IMS and IMWG Consensus Defines Cure in Multiple Myeloma as Five Years Treatment-Free With Sustained MRD Negativity
核心洞察
Global myeloma experts presented a new consensus definition of cure at the International Myeloma Society (搜索) 23rd Annual Meeting in Glasgow, Scotland.
Under the definition, newly diagnosed or relapsed patients may be considered cured after five years in complete remission without myeloma treatment.
The criteria require at least four negative MRD assessments at 10^-6 sensitivity, including one at the five-year mark, plus negative PET/CT or diffusion-weighted whole-body MRI.
Global myeloma experts have established a consensus definition of cure for multiple myeloma (搜索), presented at the International Myeloma Society (搜索) (IMS) 23rd Annual Meeting in Glasgow, Scotland, on behalf of IMS and the International Myeloma Working Group (搜索) (IMWG). The definition sets a standard for when a long-term response can be called a cure and places sustained measurable residual disease (搜索) (MRD) negativity at the center of that assessment.
Long considered an incurable disease, multiple myeloma (搜索) is entering a phase in which some patients remain free of detectable disease for years after treatment ends. Advances in therapeutic strategies and disease-monitoring technologies are giving clinicians more effective ways to drive deep responses and more sensitive ways to measure them. As more patients achieve these outcomes, a clear standard for determining when a long-term response may be considered a cure became necessary.
The Criteria
Under the consensus definition, a patient with newly diagnosed or relapsed disease may be considered cured after five years in complete remission without any myeloma treatment. During that period, the definition requires:
- At least four negative MRD assessments, including one at the five-year mark, with no positive result in between.
- MRD tests using next-generation sequencing or next-generation flow at a sensitivity of 10⁻⁶, or one myeloma cell among one million cells.
- Advanced imaging with PET/CT or diffusion-weighted whole-body MRI showing no disease at the start and end of the period, with no positive scan in between if additional scans are performed.
These requirements place highly sensitive MRD testing at the center of determining whether deep responses in multiple myeloma (搜索) have remained durable over time.
Clinical Reaction
"In the world of treating multiple myeloma (搜索), we have now reached a point where we can actually cure patients. Part of that cure definition is that the patient has no measurable disease in their bone marrow," said Dr. Jeffrey Wolf, clinical professor, Department of Medicine, University of California, San Francisco. "The ideal way of measuring that is to use the clonoSEQ (搜索) Assay, which has been proven over many years to be the most reproducible way of defining residual disease in these patients."
Patient advocates framed the definition as a starting point rather than an endpoint. "Patients are excited to hear the cure conversation gain momentum but want to balance the hope with their lived reality," said Jenny Ahlstrom, myeloma patient and CEO and founder of the HealthTree Foundation (搜索). "Given that all myeloma is not the same, learning who can and will be cured will be one of the most important discoveries in the near future."
clonoSEQ and Guideline Alignment
Adaptive Biotechnologies said its clonoSEQ (搜索) assay is positioned to support the level of disease monitoring required under the new definition. clonoSEQ is described by the company as the first and only FDA-cleared next-generation sequencing MRD test, cleared as an in vitro diagnostic for detecting and tracking MRD in patients with multiple myeloma (搜索) or B-cell acute lymphoblastic leukemia (搜索) using bone marrow, and in chronic lymphocytic leukemia (搜索) using blood or bone marrow. It is also available in diffuse large B-cell lymphoma (搜索), mantle cell lymphoma (搜索) and other lymphoid cancers and specimen types as a CLIA-validated laboratory-developed test, and is covered by Medicare for MM, CLL, ALL, DLBCL and MCL. The assay identifies and quantifies DNA sequences in malignant cells, detecting one cancer cell in one million healthy cells, and has been studied in more than 300 peer-reviewed publications. It is CE-marked under the EU In Vitro Diagnostic Regulation.
"The consensus definition of cure in myeloma marks a defining moment for the patient community and a landmark achievement for the field. Together with last week's NCCN Guidelines update, this development clearly affirms that highly sensitive MRD assessment should be systematically integrated into routine myeloma care," said Susan Bobulsky, chief commercial officer, MRD, at Adaptive Biotechnologies. "As the first and only FDA-cleared next-generation sequencing MRD test, clonoSEQ (搜索) is uniquely positioned to support the level of rigor the cure definition requires, giving clinicians a precise way to measure deep responses over time and offering patients clearer insight into the outcome of their treatment."
Open Questions
Establishing the consensus definition is described as the beginning of a new era for patients. Significant ongoing research will be required to expand the fraction of patients who are cured and to better understand the probability of cure in specific patient subpopulations. Further research is also needed to determine which patient populations can achieve long-term treatment-free remission and to understand the likelihood of cure across different groups of multiple myeloma (搜索) patients.
Adaptive Biotechnologies said it will continue supporting the use of highly sensitive MRD testing in multiple myeloma (搜索) through its clonoSEQ (搜索) platform, and expects continued research into sustained MRD negativity and long-term treatment-free remission as the definition is incorporated into clinical research and myeloma care.