RESUMO
Background: The Sarah Cannon Transplant and Cellular Therapy Network (SCTCTN), which offers community access to transplant and cell therapy, implemented a coordinated approach to deliver CAR-T therapy through 5 programs. We conducted a retrospective review of clinical outcomes after FDA-approved anti-CD19+ CAR-T in B-cell NHL. Method(s): All patients referred for evaluation within SCTCTN were tracked in our prospective registry (Stafa-CT). We identified 110 patients who received FDA-approved anti-CD19+ CAR-T for NHL within the network between 12/10/2018 and 3/7/2022. All patients received care through standardized eligibility criteria, process, care pathways, toxicity management protocols, and a single quality plan. Result(s): The median age at referral was 60 years (range 23-82), 63% were male, the referral indication was diffuse large B-cell lymphoma (70%), mantle cell lymphoma (7%), follicular lymphoma (15%), or other B-NHL (8%). 35% had received a prior autologous transplant. The median time from referral to infusion was 143 days (range 89- 224), and from collection to infusion was 32 days. The infusion year was 2018 (1), 2019 (20), 2020 (31), 2021 (48), 2022 (10). The CAR-T cell products were Axi-cel (70), Tisa-cel (27), Brexu-cel (9), and Liso-cel (4). 16 patients (15%) were infused as outpatient, of which 10 patients were subsequently hospitalized at a median of 8 days (range 1-26) after infusion. Of the 94 patients (85%) infused as inpatient, the median length of stay was 15 days (range 6 to 85). Cytokine release syndrome (CRS) was observed in 78% with a median maximum grade 1. Maximum grade CRS was none, grade 1, grade 2, grade 3, grade 4, grade 5 in 22%, 36%, 32%, 7%, 2 % and <1%, respectively. The median times to onset and resolution of symptoms were day 3 and 8, respectively. Tocilizumab was administered to 39% for a median of 2 doses. Neurotoxicity was observed in 55% with a median maximum grade 1. Maximum grade neurotoxicity was none, grade 1, grade 2, grade 3, grade 4, grade 5 in 45%, 19%, 13%, 18%, 4 % and 0%, respectively. The median times to onset and resolution of symptoms were day 7 and 13, respectively. Neutropenia (<0.5/ muL) and thrombocytopenia (<20K/muL) at day 30 were reported in 11% and 12%, respectively. 18% required ICU stay. 37 deaths (34%) were reported from disease progression (23), infections (7, including 5 from COVID), CRS (2) and other causes (5).(Figure Presented) Conclusion(s): Administration of anti-CD19+ CAR-T is feasible in specialized community hospitals with outcomes similar to registrational clinical trials. Outpatient administration is feasible in selected patients, but subsequent hospitalization needs to be anticipated. CRS, neurotoxicity, cytopenias and infection remain challenges, while disease progression was the commonest cause of deathCopyright © 2023 American Society for Transplantation and Cellular Therapy
RESUMO
Background: Timely administration of antibiotics in patients with neutropenic fever (NF) is essential for reducing morbidity and mortality among oncology patients. Due to their immunocompromised state, neutropenic patients are at particularly high risk of developing severe complications from infection. The optimal time to antibiotics (TTA) for patients with NF is unclear, but IDSA/ASCO guidelines recommend a median TTA within one hour of documented fever. This study focused on identifying barriers at a single academic institution to timely antibiotic administration for patients admitted to the inpatient Bone Marrow Transplant (BMT) unit, and implemented new processes to reduce median TTA to less than 60 minutes. Method(s): Patients who developed NF during their hospital admission were included in the study. Individuals who were transferred from another facility or presented to the Emergency Department with NF were excluded. Chart reviews were performed to identify root causes for delays in antibiotics (abx). Data was collected for the following time points: time from fever to notification of provider, time from notification to abx order, time from order to release, and time from release to administration. The research team also met with key stakeholders from nursing, pharmacy, advance practice providers, and physicians to better understand the process. Result(s): Based on the root cause analysis, 4 interventions were implemented: cefepime was stocked in the pyxis (Int 1 - August 2018), NF guidelines were updated (Int 2 - October 2019), Educational videos were created for just in time learning for house staff rotating on the oncology services and an education campaign for the nursing staff (Int 3 - June 2020), a nurse driven protocol to release and administer abx was piloted on the BMT (Int 4 - December 2021). Baseline TTA was 128 minutes. After Int 1, median TTA decreased to 77.2 minutes. Int 2 and Int 3 did not improve median TTA. In October 2020, median TTA had increased to 98 minutes. After Int-4, on the BMT unit, median TTA decreased to 40 minutes. Conclusion(s): Through iterative changes and process improvement methodology, we were able to improve our median TTA from 128 minutes to 40 minutes. The most impactful changes simplified the process to administer abx. Educational initiatives were less impactful, which is consistent with human factor re-engineering science and change management strategies. This improvement initiative spanned over an extended time period largely because of interruptions due to the COVID pandemic. As a result, the project demonstrated that the goal to implementing and sustaining change requires workflow redesign, culture shifts, and engagement by all key stakeholders.