(PA-345) The Evaluation of Circulating Tumor Cells as a Prognostic Biomarker in Newly Diagnosed Light Chain (AL) Amyloidosis

Circulating tumor cells (CTCs) emerges as a prognostic biomarker in Multiple Myeloma, independent of other established markers and may refine stratification and possibly affect therapeutic decisions. However, the prognostic impact of CTCs in light chain (AL) amyloidosis remains unexplored. We prospectively evaluated the prognostic impact of the presence of CTCs in previously untreated patients with AL amyloidosis.

Methods:

The presence of CTCs was prospectively evaluated in 218 consecutive untreated patients with AL amyloidosis diagnosed and treated at the Department of Clinical Therapeutics, Athens. CTCs were assessed in peripheral blood with Next-Generation Flow (NGF) cytometry according to the Euroflow guidelines. A median number of 10 million events (range 8-12.1x10⁶) were acquired for each patient and the median limit of detection (LOD) was 2.3x10^-6 (range 2-3.1x10^-6). Event-free survival (EFS) was defined as the time between diagnosis and hematologic relapse and/or treatment change and/or death. Overall survival (OS) was considered as the time between diagnosis and death of any cause. The median follow-up period was 24 months (range 3-80 months).

Results:

CTCs were detectable in 129/218 (59%) patients with a median value of 0.00037% (range 0.0002%-11.4%). Among patients with detectable CTCs, the distribution was as follows: 27/129 patients (21%) had CTCs at the level of 10^-6, 67/129 (52%) at the level of 10^-5, 18/129 (14%) at the level of 10^-4 and 17/129 (13%) at levels ≥ 10^-3. Patients with detectable CTCs had higher iFLCs (p=0.02), NTproBNP (p=0.01), and bone marrow (BM) infiltration (p=0.05); yet, the association between CTCs and BM infiltration was modest in a linear model. Patients with a IIIa/IIIb cardiac stage had slightly higher levels of CTCs vs. those with stage Ι and/or II; in contrast, no differences were observed among patients at different renal stages. Regarding treatment, there was no association between CTC levels and depth of hematologic response at 1, 3 or 6 months or organ responses at any time-point. Nevertheless, in the log-rank analysis, the CTC increase per log scale correlated with a gradually worse outcome for both EFS and OS. Most importantly, in a multivariate Cox regression model, CTCs as a continuous variable, conferred an independent prognostic impact (p=0.011 for EFS and p< 0.001 for OS) compared to the Mayo staging system, dFLC and treatment type (containing Daratumumab or not). The optimal CTC cut-off showing the highest C-index in the multivariate Cox model was for EFS the LOD (HR: 1.44, 95% CI:1.00-2.09; p=0.04) and 10^-4 for OS (HR: 1.88, 95% CI: 0.99-3.56; p=0.03). MRD-negativity was achieved significantly more frequently in patients with undetectable CTCs (OR:1.9).

Conclusions:

CTCs can be detected in 59% of patients with AL amyloidosis using sensitive NGF. Our data demonstrate that the presence of CTCs has an independent prognostic importance and may be a new useful predictive biomarker for newly diagnosed patients with AL amyloidosis.