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The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P < .001 and HR 5.01, P < .001, respectively) and OS (HR 3.85, P < .001 and HR 8.13, P < .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Primary myelofibrosis (PMF) is associated with morbidity and mortality. Ruxolitinib gained US FDA approval for treatment of intermediate/high-risk PMF in November 2011. We evaluated differences in survival and second primary malignancy (SPM) incidence among US PMF patients in the years before and after ruxolitinib approval., Methods: We conducted a retrospective study utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 database for PMF patients. We divided patients into five-year cohorts pre- (2007-2011) and post-ruxolitinib (2012-2016) approval and compared relative survival rates (RSRs) to the standard population and standardized incidence rates (SIRs) of SPMs between cohorts., Results: We included 2020 patients diagnosed with PMF from 2007-2016 in this study. There was no difference in the four-year RSRs between cohorts (54 % vs. 57 %, p = 0.776). More patients developed SPMs in the post-ruxolitinib cohort (8% vs. 6%, p = 0.041). The majority of SPMs were hematologic with higher incidence of AML transformation in the post-ruxolitinib cohort (SIR 125.29 vs. 70.55)., Conclusions: PMF prognosis remains poor in the years following ruxolitinib's approval. SPM incidence including AML transformation is higher in the years after approval. Further studies are needed to determine the true impact of ruxolitnib on population outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)