The Impact of Circulating Plasma Cells on Overall Survival (OS) in Patients with Newly Diagnosed Multiple Myeloma (MM) - Results of a Multicenter Study

Background: In 2021, the International Myeloma Working Group updated the diagnostic criteria for primary plasma cell leukemia to reduce the proportion of detectable circulating plasma cells (PCs) to 5%. However, studies assessing the role of circulating PCs are mostly retrospective and include a small group of patients with different induction therapy regimens. Aims: To determine the overall survival (OS) in real clinical practice in primary multiple myeloma (MM) patients on bortezomib-containing induction therapy depending on the presence and proportion of circulating PCs in the peripheral blood. Patients and Methods: From 2015 to 2018, a prospective registration study included 3,220 primary MM patients from 44 centers aged 24 to 90 years (median - 63). The stage of the disease according to the ISS system at the time of diagnosis was assessed as I in 27% of patients, II in 23%, III in 50%. All patients underwent an assessment of circulating PCs at the onset of the disease using traditional microscopy; at least 100 nucleated cells in a peripheral blood smear were analyzed. The absolute majority of patients underwent induction therapy with the inclusion of bortezomib - 98%, immunomodulatory drugs were used in 2% of cases. Autologous stem cell transplantation was performed in 304 patients. Relapse therapy was carried out using bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab, ixazomib in accordance with registration indications. The effectiveness of treatment, outcomes (relapse, progression, death), and causes of death were analyzed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10. Results: Circulating PCs were detected at the onset of the disease in 207 MM patients (6% of cases), with 1% to 4% of PCs detected in 128 cases (62%), 5% to 20% in 44 patients (21%), and more than 20% in 35 cases (17%). In 3013 patients, MM proceeded without the presence of circulating PCs at the onset of the disease. The 5-year OS of patients with MM without detection of circulating PCs at the onset was 42% versus 25% in the case of their detection (p<0.05). At the same time, the median OS was 2.2 times lower in the presence of PCs in the peripheral blood at the onset of MM and was 21 months versus 48 months in the group of patients without detection of circulating PCs. No differences were found when assessing the OS parameters depending on the proportion of circulating PCs at the onset of the disease. The median OS was 22 months with detection of 1-4% PCs in peripheral blood versus 16 months in the group of patients with 5-20% PCs circulation and 20 months with more than 20% PCs in peripheral blood (p> 0.05) Significant differences in OS were obtained when analyzing the concentration of platelets in MM patients with the presence of circulating PCs in the blood - the median OS was 24 months with a platelet count of >100,000/μl versus 12 months with detection of <100,000/μl at the onset of the disease (p<0.05). Conclusion: Detection of circulating PCs in MM patients is a factor of unfavorable prognosis regardless of their quantity - detection of 1% or more PCs in peripheral blood significantly impairs the OS indicators in patients with MM. It is advisable to revise the diagnostic criteria for primary plasma cell leukemia in the direction of reducing the proportion of circulating PCs to 1%.