ABS 106: Evaluating the Prognostic Value of Circulating Tumor Cells in Immunotherapy Response for Smoldering Multiple Myeloma

Subear Hussein ¹ ² , Rosa Toenges ¹ , Jean-Baptiste Alberge ¹ , Hannah Ashton ¹ , Ankit K. Dutta ¹ , Irene M. Ghobrial ¹

¹ Dana-Farber Cancer Institute, Harvard Medical School
² Northeastern University

Van Wickle (2025) Volume 1, ABS 106

Introduction: Multiple Myeloma (MM) is a type of blood cancer that develops from early, symptomless conditions called Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). These early stages are often found by chance and currently require invasive bone marrow biopsies to monitor disease status—procedures that can be uncomfortable and difficult for patients. There is a pressing need for easier, less invasive ways to detect and track disease progression.
One promising solution is to use simple blood tests to measure circulating tumor cells (CTCs), which are cancer cells that break away from tumors and enter the bloodstream. In this study, we investigated whether CTCs could be used to monitor how SMM patients respond to treatment. We analyzed blood samples from 85 SMM patients participating in three different clinical trials testing new immunotherapies at Dana-Farber Cancer Institute.
Blood samples were processed to identify and count CTCs at different stages of treatment. Across all three trials, we observed a consistent decrease in CTCs, especially during the early treatment cycles. These decreases closely matched declines in M-spike, a standard blood marker used to measure cancer activity.
The results suggest that tracking CTCs through blood samples could be a reliable and non-invasive way to monitor how well patients are responding to treatment. This approach may reduce the need for bone marrow biopsies and could eventually help doctors tailor treatments to individual patients more effectively. Our findings highlight the potential of CTC testing to improve care for people with early-stage blood cancers.

Methods: We analyzed peripheral blood samples from 85 patients diagnosed with Smoldering Multiple Myeloma (SMM) who were enrolled in three separate immunotherapy clinical trials at Dana-Farber Cancer Institute. Blood samples were collected at multiple timepoints throughout treatment and processed using the CellSearch AUTOPREP system, which isolates circulating tumor cells (CTCs) based on specific surface markers (CD138+CD38+CD45–CD19–). The samples were then scanned using the CellSearch ANALYZER II system, and CTCs were counted using Gateworks software. These counts were compared to M-spike levels—a standard marker of disease burden—measured from clinical blood work collected at the same timepoints. This approach allowed us to track CTC levels over time and assess how they correlated with treatment response across the three immunotherapy regimens.

Results: CTC counts decreased across all three immunotherapy trials. In Immunotherapy 1, one patient’s CTCs dropped from 15,372 at baseline to 0 by Cycle 24; M-spike decreased from 0.55 to 0. In Immunotherapy 2, CTCs fell from 1,592 to 0 by Cycle 10, with M-spike decreasing from 1.24 to 0. In Immunotherapy 3, CTCs declined from 549 to 0 by Cycle 56, and M-spike dropped from 1.65 to 0.32. At Cycle 3, CTC reductions were 99.98%, 98.18%, and 80.52%, respectively, showing a rapid early decline in circulating tumor burden across therapies.

Discussion: Our findings support the use of circulating tumor cells (CTCs) as a non-invasive biomarker for monitoring treatment response in Smoldering Multiple Myeloma. The strong correlation between CTC decline and M-spike reduction across different immunotherapies suggests CTC enumeration could reduce reliance on invasive bone marrow biopsies. Early CTC trends may also help identify which patients are responding to treatment sooner. Future studies should explore CTC dynamics in larger cohorts and investigate their role in guiding personalized treatment strategies, potentially improving outcomes through more targeted and timely therapeutic decisions.