Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies

Abstract

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous

Survival trends in young patients with Waldenström macroglobulinemia: Over five decades of experience

“…These discrepencies are potentially related to referral bias to a tertiary center, to which the fitter, and oftentimes, younger patients are able to travel. The 10‐year OS (74%) observed in younger patients from our study was lower than that of an Italian study (97%) of young (≤55 years) WM patients, 24 likely due to the evaluation of a more recent cohort (2000–2019) in the latter study which also included patients receiving BTKi‐based regimens. As expected, in our study, younger WM patients had significantly longer OS and DSS compared to the older patient group, over five decades, likely in the context of overall better functional reserve and fewer comorbidities 9 .…”

“…17 These discrepencies are potentially related to referral bias to a tertiary center, to which the fitter, and oftentimes, younger patients are able to travel. The 10-year OS (74%) observed in younger patients from our study was lower than that of an Italian study (97%) of young (≤55 years) WM patients, 24 17 Although not addressed in our study, changes in WM management over the time period may have had an impact on other aspects of patient care, including quality of life and improved tolerability of therapy, that may not directly have a noticeable impact on survival.…”

Real‐world treatment patterns and outcomes in a national study of veterans with Waldenström macroglobulinemia, 2006–2019

“…We are the first to report real-world response rates to WM treatment in a cohort including both older and younger patients. 3 We observed an ORR of 72.3%, lower than an ORR aggregated from clinical trials of rituximab-based therapy (ORR: 84%, 95% CI: 81-87%). 4 The difference is unsurprising, since more than 30% of our cohort received 1 L single-agent rituximab, which achieves ORR in approximately 47% of patients.…”

“…In CLL, mutations in NOTCH1 have been shown to be associated with advanced stage at diagnosis, short TTFT, worse overall survival, and increased risk of Richter's transformation 2. Several proteins interact with and negatively regulate NOTCH1 activity, including MED12, FBXW7, and SPEN [3][4][5]. Mutations impacting the function of these proteins and limiting their ability to regulate the activity of NOTCH1 may impact CLL biology and influence patient outcomes via NOTCH1 activation.In order to better understand the clinical relevance of MED12, FBXW7, and SPEN mutations in CLL patients at diagnosis, we conducted a retrospective study to establish clinical characteristics and initial clinical behavior of patients with mutations compared to those who are wild-type for MED12, FBXW7, and SPEN.…”

SOHO State of the Art Updates and Next Questions: Targeted therapies and emerging novel treatment approaches for Waldenström Macroglobulinemia

“…2,3 Clinical manifestations frequently include anemia, constitutional symptoms, lymphadenopathy, splenomegaly as well as IgM-related syndromes such as hyperviscosity, peripheral neuropathy, cryoglobulinemia, cold agglutinin disease, and amyloidosis. [4][5][6]…”