New Myeloma Response Criteria: What's Changing in How Doctors Measure Treatment Success

Measuring how well a treatment is working is a central part of myeloma care. At the World Congress on Controversies in Multiple Myeloma (COMy) 2026, Dr. Shaji Kumar presented an updated version of the international response criteria that doctors use to evaluate treatment progress in multiple myeloma. The new criteria, finalized at a recent meeting in Paris, reflect how much both therapies and testing technology have advanced since the last update in 2016.

Why response criteria matter for people with myeloma

Response criteria are the shared rules doctors and researchers follow to decide if a treatment is working. They make it possible to compare different treatments fairly, guide therapy decisions, and offer prognostic information that matters to patients.

As Dr. Kumar explained during his talk, uniform response criteria are even more important now that the field is discussing the possibility of a cure. Deeper responses are increasingly being used to guide treatment changes.

The first response criteria was created in the late 1960s. It has been revised several times since. A large international group of myeloma experts met in Paris to incorporate new technologies that have become available over the past decade.

The tools used to measure myeloma

Unlike many other cancers, multiple myeloma produces a reliable biomarker called the monoclonal protein. It is also called the M protein or M spike. It is an abnormal antibody made by myeloma cells. Monoclonal protein can be measured in the blood or urine using several techniques:

• Serum protein electrophoresis (SPEP): SPEP is a blood test that separates and measures proteins.
• Serum-free light chain assay: This assay is a blood test that measures small antibody fragments. For around 10% to 15% of patients, electrophoresis is not useful. The serum-free light chain assay can track M protein in those patients.
• Mass spectrometry: Mass spectrometry is a newer, highly sensitive laboratory technique that can detect smaller amounts of M protein.

Another way to measure treatment success is by looking for signs of myeloma in the body. One option is to look for the myeloma cells themselves, which can be found in the bone marrow, the blood, or in areas outside the bone marrow (called “extramedullary”). A newer option is to look for pieces of DNA that the myeloma cells release into the bloodstream, called circulating tumor DNA (ctDNA). 

Modern techniques like next-generation sequencing (NGS) and flow cytometry can find very small numbers of myeloma cells. Imaging also plays a critical role, especially when extramedullary disease is present. Extramedullary disease is when myeloma cells form tumors outside the bone marrow. They can form in soft tissues or organs. 

Less reliance on 24-Hour urine collections

One of the most patient-friendly updates is the reduced use of 24-hour urine testing. This is a test where patients need to collect their urine at home for a full day. Dr. Kumar pointed out that continuing to require 24-hour urine collections can be "very tedious for patients and often lead to a lack of complete assessment in clinical trials." The new criteria prioritize SPEP and serum-free light chain testing first. The hope is that most patients will need only a couple of 24-hour urine assessments throughout one line of therapy, usually at baseline and to confirm a complete response if disease was detected in the urine at the start.

Two response categories are going away

The new criteria retire two categories that are no longer useful:

• Minor response: This was previously defined as a 25% to 49% reduction in monoclonal protein, or a 50% to 89% reduction in urine protein. This category is being removed because today's therapies regularly produce much deeper responses. Now, minimal residual disease testing is increasingly used to guide treatment.
• Stringent complete response: This was introduced in 2016 but is no longer needed. Modern immunotherapies often push free light chain levels below normal limits, and bone marrow samples are now routinely tested for minimal residual disease. This makes the older requirements unnecessary.

Dr. Kumar also emphasized that stable disease should not be used as a measure of response. Stable disease means the myeloma stayed the same. It did not get smaller, but it did not grow either. A “response” means the disease got smaller. When myeloma stays the same, it is not a response. It is also not the disease coming back.

Simultaneous confirmation replaces sequential testing

In the past, clinical trials required two sequential test results to confirm a response. This led to another medical visit. Extra medical visits not only increase the burden on the patient but also increase the possibility of missing data in research settings. The updated criteria now allow simultaneous confirmation. This means free light chain testing and SPEP show the same result at the same time. Today, this counts as confirmation, removing the need for a second assessment later.

Minimal residual disease (MRD) testing takes center stage

Minimal residual disease (MRD) testing looks for tiny amounts of myeloma cells that may remain after treatment. The new criteria keep MRD-negative status as a key target:

• MRD-negative status still requires bone marrow testing by NGS or next-generation flow cytometry at a sensitivity of 10 to the minus 5. This is fewer than one myeloma cell in 100,000. The patient must also reach immunofixation-negative status. This means complete response.
• When labs can measure even deeper, to 10 to the minus 6 or one cell in a million, especially using NGS, they are encouraged to report results at that level.

This threshold has been accepted by the FDA and other authorities as a valid endpoint for clinical trials.

A new "deep MRD" status

The updated criteria also introduce a "stringent MRD" or "deep MRD" status. This combines all available tools to confirm there is no detectable disease. It confirms MRD with: 

• No MRD by NGS.
• No signs on functional imaging.
• No monoclonal protein on mass spectrometry.
• No circulating plasma cells in the blood. 

Dr. Kumar described this as "more of aspirational." He noted it is "not something that you'll be routinely doing in the clinic, but something that hopefully will be incorporated into clinical trials" so that meaningful data accumulates over the next 5 to 10 years.

Imaging shifts toward function

The new criteria also place more emphasis on functional imaging. This looks at activity in tissues rather than measurements alone. Doctors use a standardized system for whole-body or diffusion-weighted MRI and Deauville scoring for PET scans, with imaging response categories defined by these scales. There is no VGPR (very good partial response) category for imaging-based response, and consistency matters: the same imaging technique should be used at baseline and during follow-up.

Special considerations for some subtypes

For patients with IgA or IgD myeloma, SPEP can be unreliable because of how these proteins migrate on the test. For these patients, the criteria recommend using quantitative immunoglobulin measurements. Because mass spectrometry is more sensitive than older immunofixation testing, complete response defined by immunofixation may not be reached at the same time point when mass spectrometry is used. Reports should clearly state which technique was used and at what sensitivity.

Taken together, these updates reflect both how much myeloma therapies have improved and how much the technology for measuring disease has advanced since 2016, which paints a hopeful landscape for the future.

Key takeaway

In short, the way doctors measure how well your myeloma treatment is working is getting an update. Many of the changes are good news for patients. You can expect fewer 24-hour urine collections, which have long been one of the most inconvenient parts of myeloma monitoring. 

The criteria also lean more on highly sensitive blood tests and on minimal residual disease (MRD) testing, which can detect even tiny amounts of disease and give you and your care team a clearer picture of how deeply a treatment is working. Some older response categories are being retired because today's treatments often produce much deeper responses than they did even ten years ago. And imaging is shifting toward scans that show how active the disease is, not just how big it looks. 

Together, these changes reflect real progress in myeloma care and a growing focus on what matters most to patients.