P941: serum cxcl13 level aids in disease remission evaluation and prognosis prediction in waldenström macroglobulinemia

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Waldenström macroglobulinemia (WM) is a indolent B-cell lymphoma secreting IgM. CXCL13 is a chemokine expressed in the lymphoid tissue and is required for B lymphocyte. Studies have found elevated levels of CXCL13 in the serum and bone marrow of WM patients. Aims: To explore the value of elevated CXCL13 levels in the treatment response and prognosis evaluation of Waldenström macroglobulinemia (WM). Methods: Serum samples and clinical statistics of symptomatic WM patients were collected. Serum CXCL13 levels at baseline (0 month) and after six 6 months of treatments were measured by enzyme-linked immunosorbent assay. High CXCL13 levels were defined as higher than 2000pg/ml at baseline or higher than 200pg/ml at the 6th month. Treatment responses and overall survival were evaluated corresponding to different serum CXCL13 levels. The median follow-up period was 40 months. Results: Seventy-two patients diagnosed with WM were included in our study. The male-to female ratio was 48:24. The median age at baseline was 63 (39~81) years old. Indications for therapy included fatigue, B-symptoms, organ enlargement, anemia and IgM-related clinical complications. Sixty-nine patients received systemic therapy, including 16 patients treated with chemotherapy, 24 patients treated with rituximab combined with chemotherapy, 9 patients treated with bortezomib-based regimens, and 19 patients treated with BTK inhibitors. Three patients were not treated because of patients will. The median serum level of CXCL13 of all patients was 947 (range 10.0-21389.9) pg/ml at baseline and significantly decreased to 133.8 (range 0.0-6742.0) pg/ml after 6 months of treatments. Thirty-nine patients achieved partial remission or very good partial remission (PR/VGPR) at 6th month, and 30 patients achieved minimal remission or stable disease (MR/SD). The medium serum CXCL13 level at 6th month in PR/VGPR patients was lower than in MR/SD patients (70.2pg/ml vs 345.0pg/ml, p=0.002) (Figure 1). In chemotherapy group, patients achieved PR/VGPR had lower serum CXCL13 levels at baseline (588.4pg/ml vs 2574.0pg/ml, p=0.03). In chemotherapy group or combined with rituximab, serum CXCL13 decreased significantly in both PR/VGPR group and SD/MR group (p<0.005). In patients treated with bortezomib-based regimen or BTK inhibitors, the decrease of serum CXCL13 levels were not significant in SD/MR patients. Eight patients died in the follow-up period. The overall survival (OS) also differed corresponding to serum CXCL13 levels. Grouped by serum CXCL13 levels at baseline, the median OS was 60.0 months in patients with high CXCL13 levels, while was not reached in patients with low CXCL13 levels (p=0.0004). As for CXCL13 levels as 6th month, the median OS was 74.0 months and not reached, respectively in patients with high and low CXCL13 levels (p=0.0001). However, the survival predictive value of CXCL13 level was weakened in treatment subgroups. We further analyzed the serum CXCL13 levels in a series of 16 patients who received Orelabrutinib (BTKi). The CXCL13 levels decreased during the follow-up and most of them (12/16, 75%) were less than 10% of baseline after twelve months of BTKi treatment. Summary/Conclusion: Serum CXCL13 level decreased in WM patients treated with different regimen, and was parallel to the disease remission. Detection of serum CXCL13 at baseline or during the treatment may be helpful in evaluating treatment response and predicting prognosis.Keywords: Waldenstrom’s macroglobulinemia