Top myeloma clinicians, Dr. Joseph Mikhael, an IMF Medical Advisor and Professor in the Applied Cancer Research and Drug Discovery Division at TGen at the City of Hope, and Dr. Ola Landgren of the University of Miami, Sylvester Comprehensive Cancer Center, discuss five key topics in the field of multiple myeloma. 

(EDITOR'S NOTE: Top myeloma clinicians, Dr. Joseph Mikhael, IMF Medical Advisor and Professor in the Applied Cancer Research and Drug Discovery Division at TGen at the City of Hope, and Dr. Ola Landgren of the University of Miami, Sylvester Comprehensive Cancer Center, discussed the five key topics in multiple myeloma on March 14, 2026. This discussion was part of the many sessions conducted during the IMF Patient and Family Seminar held in Boca Raton, FL. Topics discussed have been edited for conciseness and clarity.) 

Scope and Methodology

This article summarizes a discussion between leading multiple myeloma specialists, Dr. Joseph Mikhael and Dr. Ola Landgren, presented during the 2026 International Myeloma Foundation (IMF) Patient & Family Seminar in Boca Raton, Florida. The content reflects their expert perspectives on current standards of care, emerging diagnostic technologies, treatment strategies, and future directions in multiple myeloma research. Information has been edited for clarity and accuracy while preserving the scientific intent of the discussion. References to clinical trials, FDA approvals, and evolving treatment approaches are presented for educational purposes and should not be interpreted as individualized medical advice. Patients should consult their healthcare team to determine the most appropriate diagnostic and treatment options for their specific situation.

1. Diagnostic Imaging for Multiple Myeloma: Where is it Headed? 

“Skeletal surveys used to be the standard of care [but this is no longer the case]. We know that a CT scan by itself is about 30 times more sensitive than X-ray alone. So, a very simple way of thinking about it is, if you take an X-ray, you take a picture through a bone, then you look at it, and the bone is denser than the surrounding air,” Dr. Landgren said.

The question is: How much does it take for the bone to have a hole in it in order for this technology to see the difference that there is a gray instead of a black, which is about 50% of the bone being gone?

“It must be a dramatic hole before you can even see it on X-ray. That’s why we use PET scan or a CT scan. They are much more sensitive. Even a few millimeters of a hole would be picked up by a CT can. This is why CT scans should be the standard of care and not X-rays,” answered Dr. Landgren.

“I used to be on the NCCN Guidelines Committee when I worked on lung cancer, and we changed the guidelines. Still, I think there were some insurance companies still pushing back, saying you have to do an X-ray before a CT-scan, but this is really not appropriate. The guidelines state that you don’t need to do it, so doctors should push back [against] that,” he further explained. 

PET-CT Scan vs. CT Scan 

“PET-CT is really a CT.  You take pictures in this tunnel where you take pictures from different directions. Plus, you inject glucose. The PET tracer is not dye; it's glucose. The glucose is labeled. You can actually see it in the machine. This is important because PET-CT scans were developed on the assumption that glucose can distinguish abnormal from normal cells,” said Dr. Landgren.

“The idea behind PET scan safety a long time ago was if you have a disease that grows faster than the normal surrounding tissue, it will presumably eat more glucose,” he further explained.

According to Dr. Landgren, if you label glucose and image it, you can see increased uptake over time—those areas appear “hot.” However, this isn’t true for every disease. In myeloma, for example, even among 10 patients with truly lytic lesions, about 7 will show detectable lesions, while 3 will not. When are MRIs the better imaging tool in myeloma?

Dr. Landgren explained that "the skeleton is made up of bone and bone marrow. CT scans are good to use [in bone imaging]." CT scans don't work well on bone marrow because they are softer than bone. Using an MRI machine for bone marrow imaging is much better. 

What is the standard of care for diagnostic imaging in myeloma?

To check for smoldering myeloma or active myeloma, or to make sure that there is no relapse, the best tool to use would be a standard PET- CT scan, according to Dr. Landgren.

"If the test comes out negative, we may add an MRI without contrast to make sure that there are no changes in the bone marrow," he further added.

The future of myeloma diagnostic imaging

In terms of myeloma diagnostic imaging, Dr. Joseph Mikhael thinks that targeted imaging will come into play in the future. Targeted imaging techniques will use molecular or biologic markers to specifically detect myeloma cells or their activity—rather than just showing structural damage like bone lesions.

It differs from standard imaging (like X-rays, CT, or MRI), which only show bone damage and/or tumor size or location. Targeted imaging goes further by highlighting active myeloma cells, metabolic activity, and specific proteins or receptors on tumor cells. 

