Are We Ready for the Cure Conversation in Multiple Myeloma?

A patient advocate's perspective on the new IMS/IMWG definition of cure

Last week at the International Myeloma Society (IMS) 23rd Annual Meeting in Glasgow, Scotland, Dr. Nikhil Munshi of Dana-Farber Cancer Institute shared an update on a consensus definition of cure for multiple myeloma, developed by the IMS and the International Myeloma Working Group (IMWG).

It was a privilege for me to chair a morning session at the IMS conference entitled “Are We Ready to Talk About Cure in Multiple Myeloma?” to hear the expert and patient perspective during the conference. 

As a myeloma patient and advocate, I've been thinking a lot about what this means, not just for the science, but for the people living with this disease.

What is the new definition of cure?

Under the new consensus definition, a patient with newly diagnosed or relapsed myeloma may be considered cured after five years in complete remission without any myeloma treatment. The five-year clock starts when treatment ends, no matter how long the patient was disease-free while still on therapy. During those five years:

• At least four MRD tests must be negative, including one at the five-year mark, with no positive results in between. Tests must use next-generation sequencing (NGS) or next-generation flow sensitive at 10-6, enough to find one myeloma cell among one million cells.

• Advanced imaging (PET/CT or diffusion-weighted whole-body MRI) must show no disease at the start and end of the five years, with no positive scans in between.

At the heart of the definition is that the patient must be off treatment. While patients can have their myeloma stay in check by using ongoing drugs, this is not part of the official cure definition. The five-year window reflects data showing that relapse becomes much less likely after five years off treatment, although late relapse is still possible.

Watch: Learn more about how the IMS and IMWG developed the new definition of cure, and what each of the criteria means.

It's wonderful to hear the word "cure"

When I was diagnosed, "cure" was a word that got mocked in myeloma circles. It was naive at best, and false hope at worst. We were told myeloma was "treatable but not curable," and that was the end of the conversation. 

So, hearing the world's leading myeloma experts formally define "cure" is a big deal. It didn't happen by accident. It happened because of years of research, clinical trials, and patients willing to participate. Here are a few examples of how far we've come:

CD38 monoclonal antibodies

Daratumumab and isatuximab are now part of frontline "quad" regimens, driving deeper responses and higher rates of MRD negativity than we've ever seen at diagnosis.

Bispecific antibodies 

Drugs like teclistamab, elranatamab, talquetamab, and linvoseltamab redirect a patient's own T-cells to attack myeloma, giving new options to people with heavily pre-treated disease. When teclistamab was combined with daratumumab in the data is among the most impressive in myeloma, ever. 

CAR T-cell therapy 

Perhaps the most striking data: in one study (CARTITUDE-2) cited at IMS, 50% of patients were alive and progression-free at least five years after a single CAR T infusion, with no maintenance therapy.

CELMoDs 

Next-generation cereblon E3 ligase modulators like iberdomide and mezigdomide build on the immunomodulatory drugs (lenalidomide, pomalidomide) that transformed myeloma care, with iberdomide now FDA-approved and both showing strong activity in clinical trials, including in patients whose disease no longer responds to older IMiDs.

Watch: Joshua Richter, MD of Mount Sinai explains why experts are starting to talk about cure. he believes cure is within reach.

What is a "cure fraction," and why does it matter?

Almost every myeloma research paper opens with the same sentence: "Multiple myeloma is an incurable disease." It has been repeated so often that it's treated as fact. But that sentence may no longer be true for some patients, and the idea of a cure fraction is one of the main reasons.

A cure fraction is the percentage of patients in a group whose disease never comes back after treatment. When researchers follow patients for many years, most people's survival curves keep dropping over time as relapses happen. For some patients, though, the curve eventually flattens into a plateau. Those patients stay in remission year after year, and their risk of relapse drops to a very low level. That plateau is the cure fraction.

According to Dr. Munshi, long-term studies estimate that between 5% and 30% of patients may already have been cured, depending on treatment, age, and disease risk. What's remarkable is that these estimates come from patients treated with older therapies, some more than a decade old. Those patients didn't have the quadruplet regimens, bispecific antibodies, or CAR-T therapies available today, so it’s likely this percentage is actually higher.

We've seen this trend at earlier meetings too. At a previous IMS meeting, data from the University of Arkansas Total Therapy protocol showed an average cure rate of 16.4% across all patients, rising as newer therapies became available and reaching 31.3% for patients treated between 2009 and 2013. Dr. Faith Davies of NYU noted that older studies showed a cure fraction around 10% to 15%, while more recent studies are in the 30% range.

