Abstract
Introduction: WM is defined as lymphoplasmacytic lymphoma (LPL) with bone marrow involvement and an IgM monoclonal paraprotein but does not require the quantification of IgM. Most WM patients present with elevated IgM. However, there is no clear definition and further study of these patients with low IgM levels.
According to the current efficacy evaluation criteria, serum IgM quantitation reduces ≥90% from baseline could be classified as very good partial response (VGPR), and ≥50% as partial response (PR). When the patients have a low IgM level, within twice of the upper limit of normal value, it is not possible to make an accurate assessment of PR or VGPR. In multiple myeloma (MM), newly diagnosed MM patients are classified into measurable and unmeasurable diseases according to the secretory status of monoclonal immunoglobulin. In previous studies, the concept of oligosecretory MM is defined due to the sensitivity of electrophoresis assays. Similarly, in WM study, when the IgM level is low, it was also impossible to accurately evaluate the efficacy of WM patients, we thus define patients with initial IgM status within twice the upper limit of normal as "oligosecretory WM patients” and twice higher than the upper limit of normal as "measurable WM patients".
Methods: The database of the Chinese Registration Network for Waldenstrom Macroglobulinemia (CRNWM) included 1274 newly diagnosed WM patients between July 2003 and September 2020 in thirty-three hematologic centers in China. We combined marrow biopsy, extramedullary disease, and clinical manifestations for oligosecretory WM patients to make a comprehensive judgment. When the tumor cells of bone marrow biopsy (BMB) declined by more than 50% accompanied by the reduction of spleen volume and lymph node size and improvement in clinical symptoms, we uniformly designated it as PR/VGPR. And complete remission (CR) was the same as before.
Results: Among the 1274 WM patients, eighty patients (6.3%) were classified as oligosecretory WM according to our definition. The clinical characteristics of oligosecretory WM and measurable WM were described in Table 1. Compared with measurable WM group, oligosecretory WM patients had a higher proportion of thrombocytopenia (41.2% vs 27.4%, P=0.008) and a lower proportion of hypoalbuminemia (32.9% vs 64.6%, P<0.001) as well as elevated serum β2-microglobulin (57.1% vs 73.8%, P=0.002).
We identified four dimensions to evaluate the patient's tumor burden: flow cytometry (FCM) of bone marrow, bone marrow biopsy (BMB), splenomegaly, and lymphadenopathy (Table 2). Overall, no significant difference was observed in median malignant cells of bone marrow by FCM (9.85% vs 8.96; P=0.0114), the percentage of abnormal cells by BMB of different ratio ranges, and patients with splenomegaly (38.4% vs 35.2%; P=0.583) and lymphadenopathy (44.8% vs 39.1%; P=0.390) (Table 2, Figure 1). However, oligosecretory WM patients had a significantly higher percentage of patients with greater than 50% abnormal cells compared to the measurable WM patients (22.7% vs 12.4%; P=0.048), suggesting some patients with low IgM levels still had high tumor infiltration of bone marrow (Figure 2).
The proportion of patients with no indication of treatment was significantly higher in oligosecretory WM group than in measurable WM group (6.1% vs 1.0%; P=0.024). And all other treatment regimens were not significantly different between the two groups. The proportion of patients who achieved CR was significantly higher in oligosecretory WM group than in measurable WM group (14.7% vs 5.4%, P=0.0043).
According to our comprehensive efficacy evaluation, oligosecretory WM patients with different treatment responses experienced significantly different values for PFS (P=0.0085). Until the follow-up deadline, five patients achieved CR and no one developed disease progression. Importantly, oligosecretory WM patients had a significantly better survival outcome. Patients with measurable disease and oligosecretory WM had a 3-year PFS rate of 59.6% and 78.8% (P=0.0013) and a 3-year OS rate of 83.4% and 87.3% (P=0.89) respectively (Figure 4).
Conclusions: Herein, we characterize a cohort of WM patients with low IgM levels. The oligosecretory WM was a special type of WM, and the patients exhibited excellent treatment response and outcomes.
Disclosures
No relevant conflicts of interest to declare.
