For myeloma patients, the word “cure” holds immense significance—it’s like the elusive pot of gold at the end of the rainbow, often feeling like a mirage that fades as you approach. This is why it’s essential to have a clear understanding of what “cure” truly means and how close we are to achieving this much-desired goal for all myeloma patients.
The Basics
To be considered cured, there must be no active myeloma, and survival rates should match those of individuals with the same age, gender, and co-morbidities. Additionally, quality of life (QoL) should be within the range of very good to excellent.
Key Questions
When striving for a cure, a few critical questions need to be addressed:
- Is there zero residual myeloma?
Advanced testing is necessary to detect whether any myeloma remains in the body. Patients who are minimal residual disease (MRD) negative in the bone marrow, and show no disease through blood tests and imaging (such as whole-body PET/CT), may be on the path to a cure. - Is myeloma permanently gone?
Even if no myeloma is detected, is it gone for good? This remains a major uncertainty in 2024. We often rely on factors such as age, early disease treatment, genetic markers, and deep responses to predict long-term remission. AI-driven algorithms could improve our ability to predict long-term outcomes, but for now, it remains a challenge.
Reality Check
Studies on long-term survivors (20 years or more) have shown that the bone marrow microenvironment often remains abnormal, meaning the conditions that allowed myeloma to grow initially are still present. Even in patients with long survival, tiny residual pockets of myeloma may persist, particularly in areas of the original, more bulky disease. This is similar to what we see in patients with post-treatment MGUS, where small residual disease pockets can remain.
Functional Cure: A Practical Definition
For patients, the difference between being MRD negative and having tiny amounts of inactive residual disease is minimal, as long as the disease isn’t growing or affecting quality of life. MRD negativity does lead to longer survival, but functional cure—which includes patients with or without small amounts of inactive myeloma—is an achievable goal. Crucially, this goal must be pursued without causing major toxicities.
Many patients are already achieving functional cure, and late relapses can often be managed with the newer, highly effective therapies available today.
Functional Cure by the Numbers
In a 2018 IMWG analysis, a “cure fraction” of 14.37% was observed, representing the percentage of patients still alive at 20 years. This serves as a baseline for evaluating the impact of newer treatments, including immunotherapies.
The GEM-CESAR Cure Trial reported around 40% MRD negativity at six years, while the ASCENT Cure Trial achieved an 84% MRD negativity rate at three years. These results suggest significant improvements in the potential functional cure rate in the years ahead.
Recent frontline therapies, such as those from the PERSEUS and IsKia trials, are also showing high early MRD negativity rates, signaling further progress toward long-term survival.
In 2024, an increasing number of patients are achieving first remissions of around five years or more, and overall survival rates of 10 years or longer. This indicates that functional cure may already be occurring for many patients.
The Focus on Long-Term Survival
For myeloma patients, the priority should shift toward long-term survival with excellent quality of life, knowing that new and exciting therapies continue to emerge. A long, productive life is becoming increasingly attainable for many, and the goal of a true cure, while still elusive, seems more achievable than ever.
The Bottom Line
The once seemingly unattainable “cure” for multiple myeloma is starting to materialize. While the journey may still be long, the mirage is turning into a real oasis, offering hope for those seeking rest and recovery along the way.
