Case 1: Consolidation Therapy in Myeloma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDAjai Chari, MD:Moving to my clinical colleagues, Ola and Nina, how would you characterize this patient’s presentation, in terms of the stage and prognosis?

C. Ola Landgren, MD, PhD:Well, I looked at all of the details you gave us here. This is a 74-year-old patient who presents with quite good kidney function despite slight hypercalcemia. The creatinine clearance was 61. That’s what you would expect to see in a 25-year-old healthy man. Looking at the M spike of 1.4 grams, that’s not a very high M spike. If you look at the lambda light chains, I’d first like to emphasize that it’s given in a unit of mg/dL. I think that’s always important to look at first—what unit we are talking about. Some labs talk about this as mg/L, and some by mg/dL. That would change the number by a factor of 10. So, with this unit, we see 4.4 mg/dL. That’s just above the threshold, which goes around 2. So, my overall assessment, when it comes to the markers here, is that there’s not a whole lot of release of protein. We heard that the plasma cell infiltration was around 40%.

Just looking at those markers, it suggests to me that this is not a very aggravated situation, with a lot of cranking out of protein that could cause a lot of problems. We hear that it’s a t(14;16) translocation. We don’t know to what degree the cells actually have that, which is something I would like to know. Is this something that’s picked up in 10% or 20% of the cells, or is it in every myeloma cell? Prognostically, that would probably have an important implication. Also, we have to make sure, as we heard from the pathologist, that the correct panel of the FISH [fluorescence in situ hybridization] markers was carried out across the board. At our institution, we would do SNP [single nucleotide polymorphism] arrays and the full panel of all of the markers to make sure that everything is done and to know that it’s negative. Is it missing, or is it negative? I think that’s important.

If you look at the markers here, overall, for the purpose of interpreting what stage we are talking about, we don’t have information regarding albumin. We do have information on the beta-2 microglobulin. If we use staging, which is actually a very old way of thinking about myeloma—it goes back to the 1970s—if you use beta-2 microglobulin, if it’s above 3.5, it cannot be the lowest stage—stage I. But, it has to be over 5.5 to be stage III. If it’s not stage I or stage III, we put it in the stage II category. With the new, revised criteria, you would also look at albumin and LDH [lactic acid dehydrogenase], and you would like to know the FISH cytogenetics. Based on what we know, and in the absence of albumin, I believe this would be a revised high stage II case. You cannot be high-risk cytogenetic and fall into stage I, but you need to have more markers to be a stage III patient.

Ajai Chari, MD:I think that’s an important point, at which the universality of the ISS [International Staging System] was limited by the lack of molecular information. And, as you alluded to, integration with the LDH and FISH is really helpful, in terms of risk stratification.

C. Ola Landgren, MD, PhD:I would like to add one last thing to this staging literature. I do think that it’s very important to recognize that all of these models are based on old data. When we talk about survival outcomes for stage I, stage II, or stage III patients, for whichever model we use, the outcomes are based on what therapy the patients were given.

Ajai Chari, MD:Absolutely.

C. Ola Landgren, MD, PhD:There is a lot of evidence from the literature that suggests that if you apply these scores to patients who were treated with really old therapy, you could see big differences between stage I, stage II, and stage III. But, if you look at the more modern therapies, there is very little difference. If you use the best therapies that we have, there is virtually no difference between stage I, stage II, and stage III. With the new, revised criteria, if you have adverse features of the disease, that still can make a difference. I want to caution that the number of months of follow up is not written in stone. It’s really dependent on the therapy.

Ajai Chari, MD:That’s an excellent point. Prognosis is dependent on treatment.

C. Ola Landgren, MD, PhD:Yes.

Transcript edited for clarity.