This is why the cure fraction matters: if older therapies already cured a meaningful share of patients, today's therapies should cure more. Researchers are now asking how to grow that fraction. The new IMS/IMWG definition gives them a consistent way to measure it. It also means it's time for the research community to retire the automatic "incurable" opening line. A more accurate statement might be: "Multiple myeloma is curable in a subset of patients, and that subset is growing."

Understanding sustained MRD negativity

To understand the new cure definition, you need to understand MRD. MRD stands for measurable (also called minimal) residual disease. MRD testing looks for myeloma cells left in the bone marrow after treatment. These tests are very sensitive and find cells at levels far too small for standard blood tests to detect. Next-generation sequencing and next-generation flow can find one myeloma cell among 100,000 to one million healthy cells. When no myeloma cells are found at that level, a patient is considered MRD negative.

MRD negativity is one of the strongest predictors we have of long, deep remissions. But a single MRD-negative result is only a snapshot. It tells you what was found in one bone marrow sample on one day. Myeloma can be patchy in the bone marrow, and it can also hide outside the bone marrow, which is why imaging matters too.

That's where sustained MRD negativity comes in. Under IMWG response criteria, sustained MRD negativity means staying MRD negative, in the bone marrow and on imaging, on tests at least one year apart. One negative test is a snapshot; repeated negative tests over time show a trend. Patients who stay MRD negative over time generally do better than those who reach MRD negativity only briefly.

Sustained MRD negativity is also opening the door to stopping treatment. In the MASTER trial, patients who reached "MRD-SURE" status stopped treatment. At a median follow-up of 24.8 months, 79% remained off therapy with no detectable myeloma. Studies like this are part of why researchers are now designing trials with a defined treatment period rather than treatment forever. 

How sustained MRD negativity fits the cure definition

The new IMS/IMWG cure definition is essentially sustained MRD negativity off treatment, measured over five years. This distinction matters for patients:

• Sustained MRD negativity on treatment is an excellent result. It means your therapy is working deeply and durably. But it is not a cure, because we don't yet know what happens when treatment stops.

• Sustained MRD negativity off treatment for five years is what the new definition calls a cure.

Talk to your doctor: If you haven't had MRD testing, ask whether it's right for you and which test your center uses. If you have, ask how your results are trending and whether your MRD status could affect decisions about continuing or stopping treatment. Tracking your MRD results over time in HealthTree Cure Hub can help you and your care team see the trend.

Watch: Hear Mohamad Mohty, MD’s perspective on the use of MRD in defining cure and why physicians are now talking about cure in myeloma. He also discusses our next topic at the end of the video about the term “functional cure.” 

It's time to retire the term "functional cure"

If we're going to start talking about a real cure, we need to stop using the term "functional cure."

For patients, cure is binary. Either:

1. You're off therapy and your myeloma isn't coming back, or

2. You're still on treatment with a long-term, durable response.

Both are wonderful outcomes. But they are not the same thing, and only the first is a cure. The new IMS/IMWG definition makes that distinction clear by requiring five years off treatment.

"Functional cure" has typically been used by physicians and researchers to describe patients who may still have detectable myeloma cells but aren't progressing, or who live a normal life expectancy with ongoing, limited treatment. That's a great result, and it deserves a name. But here's the problem: patients don't hear the first word. They hear "cure." Then, when they learn they still need treatment or that their disease could return, it can feel like a bait and switch.

So call it something different: long-term disease control, or durable remission. But let's stop using "functional cure" and reserve the word cure for what the new definition describes.

We need caution when talking to patients about cure

Talking about curing myeloma is exciting, but I also want to urge caution, especially for doctors, researchers, and advocates talking directly with patients.

Myeloma is not a single disease. It's many diseases with different genetic features, risk levels, and responses to treatment. And right now, we can't predict at diagnosis who will be cured. A newly diagnosed patient hearing "cure" may assume it applies to them, and that's not something anyone can promise yet.

I'll share my own situation. After receiving CAR T-cell therapy, I'm one month away from another bone marrow biopsy. If I'm MRD negative, I will technically meet the new criteria for cure. That biopsy isn't just one more test. It's the result that will tell me whether my string of negative results holds, and whether I cross the line from "sustained MRD negative" to "cured."

