ASH 2022: Circulating Plasma Cells in Blood as a New Outcome Marker for Myeloma

Measuring circulating clonal plasma cells (CCPCs) in the blood may be a better marker to determine myeloma outcomes for a newly diagnosed myeloma patient compared to "normal" tools like staging, LDH levels and myeloma genetics, according to a recent American Society of Hematology (ASH) session.

At the session, Prashant Ramesh, MD, from Homi Bhabha National Institute in Mumbai, shared a study that included 141 newly diagnosed myeloma patients who received induction treatment that included bortezomib and did not receive a stem cell transplant. They tested the levels of circulating plasma cells found in the blood at diagnosis and then at two additional time points following the treatment (after 3 and 6 cycles) and compared that to traditional bone marrow results. 

Bone marrow biopsies are the gold standard for plasma cell detection and measurement in newly diagnosed patients and to test for Minimial Residual Disease (MRD) after treatment, but are not easy for patients to undergo. Dr. Ramesh wanted to determine if the circulating plasma cells could be measured with the same degree of accuracy and potentially replace the traditional bone marrow biopsy as part of initial and follow-up testing. 

The study team used a test called High Sensitivity Multi-Flow Cytometry with 10-13 colors to measure the level of circulating plasma cells in the blood. Plasma cells are produced in the bone marrow, but can spill out into the blood and circulate through the body.

They collected the usual bone marrow biopsy sample at diagnosis and also performed the circulating clonal plasma cell test on the blood. At diagnosis, the circulating clonal plasma cells in the blood were detected in 76.6% of patients vs. 95% of patients who had plasma cells found in the bone marrow. Interestingly, the blood-based test at diagnosis indicated who would do better following treatment. 

If newly diganosed patients had less than .01% of circulating tumor cells in their blood at diagnosis, they had a 50 month event free survival (time until relapse) compared to a 22 month event free survival.

They then performed the same test as a Minimal Residual Disease (MRD) test to see how much myeloma remained after the initial therapy. As you can see in the chart below, if patients were MRD negative at both the 3 and 6 cycle time points, they had significantly better event free survival and overall survival compared to patients who were MRD positive or were just MRD negative at one of the two time points.

When they compared that risk status to "normal" risk status measurements used in myeloma, such as LDH levels, high-risk genetic features and staging at diagnosis, the circulating clonal plasma cell test had the highest statistical significance. This means that the blood-based circulating clonal plasma cell (CCPC) test may be more helpful than traditional tests currently used to determine long-term outcomes and risk for newly diagnosed patients. 

Dr. Ramesh concluded that monitoring circulating clonal plasma cells using high-sensitivity multicolor flow cytometry is achievable and is a good monitoring and prognostic tool in the majority of multiple myeloma patients. This could significantly limit the need for several bone marrow biopsies, give the doctor and patient a better sense of how the patient will do over time and become an important and more accurate tool to "stage" myeloma patients in the future. Most importantly, these benefits will come to patients without the pain of a bone marrow biopsy.