Health‐related quality of life in Waldenstrom Macroglobulinemia and IgM‐related disorders: A single institution experience

Waldenström macroglobulinemia (WM) is a rare disorder characterized by a serum IgM paraprotein and bone-marrow (BM) infiltration by lymphoplasmacytic lymphoma (LPL). Its clinical course is extremely heterogeneous. Observation is indicated for asymptomatic patients while treatment should be considered for symptomatic disease. WM may be preceded by previous IgM monoclonal gammopathy of undetermined significance (IgM-MGUS) consisting of the presence of IgM monoclonal component (MC) without LPL. In patients with IgM-MGUS, the risk of developing any lymphoid neoplasm is 16-fold higher than in the general population. The probability of progression is estimated at 1.5%/year with increased risk even 20 years after diagnosis. “IgM-related disorders” (IgM-RD) identifies symptoms attributable to IgM MC in patients without lymphoma, above all IgM-associated neuropathy (30-50%). Significant symptoms or risk of organ damage, require treatment directed to the malignant clone. For minimally symptomatic patients, supportive care may be sufficient. Assessment of health-related QuoL (HRQuoL) is becoming a critical component of disease outcome evaluation, predicting in some cases patient survival. The concept of HRQuoL in fact, encompasses several aspects of a patients' well-being, ranging from physical health to functional, psychological, and social features. In the last decade, specific questionnaires were introduced for patients with different hematological malignancies to supplement the EORTC QLQ-C30. Considering WM and IgM-MGUS/IgM-RD clinical heterogeneity, their chronicity and advanced median age at presentation, HRQuoL assumes even greater importance in this setting. Despite this, there are no studies addressing the impact of Eastern Cooperative Oncology Group (ECOG) performance status and comorbidities on patients' outcome. Furthermore, HRQuoL has never been evaluated in this category. In this study, we analyzed the impact of diagnosis and patients' characteristics on QuoL. From October 2017 to January 2019, HRQuoL was assessed in 143 subjects with WM or IgM-MGUS/IgM-RD in our Institute through the administration of EORTC QLQ-C30, HADS, FACTGOG neurotoxicity, and EQ-5D-5 L questionnaires. Patients with IgM MC and BM infiltration by a lymphoproliferative disorder apart from LPL were excluded. Demographic anamnestic and diseaserelated data were collected. The same questionnaires continue to be administered every 6 months for 3 years to capture changes in HRQuoL over time. All participants signed an informed consent according to ethical guidelines and principles of the international Declaration of Helsinki. Here, we present results from the baseline evaluation. Among the 143 patients, 47 were treated WM (t-WM): 30 previously treated; 17 in treatment with BCR inhibitors. Fortythree patients had untreated disease (ut-WM). Despite none of them having received WM-specific therapy, in nine cases, supportive treatment with low-dose pregabalin was effectively administered for mild neuropathy. Among the 53 patients with IgM-MGUS/IgM-RD, six were defined IgM-RD due to peripheral neuropathy. Patients' characteristics are reported in Table 1. No differences were noted among the three groups. Twelve patients showed ECOG ≥3:6 t-WM; 5 ut-WM, and 1 IgM-MGUS/IgM-RD. Cumulative Illness Rating Scale (CIRS) score > 6 was recorded in 18; 21 and 17 tWM, utWM and IgM-MGUS/IgM-RD, respectively. Vascular and genitourinary were the main systems involved. Genitourinary, vascular, musculoskeletal, and respiratory were the systems most commonly presenting CIRS score of 3-4. No statistical differences were found among the three groups when analyzing EORTC QLQ-C30 global health status, functional scales (physical, role, emotional, cognitive, and social functioning) and symptoms scale, HADS anxiety and depression scores or FACT-GOG neurotoxicity score. Notably, EQ-5D VAS score resulted significantly worse in tWM compared to both utWM and IgM-MGUS/IgM-RD but did not differ when comparing utWM vs IgM-MGUS/IgM-RD. To evaluate the impact on HRQuoL, all patients, independently of diagnosis, were stratified according to clinical and disease characteristics. Patient-related conditions such as age, higher ECOG performance status and higher CIRS score negatively influenced HRQuoL. Importantly, even in cases of ut-WM and IgM-RD receiving only symptomatic pregabalin treatment with apparent satisfactory symptoms containment, IgM-related neuropathy was detrimental on QuoL. Time from diagnosis did not affect patients' well-being. Results are summarized in Table 2. Received: 11 November 2019 Revised: 25 November 2019 Accepted: 26 November 2019