Ondansetron and Hypothermia Induced Cardiac Arrest in a 97-Year-Old Woman: A Case Report

Background: Ondansetron and hypothermia are both known to induce bradycardia or QT interval prolongation, thus placing affected patients at risk of cardiac arrest. Case Report: Herein, we report the case of a 97-year-old woman who initially presented with confusion and hypothermia, and experienced severe bradycardia and asystolic cardiac arrest after a 4 mg intravenous ondansetron bolus injection. Conclusion: Ondansetron is associated with bradycardia and QTc prolongation, both of which might be further exacerbated by hypothermia. Clinicians should be aware that administering ondansetron in patients with hypothermia might further increase the risk of adverse cardiac events and eventual cardiac arrest

Impact of Second Primary Malignancy Post–Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis

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 \u3c .001 and HR 5.01, P \u3c .001, respectively) and OS (HR 3.85, P \u3c .001 and HR 8.13, P \u3c .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

Impact of Induction Therapy with VRD versus VCD on Outcomes in Patients with Multiple Myeloma in Partial Response or Better Undergoing Upfront Autologous Stem Cell Transplantation

Bortezomib-based triplet regimens—specifically bortezomib, lenalidomide, and dexamethasone (VRD) and bortezomib, cyclophosphamide, and dexamethasone (VCD)—are the 2 most common induction regimens used in transplantation-eligible patients with newly diagnosed multiple myeloma (NDMM), with conflicting data on comparative efficacy and outcomes in this population. We compared long-term outcomes of patients with NDMM receiving VRD induction and those receiving VCD induction prior to autologous stem cell transplantation (ASCT). Patients registered with the Center for International Blood and Marrow Transplant Registry were included if they had undergone ASCT for MM within 6 months of diagnosis between January 2013 and December 2018, received VRD or VCD induction, and achieved a pretransplantation partial or better response. Of 1135 patients, 914 received VRD and 221 received VCD. The patients receiving VCD were more likely to have renal impairment and International Staging System (ISS) stage III disease and less likely to receive full-dose melphalan (200 mg/m2) conditioning (69% versus 80%; P < .001). Very good partial response rates pretransplantation, post-transplantation, and at best response were not significantly different in the 2 groups. Maintenance use was more common after VRD induction (88% versus 76%; P < .001), with lenalidomide the most common agent (80% versus 63%). Patients in the VRD group had a higher rate of renal recovery (74% versus 43%; P < .001), possibly due to a rapid reduction of light chains in the VRD group or improvement in renal function with VCD, which allowed a switch over to VRD, as patients who switched were classified in the VRD group. Patients receiving VRD had better survival on univariate analysis, with a median progression-free survival (PFS) from transplantation of 44.6 months versus 34.1 months (P = .004) and median 5-year overall survival (OS) of 79% versus 60% (P < .001). Multivariate analysis showed no significant survival difference, with a hazard ratio for VCD versus VRD induction of 1.22 (95% CI, 0.96 to 1.55; P = .10) for PFS and 1.33 (95% CI, 0.93 to 1.92, P = .12) for OS. Maintenance use was independently associated with superior PFS and OS, along with ISS stage, cytogenetics, and pretransplantation response (PFS only). In patients with MM undergoing upfront ASCT after VRD or VCD induction, no independent survival difference was seen based on the induction therapy received after adjusting for other prognostic factors. The use of maintenance treatment was uniformly associated with superior outcomes. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc

Age no bar : a CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma

BACKGROUND: Upfront autologous hematopoietic cell transplantation (AHCT) remains an important therapy in managing multiple myeloma (MM), a disease of older adults. METHODS: We investigated the outcomes of AHCT in MM in patients aged 70 years and older (≥70). The CIBMTR database registered 15,999 U.S. MM patients within 12 months of diagnosis during 2013–2017; 2,092 patients were ≥70. Non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS) were modeled using Cox proportional hazards with age at transplant as the main effect. Because of the large sample size, a p-value of <0.01 was considered significant a priori. RESULTS: An increase in AHCT was noted in 2017 (28%) compared to 2013 (15%) in ≥70. While 82% patients received melphalan (Mel) 200 mg/m(2) overall, 58% of the patients ≥70 received Mel 140 mg/m(2). On multivariate analysis, patients ≥70 had no difference in NRM (hazard ratio (HR) 1.3, 99% confidence interval (CI) 1, 1.7, p 0.06), REL (HR 1.03, 99% CI 0.9–1.1, p 0.6), PFS (HR 1.06, 99% CI 1–1.2, p 0.2), and OS (HR 1.2, 99% CI 1–1.4, p 0.02) compared to the reference group (60–69 years). In patients ≥70, Mel 140 mg/m(2) was associated with worse outcomes compared to Mel 200 mg/m(2) including day-100 NRM 1 (1–2)% vs 0 (0–1)%, p 0.003, 2-year PFS 64 (60–67)% vs 69 (66–73)%, p 0.003, and 2-year OS 85 (82–87)% vs 89 (86–91)%, p 0.01, respectively, likely representing frailty. CONCLUSION: We conclude that AHCT remains an effective consolidation therapy across all MM age groups

Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with 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 employing 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 MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). 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 (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% versus 30% and 53% versus 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in MM patients 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