Characteristics and outcomes of secondary hematological malignancies following autologous stem cell transplantation for multiple myeloma

Autologous stem cell transplantation (auto-SCT) remains an important pillar in multiple myeloma (MM) therapy; however, there is an increased risk of developing second primary malignancy including second hematological malignancy (SHM). We performed a retrospective study of patients with MM who underwent an auto-SCT at our institution between 1990 and 2022 and subsequently developed SHM. Among 3401 patients with MM who underwent auto-SCT, 110 (3.2%) developed SHM [therapy related myeloid neoplasm (t-MN) = 98; acute B cell lymphoblastic leukemia (t-B-ALL) = 11 and mixed phenotype acute leukemia=1). The cumulative incidence of SHM has increased between the pre-novel (auto-SCT, 1990-2006) and novel agent eras (2007- 2022) (1.1% vs 2.0% at 60 months; P = 0.03). Somatic mutations in TP 53 gene were seen in 40% of patients with t-MN. Among t-B-ALL patients, high incidence of hypodiploidy (n = 4) and IKZF1 (n = 3) deletion was observed. In multivariate analysis, receiving an alkylator based induction, radiation therapy, achieving a complete response after auto-SCT, use of cyclophosphamide for stem cell mobilization and lenalidomide maintenance were independent predictors of developing SHM. Patients with MM who developed a SHM had an inferior overall survival (OS). Given the median OS for MM continues to improve, monitoring for SHM and risk mitigation strategies is crucial.