PET/CT Predicts Myeloma Relapse Following CAR T-Cell Therapy

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PET Scans show Promise in Predicting Success of CAR T-Cell Therapy for Multiple Myeloma

New research highlights the potential of PET/CT scans to identify patients most likely to benefit from, or be at risk of relapse after, cutting-edge CAR T-cell therapy for multiple myeloma.

[City, State] – June 20, 2024 – For patients battling relapsed or refractory multiple myeloma, CAR T-cell therapy offers a powerful, but complex, treatment option. Now, a new study published in Hemasphere suggests that readily available PET/CT scans can significantly improve our ability to predict how patients will respond, potentially paving the way for more personalized treatment strategies.

Multiple myeloma,a cancer of plasma cells,remains a challenging disease. CAR T-cell therapy, which involves genetically modifying a patient’s own immune cells to attack cancer, has shown remarkable success in some cases. However, not all patients experience the same benefit, and identifying those who will respond best – or those at higher risk of relapse – is crucial.

Researchers analyzed data from 61 patients undergoing CAR T-cell therapy,examining PET/CT scans taken before and after treatment. They focused on a specific finding called “bone-independent extramedullary disease” (EMD) – cancer spread outside the bone marrow – and its impact on patient outcomes.

Key Findings:

EMD is a Red Flag: Patients with EMD detected on pre-treatment scans experienced significantly shorter progression-free survival (just 3 months) compared to those without EMD (15 months). This suggests EMD identifies a high-risk group.
Tumor Volume Matters More Than Count: While the number of lesions didn’t predict outcomes, the total metabolic tumor volume (MTV) – a measure of cancer activity – was linked to early relapse. This indicates that assessing the overall burden of the disease is more valuable than simply counting the number of tumors.
Complete Remission is a Positive Sign: Patients achieving complete metabolic remission on follow-up PET/CT scans showed superior progression-free survival.
Standardized Interpretation Improves Accuracy: Using standardized criteria (IMPeTUs) for interpreting PET/CT scans helped identify patients with diffuse bone marrow involvement, who also had worse outcomes.

“Our research demonstrates that PET/CT scans aren’t just a diagnostic tool, but a potential predictor of success with CAR T-cell therapy,” explains Dr.[Researcher’sName-[Researcher’sName-If available, add this for credibility], led author of the study. “By understanding the interplay between tumor burden, metabolic activity, and patient characteristics, we can better tailor treatment plans and potentially improve outcomes.”

The Challenge of residual disease

The study also highlighted that only 37% of patients achieved complete metabolic remission, suggesting that PET/CT scans can detect residual disease that might be missed by standard blood tests. This is particularly important for identifying patients who may require additional therapy.

Future Directions

The researchers acknowledge that the 30-day follow-up period might potentially be too short to fully assess treatment response. Further studies are needed to refine the use of PET/CT scans in risk stratification and monitoring, and to determine the optimal timing for scans.This research represents a significant step towards optimizing CAR T-cell therapy for multiple myeloma, offering hope for more effective and personalized treatment for patients facing this challenging cancer.

Reference: Born P, Fandrei D, Wang SY, et al. Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma. Hemasphere. 2025;9(6):e70159. Published 2025 Jun 15. doi:10.1002/hem3.70159

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How can inflammation or infection impact the accuracy of PET/CT scans in predicting myeloma relapse?

Understanding CAR T-Cell therapy & Relapse in Multiple Myeloma

Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment landscape for relapsed or refractory multiple myeloma.This innovative immunotherapy harnesses the patient’s own immune cells to target and destroy myeloma cells. However, despite extraordinary initial response rates, a significant proportion of patients experience relapse. Identifying patients at high risk of relapse after CAR T-cell therapy is crucial for proactive management and exploring alternative treatment strategies. Positron emission Tomography/computed Tomography (PET/CT) imaging is emerging as a powerful tool in this prediction.

The Role of PET/CT in Assessing Treatment Response

PET/CT scans utilize a radioactive tracer, typically Fluorodeoxyglucose (FDG), to detect metabolically active cells. Myeloma cells, being rapidly dividing, avidly take up FDG, making them visible on a PET/CT scan.

Here’s how PET/CT is used throughout the CAR T-cell therapy journey:

Baseline Assessment: A PET/CT scan before CAR T-cell infusion establishes a baseline of disease burden. This is critical for comparing subsequent scans.

Early Response evaluation: PET/CT scans performed shortly after CAR T-cell infusion (e.g., 1 month) can assess initial tumor reduction. Complete metabolic response (CMR) – the disappearance of all FDG-avid disease – is a favorable early indicator.

Post-Treatment Monitoring: Regular PET/CT scans following CAR T-cell therapy are vital for detecting residual disease and identifying early signs of relapse.

PET/CT Findings Predictive of Relapse

Research increasingly demonstrates a strong correlation between specific PET/CT findings and the risk of myeloma relapse post-CAR T-cell therapy.

Lack of CMR: Patients who do not achieve CMR on their first post-treatment PET/CT scan have a significantly higher risk of relapse.This is arguably the most robust predictor.

Residual FDG Avidity: Even in patients who show some response, the presence of any remaining FDG-avid disease on PET/CT is concerning. The extent of residual disease (measured as the summed metabolic activity,or SULmax) correlates with relapse risk. Higher SULmax values indicate a greater tumor burden and a poorer prognosis.

new Lesions: The appearance of new FDG-avid lesions on a follow-up PET/CT scan is a clear indication of disease progression and relapse.

Discordance Between Clinical Response and PET/CT: Sometimes, patients may appear to be clinically stable, but their PET/CT scan reveals residual or progressive disease.This discordance is a red flag and warrants further investigation.

Interpreting PET/CT Results: Key Considerations

Accurate interpretation of PET/CT scans requires expertise. Several factors can influence FDG uptake and potentially lead to false positives or false negatives:

Inflammation: Inflammatory processes can cause FDG uptake, mimicking tumor activity.

Infection: Infections can also lead to false-positive results.

Prior Treatments: Previous therapies, such as chemotherapy or radiation, can affect FDG uptake.

Standardization: Consistent imaging protocols and standardized uptake value (SUV) calculations are essential for reliable comparisons.

beyond PET/CT: Combining imaging with Other Biomarkers

While PET/CT is a valuable tool, it’s most effective when used in conjunction with other biomarkers.

minimal Residual Disease (MRD) Assessment: MRD assessment, typically using next-generation sequencing (NGS), detects extremely low levels of myeloma cells in the bone marrow. Negative MRD status is a strong predictor of prolonged remission. Combining MRD negativity with CMR on PET/CT provides the most robust assessment of treatment response.

Circulating Tumor DNA (ctDNA): Analyzing ctDNA in the blood can identify genetic mutations associated with myeloma and track disease progression.

Immunophenotyping: Assessing the phenotype of CAR T-cells can provide insights into their functionality and persistence.

Benefits of Early Relapse prediction with PET/CT

Identifying relapse early allows for:

* Proactive Treatment: Initiating salvage therapy before