Circulating Tumor Cell Burden May Help Identify High-Risk Subset of Patients With Multiple Myeloma

Patients with ≥ 2% circulating tumor cells (CTCs) at multiple myeloma (MM) diagnosis may constitute a subgroup of patients with outcomes resembling those of primary plasma cell leukemia, indicating this measurement as useful in identifying an ultra-high-risk subset of patients with multiple myeloma, according to findings published in Annals of Medicine.

Previous research has found that CTC levels which are 5% or higher are associated with poor clinical outcomes among patients with MM and primary plasma cell leukemia. However, a 2% threshold for CTC may also be associated with a new diagnosis of a high-risk subtype of MM. Researchers conducted a real-world, cohort analysis to determine the value of a 2% CTC level.

Overall, 1,056 patients with newly diagnosed multiple myeloma patients who were treated with novel agents were included, with 10 patients having ≥5% CTCs and receiving a diagnosis of primary plasma cell leukemia. All patients’ CTC levels were assessed via morphological evaluation on peripheral blood smears, and patients were stratified by a 2% CTC threshold. Clinical outcomes were then analyzed based on CTC burden and treatment regimens, and 49 patients had ≥2% CTCs while 926 had less than 2% CTC at time of enrollment.

The median follow-up period was longer for patients with more than 2% CTCs (28 months; 95% confidence interval [CI], 24 to 53) compared to patients with <2% CTCs (26 months; 95% CI, 24 to 28). Additionally, patients who had ≥2% CTCs had a median bone marrow plasma cell percentage (BMPC%) of 54.00 (range, 10 to 93.5), while patients with 2% or less had a BMPC% of 17.50 (range, 0 to 99.9). The median CTC percentage among patients who had 2% or less was 0 (range, 0 to 1), while the median CTC percentage for patients with ≥2% was 3 (range, 2 to 12).

The median progression-free survival (PFS) for patients with ≥2% CTCs was lower (25 months, 95% CI, 16 to 29) compared to patients with less than 2% CTCs (49 months; 95% CI, 45 to not reached). At 5 years, the PFS was higher among patients with <2% CTCs compared to patients with ≥2% CTCs (44.2%; 95% CI, 37.7 to 51.9 vs 16.6%; 95% CI, 6.7 to 41.1).

In terms of survival, the median overall survival (OS) rate was also lower for patients with more than 2% CTCs (28 months; 95% CI, 28 months to not reached) compared to patients with less than 2% CTCs (not reached; 95% CI, 64 months to not reached). The OS at 5 years was higher for patients with less than 2% CTCS (57.6%, 95% CI, 51.2 to 64.8) compared with patients who had 2% CTC or more (34.4%; 95% CI, 18.6 to 63.3%).

Patients with ≥2% CTCs who received autologous stem cell transplantation (ASCT) had only a slight difference in PFS compared to patients without ASCT (23 months; 95% CI, 20 to not reached vs 25 months; 95% CI, 14 to 29; P= 0.32).

Among patients with <2% CTCs, 1 high-risk cytogenetic abnormality (HRA) adversely impacted prognosis (PFS, 34 months; 95% CI, 29 to 46 vs 58 months; 95% CI, 47 to not reached), while in the ≥2% CTC group, ≥2 HRAs were associated with significantly worse outcomes (25 months; 95% CI, 29 to 36).

Patients with de novo extramedullary extraosseous (EME) myeloma and who had ≥2% CTCs had a lower OS compared to patients with de novo EME with 2% or less CTCs (11 months; 95% CI, 8 to not reached vs 45 months; 95% CI, 26 to 56; P= .002).

"Our study suggests that a ≥ 2% CTC threshold may help identify an ultra-high-risk subset within multiple myeloma, highlighting the potential need for distinct treatment strategies and further investigation for this population," the researchers concluded.

“Further research should continue to explore this specific aspect in greater depth,” they added.

Source:

Liang D, Yan Y, Bai S, et al. Clinical outcome of ≥2% circulating tumor cells in newly diagnosed multiple myeloma: insights from a multicenter study. Annals of Medicine. Published online April 30, 2025. doi: 10.1080/07853890.2025.2496796