From May 13–19, 2026, the 12th World Congress on Multiple Myeloma (COMy 2026) was held in Paris, France. As one of the most influential global meetings in the field of multiple myeloma (MM), the congress brought together leading experts to discuss the latest advances in translational research, novel therapeutics, and patient care.During the meeting, Professor Shaji Kumar of the Mayo Clinic delivered a forward-looking overview of the forthcoming revision of the International Myeloma Working Group (IMWG) response criteria. Based on the recent Paris Consensus discussions, the updated framework aims to address the profound changes that have occurred in MM diagnosis, monitoring, and treatment over the past decade, while providing a stronger foundation for future individualized treatment strategies.
Reshaping Biomarker Hierarchies: Mass Spectrometry Moves to the Forefront
The evolution of response assessment in multiple myeloma has always been closely linked to advances in monoclonal protein detection technologies. According to Professor Kumar, one of the most significant changes in the upcoming criteria is the redefinition of biomarker priorities.
Traditional serum protein electrophoresis (SPEP), long considered the backbone of disease monitoring, is increasingly being supplemented—and in some settings challenged—by highly sensitive mass spectrometry techniques. Compared with conventional assays, mass spectrometry offers superior specificity and sensitivity, particularly when distinguishing low-level monoclonal proteins from polyclonal background signals.
At the same time, the role of 24-hour urine protein electrophoresis has been substantially reduced. Under the new framework, urine studies will only be recommended in selected situations, such as patients with measurable urinary disease at baseline when serum free light chain assessment is not feasible.
Consequently, routine response evaluation will rely predominantly on a combination of serum protein electrophoresis and serum free light chain measurements.
This transition not only reduces the burden associated with 24-hour urine collection but also improves data completeness and consistency in both clinical practice and clinical trials. It represents a decisive move toward a serum-based monitoring strategy in modern myeloma care.
Streamlining Response Categories: Saying Goodbye to MR and sCR
As highly effective treatment strategies—including quadruplet regimens, anti-CD38 monoclonal antibodies, and BCMA-targeted therapies—have become standard, deeper responses are now routinely achieved in many patients.
Against this backdrop, several historical response categories have lost much of their practical relevance.
Professor Kumar highlighted two major simplifications in the revised criteria.
First, the category of Minimal Response (MR) will be eliminated. In contemporary practice, the vast majority of patients achieve at least a partial response, and a 25%–49% reduction in M-protein rarely influences clinical decision-making.
Second, the category of Stringent Complete Response (sCR) will also be removed.
Introduced in the 2016 criteria, sCR relied on parameters such as serum free light chain ratios and bone marrow plasma-cell assessments to define a deeper level of complete remission. However, widespread use of therapeutic antibodies has complicated interpretation of serum free light chain measurements, reducing the reliability of sCR as a meaningful endpoint.
Instead, minimal residual disease (MRD) assessment now provides a far more objective and reproducible measure of response depth.
By eliminating redundant categories, the revised framework places greater emphasis on the central clinical question: how deep a remission has truly been achieved.
Functional Imaging Becomes a Core Component of Response Assessment
Another landmark development is the formal integration of functional imaging into response evaluation.
Professor Kumar noted that traditional skeletal imaging primarily captures anatomical damage, such as osteolytic lesions, but provides limited information regarding residual disease activity after treatment.
To address this limitation, the updated criteria formally incorporate standardized functional imaging approaches.
For patients evaluated using whole-body MRI or diffusion-weighted imaging, response assessment will utilize the MY-RADS scoring system. For PET-CT, interpretation will be standardized according to the Deauville five-point scale.
This change carries major clinical implications.
In particular, assessment of extramedullary disease will now require confirmation that abnormal metabolic activity has completely resolved before a patient can be considered radiologically responsive.
Professor Kumar emphasized that follow-up imaging should ideally employ the same modality used at baseline to ensure accurate comparisons over time.
The inclusion of functional imaging represents a shift from evaluating disease burden solely through protein markers to assessing both tumor metabolism and spatial disease distribution.
Refining MRD Assessment: Moving Beyond 10⁻⁵
Minimal residual disease has emerged as one of the most powerful prognostic indicators in multiple myeloma and is increasingly recognized as a meaningful surrogate endpoint in clinical trials.
The revised criteria provide the most detailed MRD framework to date.
Professor Kumar explained that 10⁻⁵ sensitivity, determined through next-generation sequencing (NGS) or next-generation flow cytometry (NGF), will remain the standard threshold for defining MRD negativity.
However, the new recommendations strongly encourage reporting of 10⁻⁶ sensitivity whenever feasible, particularly in clinical research and advanced clinical practice settings.
More importantly, Professor Kumar introduced the concept of “deep MRD” or “ultra-refined MRD.”
This goes beyond simply lowering the detection threshold and instead defines a multidimensional remission state requiring simultaneous fulfillment of several criteria:
- MRD negativity by NGS or NGF
- Negative functional imaging
- Negative mass spectrometry assessment of monoclonal proteins
- Absence of circulating plasma cells in peripheral blood
This integrated definition provides a potential framework for future discussions surrounding operational or functional cure in multiple myeloma.
As therapies continue to improve, achieving deep MRD status may become a primary objective of next-generation treatment strategies.
Optimizing Confirmation and Progression Criteria
The revised response criteria also introduce important practical improvements for clinical trial conduct.
Historically, response categories required confirmation at two consecutive assessments, often resulting in delays and unnecessary data loss.
To address this issue, Professor Kumar described a new concept termed “same-time-point confirmation.”
Under this approach, if all required criteria for a specific response category are met simultaneously—including serum protein electrophoresis, serum free light chain measurements, and quantitative immunoglobulin assessments—the response can be assigned immediately without waiting for a subsequent evaluation.
This modification is expected to improve trial efficiency and reduce unnecessary observation periods.
Meanwhile, the definition of disease progression continues to require a 25% increase in disease markers. However, the revised framework places greater emphasis on serum-based parameters rather than urinary measurements, further reinforcing the broader transition toward serum-centered monitoring.
These adjustments reflect an effort to balance scientific rigor with real-world practicality.
Conclusion and Future Perspectives
Professor Shaji Kumar’s presentation at COMy 2026 offered a compelling preview of how response assessment in multiple myeloma is evolving.
The forthcoming criteria move the field away from labor-intensive, experience-driven evaluation models and toward a more precise, biologically informed framework built upon highly sensitive biomarkers, functional imaging, and molecular-level disease monitoring.
The key themes of the revision include:
- Prioritization of mass spectrometry and serum-based monitoring
- Elimination of outdated response categories such as MR and sCR
- Formal integration of functional imaging into response assessment
- Expansion and refinement of MRD evaluation
- Simplification of response confirmation procedures
Together, these changes provide more sensitive and clinically meaningful endpoints for therapeutic evaluation while supporting the broader shift toward response-adapted and individualized treatment strategies.
As increasingly potent therapies continue to deepen responses, the future of multiple myeloma management may no longer focus solely on disease control, but on defining and achieving durable states of minimal or even undetectable disease—bringing the field closer than ever to the possibility of long-term treatment-free remission.
