Rethinking testing in multiple myeloma
NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.
“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.
“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”
To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.
“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.
Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.
Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.
“But still, 2 patients in the same box based on clinical features will often have very different outcomes,” he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”
Methods to assess myeloma cell proliferation
Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.
To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”
If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.
“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”
Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).
Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.
It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”
In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.
In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.
“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”
And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.
Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.
Plasma cell proliferation indices
Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.
