Management Patterns and Outcomes for Multiple Myeloma Patients with High-Risk Cytogenetics at an Urban Safety Net Hospital

Abstract

Background: Over the past decade, there have been tremendous advancements and drug approvals for multiple myeloma (MM). This is especially true with the advent of therapies such as chimeric antigen T-cell receptor therapy (CART). As a result, patients with MM are living longer; with many patients living a decade or longer. However, there is still a small subset of patients with high-risk disease that unfortunately continue to do poorly. High-risk disease based on cytogenetics is defined by disease specific biologic features such as t(4;14), del17p, t(14;16), t(14;20), and gain of 1q. Patients with such features tend not to respond as well to induction therapies and autologous stem cell transplantation as those with standard risk cytogenetics. Here we report a retrospective cohort of patients with high-risk cytogenetics to evaluate patient characteristics, management patterns, and outcomes in an urban safety net hospital. Methods: We performed a retrospective chart review of all patients aged 18 years or older who presented to Harbor-UCLA Medical Center between 2008-2022 with the diagnosis of MM. Patients were included if they were 18 years or older, had MM based on IMWG criteria, and had high risk cytogenetics defined as having one or more of the following abnormalities: t(4;14), del17p, t(14;16), t(14;20), and gain of 1q. Data collected included demographics, induction regimens, transplant status, response, consolidation therapy, progression free survival (PFS) on first line therapy, and overall survival (OS). Results: We identified 28 MM patients with high-risk cytogenetics. The median age at diagnosis was 65, and the cohort was 79% Hispanic, 10% Asian, 7% African American, and 4% Caucasian. 54% of patients were female and 46% were male. Cytogenetic abnormalities were prevalent in the following order: deletion 17p (50%), gain of 1q (29%), t(4;14) (18%), t(14;16) (3%). The most used induction regimen was cyclophosphamide, bortezomib, and dexamethasone (CyBorD) (71%) followed by revlimid, velcade, and dexamethasone (RVD) (25%). Only 32% of patients received autologous stem cell transplantation. The most common drug used in the maintenance setting was velcade (50%). The median PFS for first line treatment in patients with high-risk cytogenetics was 14 months (18.1 months average). The median OS was 29 months (average 37.6 months). Conclusion: In this high-risk patient population, with few resources available, we found that the majority of patients were treated with CyBorD, primarily due to kidney disease or inability to access revlimid upfront. In addition, the majority of patients did not receive autologous stem cell transplantation, which is considered standard of care for upfront management of MM, especially in patients with high-risk cytogenetics. Our centers median PFS for first line treatment was 14 months, which was significantly lower compared to other published data with reported PFS of around 37 months. In addition, our median OS of 29 months was also lower compared to reported OS at other centers of around 60 months. This is most likely due to the low utilization of RVD upfront and transplantation, among other comorbidities that are unique to our population. Further research is needed to characterize real world outcomes and elucidate mechanisms of disparity.