P1111: waldenström macroglobulinemia in the very elderly (≥75-year-old): description of clinical features and survival outcomes in a case series from an italian academic center

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Waldenström macroglobulinemia (WM) is a rare low-grade non-Hodgkin lymphoma that affects the elderly age, when comorbidities are common. There is a paucity of data about survival outcomes, causes of death and disease features in WM patients ≥ 75-year-old at diagnosis. Previous reports have suggested inferior cause-specific survival for this older subgroup, while other studies have demonstrated higher mortality rate due to WM-unrelated conditions. Recently, an “inflammatory” variant of WM has been described, characterized by alterations in the tumor microenvironment and elevated C-reactive protein (CRP) levels not justified by other causes. Clinical and biological features and survival outcomes appear to be worse in this variant. Whether very elderly patients are more affected by the inflammatory WM type, and which is their prevalent cause of death are open questions. Aims: In this retrospective monocentric study, we aimed at describing clinical and biological features, including those related to inflammation, of two age-stratified subgroups of WM patients (≥/<75-year-old). We next evaluated the impact of associated variables on OS and EFS outcomes in the older subgroup. Methods: Our database was composed by WM patients diagnosed between 1990 and 2022 (n=165, of which 153 evaluable) at the Hematology Unit of Padua University Hospital, Padua, Italy. We compared two subgroups according to age at diagnosis (≥ 75 versus < 75-year-old, n=33 versus n=120) for WM-related characteristics, major comorbidities and therapy received. Continuous and categorical variables were compared with U-Mann-Whitney and Chi-Square test, respectively. Survival outcomes considered for age subgroups were overall survival (OS) and event free survival (EFS), defined as the time from diagnosis to death from any cause and time from start of first line therapy to start of second line-therapy or death from any cause, respectively. In the ≥ 75-year-old subgroup the impact of variables on survival outcomes were assessed by Cox-regression test, in univariate model. Results: The very elderly subgroup displayed a higher frequency of renal dysfunction (p=0.05), a trend towards being affected from other malignancies (p=0.06) and higher median values of monoclonal component (p=0.06), higher b2-microglobulin levels (p=0.04) and cytogenetic aberrations frequency (p=0.0006) with lower median values of albumin (p=0.02). No differences were observed in terms of first-line therapy regimens adopted and in terms of responses. The very elderly subgroup (Figure 1) displayed an inferior median EFS (not reached versus 166 months, p=0.02) and OS (79 versus 198 months, p=0.008). In univariate analysis we found no specific characteristics determining an inferior OS outcome in the very elderly; at variance, a worse EFS seemed to be associated with neuropathy (p=0.03), wild type MYD88 (p=0.03) and elevated b2-microglobulin (p=0.02). Interestingly, the very elderly subgroup was characterized also by a trend towards having lower levels of serum albumin (p=0.09) and elevated CRP blood concentrations (p=0.06). Summary/Conclusion: The higher incidence of second malignancies in the older subgroup could be related to inferior OS. However, we have registered no WM-related or unrelated (including “other neoplasia”) features determining a worse OS outcome. Probably, the main causes of death in the very elderly subgroup of WM patients are due to comorbidities not included in our analysis. Nevertheless, our study suggests that inflammation-related WM features (CRP, albumin, neuropathy) may impact on EFS in very elderly WM patients. Figure 1: Curves representing OS and EFS of two WM subgroups (≥/ < 75-year-old at diagnosis)Keywords: Elderly, Waldenstrom’s macroglobulinemia, Indolent non-Hodgkin’s lymphoma, Lymphoplasmacytic lymphoma