crab as you know were the acronym used to define those four symptoms or criteria that would help us making the diagnosis of symptomatic myeloma in other words patients with multiple myeloma who we think would require clinical treatment crab as it was called was basically an acronym where si stood for high calcium and that was defined as a greater than one milligram per deciliter or above the upper limit of normal or greater than eleven milligram per deciliter so high calcium was one R stood for renal insufficiency kidney problem or inadequate kidney function and again there are criteria for defining those including serum creatinine level which is a reflection of kidney function which is greater than two milligram per deciliter the a of the crab criteria was anemia which was basically a drop in hemoglobin which was greater than two gram below the lower limit of normal or the total hemoglobin would be less than ten gram but deciliter the me 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 they were actually other features that tell us that these patients actually require treatment and when they looked at the data they came up with 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 so 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 our 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 chain so that would be the clonal plasma cell so 60% or more is one of the newer myeloma defining event two additional myeloma defining events one is the light chain regressed ratios we measure serum free Kappa and free lambda light chain if the patient has say Kappa light chain type of myeloma the ratio of capital lambda should be more than 100 with the Kappa light chain level itself should be more than 100 a 100 milligram per liter so that would be second myeloma defining event in addition to the four crab criteria and the final myeloma defining event is the MRI lesions 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 millimeter or more it is considered myeloma defining event so in summary we have crab criteria plus these three myeloma defining events which are he percent coronal plasma cells involved two uninvolved light chain ratio of greater than 100 and more than one focal lesion on the MRI how is action of myeloma defined using the Sun crab criteria so when patients initially present with a plasma cell disorder we have to characterize whether or not someone has a precursor condition such as MgO smoldering myeloma or whether or not they have a systemic myeloma that requires treatment the actual level of M protein that defines myeloma technically speaking is three grams per deciliter but practically speaking the level of that M spike protein is not in and of itself sufficient to identify individuals that require treatment that the myeloma defining events as they have been recently relatively recently updated include presence of what we call crab criteria hypercalcemia renal disease anemia bone disease or several myeloma defining events including focal abnormalities on an MRI a bone marrow plasma cell percentage above 60% and a free light chain ratio over a hundred with the involved light chain being 10 milligrams per deciliter or greater so on some level the free light chain ratio in and of itself may be a myeloma defining event or has been characterized as a myeloma defining event so with a ratio over a hundred and an involved free light chain over ten one needs to discuss with their physician whether or not it's appropriate to initiate myeloma treatment at that time a similar number for M spike doesn't exist per se however if one has on serial examinations several two three or four sequential examinations over a limited period of time rising mzm protein that does suggest that one needs to revisit the question of whether or not any additional crab criteria or my little defining events are present because that's a situation we're trying to prevent systemic issues developing from the diseases is important [Music]