2. Mass Spectrometry vs. Serum Protein Electrophoresis (SPEP): Which is Better?

Dr. Landgren and Dr. Mikhael discussed this question at length: “Do you think mass spectrometry (mass spec) is going to be a big part of what we do in the future, or do you think we’ll still be doing serum protein electrophoresis (SPEP)?”

Mass spectrometry received its first FDA approval in 2025, but it is not yet approved for baseline characterization of M spikes in light chains or for disease tracking.

First-generation systems use MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization–Time of Flight), such as Mayo Clinic’s version. These detect immunoglobulin fragments and are 10–100× more sensitive than immunofixation, but sensitivity introduces challenges: detecting very low protein levels is complicated by abundant background proteins in the blood, especially albumin.

This creates a signal-to-noise problem—disease signals can be obscured by normal proteins. More targeted approaches can reduce this issue. One newer method uses a patient’s unique genetic fingerprint to predict and detect disease-specific “clonal peptides.” Their presence indicates disease; absence suggests none. This approach is over 1,000× more sensitive.

At the University of Miami, both technologies are now available. Starting in 2026, they will be offered to all patients as research tests, with costs covered internally to generate data and accelerate progress in the myeloma field, though they are not yet approved for standard clinical use.

“A blood test or SPEP is what your doctor probably asks you to take, a week before your visit.  Some of these tests can be done with the right machinery in 15 minutes, so the day may come when it will be faster and more accurate because we’ll be able to detect small amounts,” said Dr. Mikhael  

For example, you may ask: Why do I still have this little M spike of 0.2?

According to Dr. Mikhael, the M spike of 0.2 “is the drug you're being given, not the disease.”  

He said that some of these technologies:  

• will look at the tiny amounts of disease,
• will be able to discriminate the disease from the therapies, and  
• will be able to do all these things faster.

“While not ready for prime time, I’m glad Dr. Landgren’s lab is collecting this information now, so we can inform the community,” said Dr. Mikhael.  He believes that sooner than later, SPEP may be replaced by technology that does tests more accurately.  

“It's not clear to me that protein tests will remain. They may be replaced by other tests. The good thing is that a lot of people are pushing this forward. And the field is going very fast. I'm very optimistic about this,” Dr. Landgren said.  

3. Will Quadruplets Remain the Standard of Care in Multiple Myeloma?

A quadruplet combination means that there are four different drugs that are being used for treatment which typically includes a monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug, and dexamethasone, as a steroid. The quadruplet has become a standard of care for most patients, though not all, explained Dr. Mikhael.

Dr. Landgren explained that treatment for multiple myeloma has steadily evolved over time. In the early 2000s, patients were treated with two-drug combinations such as bortezomib (Velcade) plus dexamethasone or lenalidomide (Revlimid) plus dexamethasone. By 2010, a three-drug combination—bortezomib, lenalidomide, and dexamethasone (VRd)—became the standard of care and remained widely used for about a decade.

More recently, researchers began adding a fourth drug, such as the antibody daratumumab, to improve outcomes. Studies like the GRIFFIN trial showed that combining four drugs could be more effective than three, leading to a wave of similar approaches that “stack” additional therapies together.

However, Dr. Landgren noted that simply adding more drugs may not always be the best strategy. Instead, researchers are now exploring whether newer, more powerful treatments could allow for simpler regimens. For example, current studies are testing combinations that include a bispecific antibody, an immunomodulatory drug, and very low doses of steroids—often stopping steroids early and sometimes adding a proteasome inhibitor only when needed.

Early results suggest that these streamlined combinations can still produce strong responses. Dr. Landgren believes the future of treatment may focus on using fewer, more effective drugs rather than continuing to add more medications to existing regimens.

Dr. Landgren said he has been closely involved in research on high-risk smoldering multiple myeloma for many years, including leading the CENTAURUS trial and overseeing safety for the AQUILA trial. These studies showed that treatment can reduce the risk of disease progression by more than 50%.

However, he pointed out that only about 8% of patients achieve full remission, meaning most still have some remaining disease. In many cases, treatment helps control the condition rather than eliminate it.

This led researchers to explore whether adding another drug could improve outcomes. Dr. Landgren and his team have studied combinations that include daratumumab and are now running a newer trial for patients with high-risk smoldering myeloma. Early results, presented at ASH 2025, suggest that all treated patients achieved very deep responses, with no detectable disease on multiple tests.

Dr. Mikhael noted that the U.S. FDA has approved daratumumab as the first monotherapy treatment for high-risk smoldering myeloma in November 2025 — “marking a major shift from watch-and-wait.”

