PET/CT Predicts Myeloma Relapse After CAR T-Cell Therapy
PET/CT Scans Show Promise in Predicting Outcomes for CAR T-cell Therapy in Multiple Myeloma
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Positron emission tomography/computed tomography (PET/CT) scans are emerging as a valuable tool for predicting how patients with relapsed or refractory multiple myeloma will respond to CAR T-cell therapy, according to recent research. The scans can help identify high-risk individuals and potentially optimize treatment strategies, offering a more nuanced understanding of disease progression beyond conventional markers.
The Prognostic Value of PET/CT in Multiple Myeloma
Multiple myeloma, a cancer of plasma cells, often becomes resistant to treatment over time. CAR T-cell therapy, which involves modifying a patient’s own immune cells to target the cancer, has shown significant promise in these cases. However,not all patients respond equally well. Identifying factors that predict response is crucial for personalized treatment approaches.
Researchers have been investigating the role of PET/CT scans in assessing disease burden and metabolic activity, and how these factors correlate with patient outcomes. PET/CT scans detect areas of increased metabolic activity, indicating cancer cells, and provide a visual representation of tumor distribution throughout the body.
A recent study published in Hemasphere (Born et al., 2025) directly compared PET/CT findings with other biomarkers and patient outcomes to determine its prognostic value. The findings highlight the importance of specific PET/CT features in predicting progression-free survival (PFS).
Extramedullary Disease and Metabolic tumor Volume: Key Indicators
The study revealed that patients with extramedullary disease (EMD) – myeloma that has spread outside the bone marrow - had significantly shorter progression-free survival. Specifically,those with bone-self-reliant EMD experienced a PFS of only 3 months,compared to 15 months for those without it (P = .01).This suggests that EMD is a notably unfavorable prognostic factor.
Interestingly, the number of lesions detected on PET/CT did not correlate with PFS, nor did metabolic tumor volume (MTV) - a measure of the total metabolic activity of the tumor. However, researchers found a link between high MTV and elevated levels of soluble B-cell maturation antigen (sBCMA) and interleukin-6 (IL-6), inflammatory markers often associated with more aggressive disease. Importantly, higher MTV did not negatively impact CAR T-cell expansion or bystander T-cell fitness, suggesting its predictive value lies elsewhere.
Further analysis showed that patients achieving complete metabolic remission on follow-up PET/CT scans demonstrated superior PFS. This underscores the importance of achieving a deep response, as visualized by PET/CT, for long-term disease control.
Standardizing Interpretation with IMPeTUs criteria
One challenge with PET/CT interpretation is the potential for variability between observers. To address this, the researchers incorporated the Italian Myeloma criteria for PET Use (IMPeTUs), a standardized approach to interpreting PET/CT findings. Using IMPeTUs, they found that patients with diffuse bone marrow uptake (greater than Deauville 3) had demonstrably worse outcomes.
Combining IMPeTUs-defined risk factors – EMD and bone marrow infiltration - proved highly effective in stratifying patients, allowing for the identification of those at risk of early relapse or those likely to experience extended survival.This highlights the value of a standardized, comprehensive assessment of PET/CT scans.
volumetric Assessment vs.Lesion Enumeration & Residual Disease Detection
The study also supports the idea that volumetric tumor burden assessment (MTV) is more predictive than simply counting the number of lesions. Total MTV was linked to the risk of early relapse, suggesting that the overall metabolic activity of the tumor is a more important indicator of prognosis than the sheer number of affected sites.
Only 37% of patients achieved complete metabolic remission on follow-up scans, a finding that emphasizes the utility of PET/CT in detecting residual disease that may not be apparent through traditional biochemical markers like serum free light chains.This ability to identify minimal residual disease (MRD) is critical for guiding post-treatment strategies.
Future Directions and Considerations
The authors acknowledge that their 30-day follow-up period may be too short to fully capture the nuances of treatment response and disease progression. Further studies with longer follow-up are needed to refine the use of PET/CT in patient risk stratification and monitoring.
Ultimately, integrating PET/CT findings, particularly when interpreted using standardized criteria like IMPeTUs, into clinical practice has the potential to significantly improve the management of multiple myeloma patients undergoing CAR T-cell therapy.This will allow clinicians to tailor treatment approaches, identify high-risk individuals for more intensive interventions