Kapoor, Prashant

Background:Previous literature has established “long‐term survivors” as patients who survive greater than 10 years from diagnosis of active multiple myeloma (MM). With the rapid discovery and evolving use of novel therapeutic agents, a greater proportion of patients are reaching this milestone. Although these patients share in their extended survival, they also constitute a heterogeneous group in terms of treatments and outcomes.Aims:The aim of this study is to examine a large cohort of long‐term survivors with protracted follow‐up as an attempt to identify a subset of patients within ten‐year survivors who have longstanding disease remission, and examine the predictors of their especially exceptional prognosis.Methods:All patients with active MM evaluated at Mayo Clinic, Rochester between January 1, 1999 and July 1, 2008 were included in the study. Patients with MGUS, smoldering MM, and solitary plasmacytoma were excluded. The overall survival (OS) was calculated from time of symptomatic disease requiring treatment. Patients with greater than 10 year survival from diagnosis were then divided into three cohorts based upon treatment and remission status: Cohort 1 included patients off therapy ≥ 5 years and in sustained remission, Cohort 2 included patients on maintenance therapy ≥ 5 years and in sustained remission, and Cohort 3 included patients who had relapsed within the past 5 years. Differences between the groups were compared using Wilcoxon, Chi‐square, and Fisher's exact test as applicable. “Early” stem cell transplant was defined as patients who received a stem cell transplant within one year of diagnosis.Results:During the time frame of the study, 2,125 patients were identified who fulfilled the diagnostic criteria for active MM. Three‐hundred ninety nine (19%) had survived at least 10 years from diagnosis. Among these patients, based on the available data regarding remission and ongoing treatment status, 332 patients were categorized into three cohorts, seen in Table 1. Sixty patients (18% of long‐term survivors) comprised Cohort 1, 48 patients (14% of long‐term survivors) comprised Cohort 2, and 224 patients (68% of long‐term survivors) comprised Cohort 3. Sex difference was statistically significant between the groups, with more females constituting Cohorts 1 and 2 (p = 0.03). Within Cohort 1, 77% of patients underwent an autologous stem cell transplant (ASCT). The median progression free survival following ASCT in this cohort was not reached (95% CI 15–NR, p < 0.001). In addition, patients in Cohort 1 and Cohort 2 were more likely to undergo an early ASCT as compared to patients in Cohort 3 (p = 0.002). There were no significant differences in high or intermediate risk FISH/cytogenetics at diagnosis, ISS at diagnosis, or induction therapies used at diagnosis among the three groups.Summary/Conclusion:Our study identified a small subset (3% of all patients diagnosed with active MM) of long‐term survivors who are off of therapy and remain in sustained longstanding remission. Female sex, progression free survival following ASCT, and receiving an early ASCT were factors that portended a positive prognosis amongst long term survivors.image

BACKGROUND Waldenström macroglobulinemia (WM) is preceded by asymptomatic WM (AWM), for which the risk of progression to overt disease is not well defined. METHODS We studied 439 patients with AWM, who were diagnosed and observed at Dana-Farber Cancer Institute between 1992 and 2014. RESULTS During the 23-year study period, with a median follow-up of 7.8 years, 317 patients progressed to symptomatic WM (72%). Immunoglobulin M 4,500 mg/dL or greater, bone marrow lymphoplasmacytic infiltration 70% or greater, β2-microglobulin 4.0 mg/dL or greater, and albumin 3.5 g/dL or less were all identified as independent predictors of disease progression. To assess progression risk in patients with AWM, we trained and cross-validated a proportional hazards model using bone marrow infiltration, immunoglobulin M, albumin, and beta-2 microglobulin values as continuous measures. The model divided the cohort into three distinct risk groups: a high-risk group with a median time to progression (TTP) of 1.8 years, an intermediate-risk group with a median TTP of 4.8 years, and a low-risk group with a median TTP of 9.3 years. We validated this model in two external cohorts, demonstrating robustness and generalizability. For clinical applicability, we made the model available as a Web page application ( www.awmrisk.com ). By combining two cohorts, we were powered to identify wild type MYD88 as an independent predictor of progression (hazard ratio, 2.7). CONCLUSION This classification system is positioned to inform patient monitoring and care and, for the first time to our knowledge, to identify patients with high-risk AWM who may need closer follow-up or benefit from early intervention.