“Studies like yours—and others bringing bispecific antibodies and CAR T-cell therapies into frontline treatment—are likely to change the field,” said Dr. Mikhael, in conclusion.

4. What Is the Future of Relapse Therapy in Myeloma?

According to Dr. Landgren, “The jury is still out. We can look at different studies.  If you use a CAR T-cell therapy for the first time, or you have a patient population that has been exposed to bispecific antibodies, and then you use that same CAR T. If those studies, say that in the first example, the duration or the CAR T-cell seem to be better, you may conclude that the CAR T-cell is preferential to start with. But there are also differences in patient populations. In the second example, those patients had to receive one more line of therapy. They went from bispecific antibody therapy to CAR T-cell therapy. We’re not comparing the same patients; it’s apples to oranges.”  

“On top of [that], if you look at the engineering of how these drugs are designed, many of them go after  the B-cell maturation antigen, but they don't just randomly grab this BCMA on the surface of myeloma cells, they bind to particular proteins,” he further noted

Dr. Landgren rationalized how drugs are designed “a little bit different.”    

“I think for simplicity, a lot of patients probably get combinations with bispecific antibodies,” he stated.

Dr. Landgren thinks that “the data is not definitive and the studies are small.”  “Until we have the proper tests to really show the mechanism of resistance, it's a lot of handwaving going on,” he said.

Dr. Mikhael agrees with Dr. Landgren, saying: “I think one of the things we're going to have to learn a lot more about is when someone relapses, what is their disease with respect to that BCMA target? As you’ve said, part of the work we do in our lab at TGen at the City of Hope is to look at how molecularly someone relapses on elranatamab versus talquetamab versus linvoseltamab, to compare it. But then we look at someone's own immune system.” 

5. Innovations in Myeloma Care: What’s Next?

Dr. Mikhael asked Dr. Landgren, “What excites you most about the recent and upcoming innovations in myeloma?”

Dr. Landgren responded that outcomes for people newly diagnosed with multiple myeloma have improved substantially. In the past, the average patient was around age 70, and expectations were more limited. Today, for patients without high-risk features or other significant health issues, he may tell them there is a high likelihood (though not a guarantee) that they could live as long as someone of the same age and sex without myeloma. He noted that this is something he would not have said 20 years ago.

Dr. Landgren emphasized that this progress reflects decades of global effort in research, drug development, and clinical care. “That is something that we together have done in the world. Everyone was pushing for this disease, pushing forward all the technologies, all the use of these drugs, and all the drug companies and the biotechs. We are still not done. We don't have a defined cure. There are patients that have disease that is more aggressive," he said.

Myeloma is still not considered curable. Some patients have more aggressive disease, often referred to as high-risk myeloma. “I'm still not sure I know how to define that. I think we need better tools to dissect this group of patients that have a worse outcome to dissect out. There is clearly not one high-risk disease. There are many high-risk diseases. We need better tools for that. And we need a new mechanism of action," he said.

Dr. Landgren also highlighted the importance of improving how the disease is measured and tracked. If forced to choose, he said he might prioritize better diagnostic and monitoring technology over developing a single new drug, because more precise tools could help determine how close patients are to a cure. At the same time, he made clear that additional drugs are still needed.

“We still need more drugs. We are working on that also, discovery-wise, trying to understand new targets. I think where the drugs are going, in the development, we will see more new targets when we have done discovery. We looked through 20,000 genes that code for surface proteins."

“We look for those surface proteins that are not expressed on normal tissue, because if you go after the wrong ones, you're going to hit all the other organs—the heart, the brain, the lungs. You want to have those that are disease specific. If you narrow that down to a set of surface markers, you could potentially target them. What is striking is to see that many of them are on every myeloma cell in every patient."

“Those are not surprisingly the CD38 BCMA, the GPRC5D, and so forth. That's what the drugs are. If you start looking in extramedullary disease, or if you're looking other compartments of disease with other markers, we need to develop drugs for those. To deliver a cure, we need to identify those markers," he noted further.  

He concluded that continued progress would depend on both better technology and new treatments. Efforts are underway to expand precision medicine approaches that tailor care to each patient’s specific disease, with the aim of moving closer to a cure.

"We have more targets coming, and it will be driven out of data. We are pushing very, very hard. I want to build a very strong precision medicine program. That’s what we’re doing at the University of Miami, where we are trying to scale this up.  We're going to push and push until we get over the goal line," he stated.

After this dialogue, Drs. Mikhael and Landgren engaged with attendees in a Q&A session.  

To take part in one of these sessions in person or virtually, be sure to visit events.myeloma.org to find an IMF Patient & Family Seminar or IMF Myeloma Community Workshop near you.