LP-11. Decreased concentration of circulating BCMA protein after autologous transplantation of hematopoietic stem cells in multiple myeloma patients

Summary

B-cell maturation antigen (BCMA, CD269) is a transmembrane signaling protein preferentially expressed by mature B lymphocytes. It participates in B cell maturation and development of immune response. This cluster of differentiation is overexpressed on malignant plasma cells. The surface domain of BCMA is lysed by enzymes. It circulates in bloodstream and can be detected in blood serum of multiple myeloma (MM) patients by enzyme immunoassay (ELISA). This protein is detected at high concentrations in MM patients, both at the onset and during progression of the disease. To date, a number of studies have been published which demonstrate a relationship between the concentration of BCMA in the blood and the depth of clinical response. Our aim was to evaluate the dynamics of BCMA protein concentration in blood serum of MM patients at the debut of the disease, and on day 100 after autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials and methods

The prospective study included 26 MM patients (13 women, 13 males) aged 26 to 67 years (median, 54) with newly diagnosed MM. The diagnosis was based on the criteria of International Multiple Myeloma Working Group (IMWG) 2014. The stage of disease at diagnosis (by the R-ISS scale) was assessed as I in 8 patients; II, in 11; III, in 7 cases. 22 patients underwent induction therapy including 2 targeted drugs (bortezomib and lenalidomide); 3 patients received 3 targeted drugs (bortezomib, lenalidomide, daratumumab); 1 patient was treated by one targeted drug (bortezomib). Complete remission (CR) and very good partial remission (VGPR) were achieved in 13 patients (50%); partial remission (PR), in 13 (50%) after induction therapy. All patients underwent auto-HSCT after conditioning with high-dose melphalan (140-200 mg/m²). The serum concentration of BCMA was assessed by ELISA at the onset of the disease and after auto-HSCT on 100^th day. Blood serum samples of 15 donors were used as controls. The median concentration of BCMA protein in donors was 157.9 pg/mL (30.8 to 322.3). Statistical processing of the obtained data was carried out using SPSS software.

Results

The concentration of BCMA protein in MM patients at the onset of the disease varied from 181.4 pg/ml to 16312.8 pg/ml. In 6 patients (24%), Meanwhile, the initial BCMA concentrations did not exceed the donor values in six MM cases. Eleven patients (42%) achieved CR; 8 (31%), VGPR; 6 (23%), PR. One patient developed the disease progression (PD) on the day +100 after auto-HSCT. BCMA concentration ranged from 22.1 pg/mL to 3378.8 pg/mL. 24 patients (92%) showed a decrease of serum BCMA concentration to the donor values. BCMA concentration remained elevated in 2 cases (8%). The BCMA level was 1147.4 pg/mL in one patient with PR. Another patient had a PD with BCMA concentration of 3378.8 pg/mL. Next, we evaluated the depth of clinical response after auto-HSCT depending on the initial BCMA levels. The median BCMA concentration at the onset of MM was significantly lower in those patients who achieved CR on day +100 following auto-HSCT compared to the patients with VGPR and PR: 1252.9 pg/mL vs 2539.3 pg/mL, respectively (p =0.04).

Conclusions

76% patients with newly diagnosed MM have an increased BCMA concentration in blood serum. A complete response after auto-HSCT was accompanied by a decrease in BCMA concentration to the normal donor values in 92% of MM patients. Monitoring of BCMA concentration in blood may be considered an additional method to assess the efficiency of treatment.

Keywords

Multiple myeloma, hematopoietic stem cell transplantation, autologous, BCMA.