Why is a bone marrow biopsy (BMB) necessary? What testing is done on the BMB sample?

What is a bone marrow biopsy?

Why are they necessary?

What testing is done on the bone marrow biopsy sample?

So a bone marrow biopsy is basically a procedure where we go into the bone marrow and get a sample of bone marrow from inside your bones. That's where all the blood cells are made; all your blood cells are produced there. Bone marrow biopsies are extremely critical for the diagnosis of multiple myeloma because that's where the plasma cells are, you know, the cancerous ones. To be able to diagnose the disease, you need a bone marrow biopsy.

It's important not just for quantification. It gives us a sense of how many plasma cells are present in the bone marrow and what the burden of disease is. So that's one reason why we get the biopsy at baseline. The more important reason is to look at the genetics of those myeloma cells. We are now able to do several genetic tests called FISH tests on that bone marrow sample, which then gives us a stage. Your staging is now incorporated into your FISH results, meaning some patients may have high-risk mutations present in their myeloma cells while others have more standard-risk mutations. We cannot get that information outside of some research labs; we can only obtain it through a bone marrow biopsy.

So it’s really critical, again, for quantification and also to determine the genetics of your individual disease.

When and how often should a bone marrow biopsy be done?

We obviously want a diagnosis for the reasons I just mentioned. Going forward, it depends on what information we're trying to get out of the bone marrow biopsy. If a patient is in a great disease response, for example, and we can measure that using blood tests, such as their light chains or M protein concentrations, that gives us a sense of what’s going on most of the time in the bone marrow. But to truly know if the disease is no longer present at a detectable level, we sometimes need to confirm whether they have had what we call a complete response or complete remission.

That’s one phase where it’s done as patients start therapy. We’ve also recently seen data with MRD or minimal residual disease. What that is, is a test done on the bone marrow specimen to look for a certain sequence that the myeloma cells have. Now we can detect it at a very deep level in one in a million cells using that MRD test. That’s another space where there’s a test now approved, which can provide prognostic information about a patient’s disease.

Then at the time of relapse, when patients experience a disease relapse, we do recommend a bone marrow biopsy. The reason for that is we want to see what’s changed. It usually confirms the recurrence of those plasma cells, but the genetics may be different. If you have one diagnosis and one at relapse, we can then compare to see what new mutations a patient may have acquired, which can affect the aggressiveness of the disease at that moment and dictate the type of therapy we may choose.

If my doctor can tell I have myeloma from my blood work and imaging, why is a bone marrow biopsy necessary?

This comes up a lot, and it’s true that there are certain criteria where just by blood tests or imaging alone, you can confirm a diagnosis of multiple myeloma. For example, if the kappa to lambda light chain ratio is widely off or if there are lytic lesions that seem to match the diagnosis of myeloma, I would consider that myeloma defining. However, the bone marrow biopsy is imperative.

I hope for a world where we have better blood assays to assess this, but we're not there yet. The important part to remember is that the light chains are not the cancer; they are a protein produced by the cancer cells and serve as a biomarker. They’re helpful because they’re easy to check through bloodwork, but for major decision-making—such as at diagnosis—it’s essential to get a good look at the cancer cells themselves to see what’s going on.

What does a bone marrow biopsy do?

It shows us what’s going on inside the bone marrow. There are several things that could dramatically change my management based on what I see in there. The most important example is FISH, or Fluorescence In Situ Hybridization. Sometimes the myeloma cells have certain genetic or chromosomal abnormalities that render them more resistant to traditional therapies. You may know from other videos about standard risk versus high risk; that’s what I’m talking about. You cannot determine standard versus high risk from blood testing; that information comes from the bone marrow biopsy.

This does change management for patients with high-risk myeloma. I may approach transplant differently or use different drugs or consolidation strategies. Other useful information from the bone marrow biopsy is important, too. There have been cases where I’ve seen other issues going on, such as AL amyloidosis, which involves proteins forming clumps and can cause problems.

So those are two reasons to conduct the biopsy: understanding the higher risk genetics and identifying other conditions. Also, knowing where we started can be beneficial. At the end of the day, the light chains are not the cancer; the cancer is the myeloma itself. If you know what percentage of the bone marrow was involved by the myeloma at the beginning, it provides a good comparison for evaluating progress later on.

Regarding measurable residual disease (MRD), it’s worth noting that the field is rapidly evolving. Currently, the most commonly used MRD assays are based on bone marrow samples. For instance, next-generation sequencing, often done by a company called Adaptive, requires the initial bone marrow biopsy to fingerprint the myeloma cells by identifying unique DNA sequences.

In summary, there are many reasons why a bone marrow biopsy is imperative. The biggest reason is understanding the standard as a result of genetics. Additionally, it helps us look for other abnormalities and provides useful information for future testing, such as MRD assays.

Why are bone marrow biopsies repeated periodically after the initial bone marrow biopsy at diagnosis?

Until we find a better way to evaluate disease biology, bone marrow biopsies will remain an important part of your journey with myeloma. Each time myeloma recurs, the disease biology is different from before. It’s essential for us to understand this evolution. We are starting to differentiate what therapies patients need for certain subsets, which is crucial.

Myeloma is not one disease; even within a given patient, it can manifest differently. Different clones of myeloma can emerge over time. As the disease evolves, it’s important to keep track of these changes. Patients can develop new abnormalities that weren’t present at the time of diagnosis, and we won’t know about them unless we perform repeat biopsies.

Most myeloma centers conduct cytogenetics, FISH panels, and flow cytometry as standard of care, along with looking at specific markers on the bone marrow sample. Gene mutational panels are also performed in the context of certain clinical trials or projects to identify specific gene mutations that patients may have.