You'd think I'd be thrilled. But myeloma is a head game. After my initial tandem transplants I became MRD negative, but I relapsed at five years. Five years is exactly the milestone this definition relies on. So being told I'm suddenly "cured" is something I'm genuinely wary of saying about myself. 

That's the emotional reality for many long-term survivors. We've learned to live with scan anxiety, lab anxiety, and the quiet question of "when," not "if." A definition on paper doesn't erase that overnight. Patients will need time, support, more data and honest conversations with their care teams about what each result does and doesn't mean.

There are also many patients who have long-term durable response being on small amounts of therapy.

What about quality of life?

Any conversation about cure has to include quality of life. For patients, being alive and in remission isn't enough if the treatment that got us there leaves us exhausted, in pain, or unable to live normally. A terrible quality of life does not equal a cure, no matter what the MRD test says.

We know this because patients have told us. In 2022, HealthTree partnered with myeloma specialists at Huntsman Cancer Institute at the University of Utah, including Dr. Ghulam Rehman Mohyuddin and Dr. Douglas Sborov, on the first study to ask myeloma patients directly what cure means to them. Patients were surveyed online and asked to rate scenarios involving side effects, disease status, and being on or off treatment on a scale of 1 to 5, with 5 representing an ideal cure. More than 1,500 patients responded, and the results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and published in The Lancet Haematology. 

What did patients say?

• Three out of four patients rated permanently stopping treatment with no evidence of disease as the ideal definition of cure. 

• Side effects and being on treatment had a major impact on whether patients considered a scenario a cure. 

• Most patients had never heard of the terms "functional cure" or "operational cure." 

That last finding is exactly why "functional cure" needs to go. Most patients don't even know what it means, and when they hear it, they hear "cure."

It's encouraging that the new IMS/IMWG definition lines up with what patients told us four years ago: off treatment, no evidence of disease. Patient voices were part of the conversation at the IMS Cure Summit too, where Dr. Vania Hungria stressed that the patient definition of cure is not the same as the physician's, and that patients value returning to normal life, free from constant uncertainty. But the formal definition doesn't measure how patients feel, and that's where we still 

What comes next: Predicting outcomes

The new definition gives researchers a common standard to measure cure and design trials with curative intent, including treatment for a fixed period rather than indefinitely. That's progress for all of us. But it's also our starting point, not the finish line. We need longer follow-up on today's therapies, better ways to predict who will be cured, and patient-reported outcomes built into how cure is measured.

At the conference, Dr. Avigan of Mount Sinai shared how his team is working to answer one of the biggest questions in myeloma: who will relapse, and who won't?

In a study of 430 patients, his team found that three factors helped predict who stayed in remission over five years:

• Standard-risk myeloma (rather than high-risk)

• Earlier-stage disease at diagnosis (such as Stage I rather than Stage III)

• The deepest MRD responses to treatment

Patients who had all three were very unlikely to relapse. Only 3% of patients in this lower-risk group relapsed during the five-year period.

Just as important, lower-risk patients who stopped therapy after two years had similar outcomes to those who kept going. That's encouraging news for patients hoping for time-limited treatment rather than therapy that continues indefinitely.

High-risk patients, however, may need to stay on treatment longer to achieve a durable remission. It's another reminder that myeloma isn't one disease, and that cure may look different depending on your risk profile.

Watch: Dr. Zachary Avigan discusses the prediction and risk stratification of patients when using the cure definition.

Key Takeaways

• The IMS and IMWG now define myeloma cure as five years in complete remission off all treatment, confirmed by at least four negative high-sensitivity MRD tests and clear advanced imaging.

• The word "cure" is finally being taken seriously, thanks to CELMoDs, CD38 antibodies, bispecifics, and CAR T.

• Long-term studies suggest 5% to 30% of patients may already have been cured on older therapies. This "cure fraction" should grow with today's treatments, and "incurable" may no longer be accurate.

• Sustained MRD negativity means staying MRD negative on repeated tests at least a year apart. On treatment, it's a strong sign of durable remission. Off treatment for five years, it's the foundation of the new cure definition.

• We still can't predict who will be cured at diagnosis, and long-term survivors may need emotional support in processing what "cured" means.

• "Functional cure" should be retired. For patients, cure means off therapy with myeloma that isn't coming back.

• Quality of life matters. In HealthTree's 2022 study with Huntsman Cancer Institute, 75% of more than 1,500 patients said the ideal cure is being off treatment permanently with no evidence of disease, and most had never heard the term "functional cure."