Characteristics, treatment outcomes, and prognostic analysis of 118 cases of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia

Abstract Background : Lymphoplasmacytic Lymphoma/Waldenström macroglobulinemia (LPL/WM) is a rare B-cell lymphoma consist of lymphocytes,lymphoplasmacytic cells, and plasma cells. Although there is a general consensus on the diagnosis and treatment of LPL/WM, there is no standard first-line therapy due to the lack of prospective randomized clinical trials. Aims This study evaluated the efficacy and safety of different regimen in treatment-naïve (TN) LPL/WM patients through the real-world retrospective analysis. Methods:We retrospectively analysied LPL/WM patients were diagnosed during October, 2014 and October, 2024 in our hospital. These patients recived CHOP or CHOP like , FC chemotherapy. BR (Bendamustine, 70-90mg/m2, d1-2, Rituximab, 375mg/m2, d0), or VD (Bortezomib 1.3mg/m2,d1,8,15, Dexamethasone, 20mg, d1,2,8,9,15,16,22,23) or BTKi (Bruton Tyrosine kinase inhibitor, Ibrutinib 140mg QD, or Zanubrutinib 160mg BID), as the first line treatment. Then we evaluated the efficacy and survial of different treatments, analyzed PFS and OS of treatment-naïve LPL/WM patients Results There were 118 patients were diagnosed with LPL/WM from October , 2014 to October, 2024. 101 eligible patients were enrolled. The median age was 64 (range, 44-85) years,72.9% patients were over 60 years old. 58.5% patients were intermediate-high risk according to IPSSWM evaluation system. Hemoglobin decreased (median,78g/L, range 23-159), and Immunoglobulin M increased (median 35.6g/L,range 19-101) significantly. 35.0% patients with increased lymphocytes (more than 50%), 43.0% patients with increased plasma cell (more than 10%), 78% patients with MYD88 L265P mutation , only 12.82% patients with CXCR4 mutation from bone marrow detection. All the patients received median 4 cycles (range 2-6) treatment. The ORR and CRR were 85% and 5%, respectively. The VGPR, PR and MRR were 20%,30% and 30%, respectively. At a median follow-up of 38 months（range 4-108), the median PFS was 50 months. The median OS not reached. 5-year PFS and OS were 37.7% and 83.7%, respectively. The subgroup analysis results indicated that target therapy, BR, VD or BTKi with prolonged PFS （P=0.01）and OS （P=0.012）compared with traditional chemotherapy. BTKi , BR with increased MRR or VGPR than VD gruop (P＜0.05), and improved 5-years PFS, 100%, 58.3% and 30.9%, respectively (P＜0.05). The patients with increased lymphocytes or splenomegaly, BR group with better MRR or VGPR than VD regimen (P＜0.05). The patients with much more plasma cells or increased IgM , VD with increased MRR than BR regimen，and transformed to OS and PFS improvement (P＜0.05). Several independent prognostic factors affecting PFS, including high risk/very high risk (R-IPSS), non-targeted therapy, elevated LDH level, bone marrow plasma cells >10%. Non-targeted therapy is an independent prognostic factor affecting OS. Conclusions Targeted therapy has a significant effect, and individualized selection is recommended for LPL/WM patients. BR is mainly recommended for patients with increased lymphocyte and splenomegaly. VD is more suitable for patients with increased plasma cell, which can reduce IgM and relieve related symptoms.