Early Use Of Steroids Research Articles

Real World Experience with a Zuma -1 Cohort 4 Adopted Approach to CRS and Icans in CAR-T Recipients

Introduction: Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor T-cell (CAR-T) therapy approved for treatment of relapsed/refractory (R/R) large B cell lymphoma (LBCL). The registrational phase I/II ZUMA-1 study Cohorts 1 and 4 addressed toxicity management in terms of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) whereby tocilizumab and corticosteroids were deployed earlier in Cohort 4.(1,2) Although Cohort 4 consisted of only 41 patients, it demonstrated that earlier intervention resulted in significantly fewer cases of grade ≥3 CRS (2%) and ICANS (17%) and a lower cumulative dose of steroids. Furthermore, efficacy as determined by overall response rate (ORR) and complete response (CR) did not appear to be negatively impacted by earlier use of tocilizumab and corticosteroids. However, given the small number of patients in Cohort 4, concern has remained that earlier intervention may have a deleterious impact on CAR-T cell expansion, persistence, and efficacy. During the COVID-19 pandemic, with overwhelmed Intensive Care Units (ICUs) across the country, we adopted a Cohort 4 guided approach to CAR-T toxicity management with the hope of decreasing the need for ICU level of care following CAR-T infusion. Herein, we present our single-institution, real-world experience since implementing an early intervention strategy with Cohort 4 and compare it with our previous Cohort 1 axi-cel recipients in terms of toxicity (CRS, ICANS, ICU utilization) and efficacy. Methods: 119 patients receiving axi-cel CAR-T therapy for R/R LBCL are included in this single-institution, retrospective study with 70 in Cohort 1 and 49 in Cohort 4. The transition from a Cohort 1 to Cohort 4 approach occurred in March 2021. Thus, for Cohort 1 the data cut-off was February 2021 and for Cohort 4 it was after April 2021. The COVID pandemic and the lack of the ICU capacity was the initial chief rationale for transitioning to Cohort 4. This study was conducted following IRB approval and in accordance with the Declaration of Helsinki. R version 1.3.1099 (R-studio) was used for all statistical modeling. All statistical tests were 2-sided and conducted at the 0.05 level of significance. Results: The median age was 62 (22-88) years-old, 35% female gender, 76% advanced stage III-IV disease, 22% with bulky ≥10cm disease, 71% with diagnosis of Diffuse LBCL, and 26% with more than three lines of previous therapy. The median follow-up time at analysis was 1.5 years. Laboratory parameters and comorbidities did not significantly differ between groups except for a higher incidence of renal insufficiency in the Cohort 4 group (28.6% vs 4.3%, p<0.001) (see Table 1). The median maximum grade CRS was significantly lower for Cohort 4 (2 vs 1, p<0.001) although the median grade of ICANS was not different. The utilization of tocilizumab and siltuximab was similar in both groups. The duration of steroid use was comparable in both; however, the total steroid use (dexamethasone equivalent) was notably lower in Cohort 4 (110 mg vs 190 mg, p=0.026). ICU admission following CAR-T infusion was much lower in Cohort 4 (16.3% vs 60%, p<0.001). Most patients (>80%) were discharged home after CAR-T therapy and did not need placement in a rehabilitation center or long-term facility. The ORR and ongoing responses were similar in both groups with nearly 90% achieving a response and 60% with an ongoing response. The cumulative incidence of relapse, PFS, and OS were not significantly different between the groups (see Figure 1). Conclusion: The use of an early toxicity intervention strategy based upon ZUMA-1 Cohort 4 in the real world results in significantly lower high-grade CRS, decreased cumulative steroid dose, and an 73% reduction in ICU utilization without significantly impacting efficacy in terms of incidence of relapse, PFS, or OS. Our real-world experience with the adoption of a Cohort 4 strategy suggests that patient morbidity may be greatly attenuated without compromising CAR-T therapy response. However, the need for longer follow-up to evaluate the impact early use of steroids has on CAR-T persistence and PFS at >5 years remains.

Survival Among Veterans Receiving Steroids for Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy

Systemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy. To characterize how systemic steroids and steroid timing for irAEs are associated with survival in patients receiving ICI therapy. This multicenter retrospective cohort study encompassed veterans receiving ICI for cancer between January 1, 2010, and December 31, 2021. Data analysis was conducted September 8, 2023. Identifiable primary diagnosis of cancer. Patients were categorized into 3 cohorts: those receiving no steroids, systemic steroids for irAEs, and steroids for non-irAE-associated reasons. All eligible patients received 1 or more doses of an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab). Eligible patients in the steroid group received at least 1 dose (intravenous, intramuscular, or oral) of dexamethasone, hydrocortisone, methylprednisolone, prednisone, or prednisolone. Steroid use at baseline for palliation or infusion prophylaxis or delivered as a single dose was deemed to be non-irAE associated. All other patterns of steroid use were assumed to be for irAEs. The primary outcome was overall survival, with a 5-year follow-up after ICI initiation. Kaplan-Meier survival analyses were performed with pairwise log-rank tests to determine significance. Risk was modeled with Cox proportional hazard regression. The cohort consisted of 20 163 veterans receiving ICI therapy including 12 221 patients (mean [SD] age, 69.5 [8.0] years; 11 830 male patients [96.8%]; 9394 White patients [76.9%]) who received systemic steroids during ICI treatment and 7942 patients (mean [SD] age, 70.3 [8.5] years; 7747 male patients [97.5%]; 6085 White patients [76.6%]) who did not. Patients with an irAE diagnosis had significantly improved overall survival (OS) compared with those without (median [IQR] OS, 17.4 [6.6 to 48.5] months vs 10.5 [3.5 to 36.8] months; adjusted hazard ratio, 0.84; 95% CI, 0.81-0.84; P < .001). For patients with irAEs, systemic steroids for irAEs were associated with significantly improved survival compared with those who received steroids for non-irAE-related reasons or no steroid treatment (median [IQR] OS, 21.3 [9.3 to 58.2] months vs 13.6 [5.5 to 33.7] months vs 15.8 [4.9 to not reached] months; P <.001). However, among those who received steroids for irAEs, early steroid use (<2 months after ICI initiation) was associated with reduced relative survival benefit vs later steroid use, regardless of ICI continuation or cessation following steroid initiation (median [IQR] OS after ICI cessation 4.4 [1.9 to 19.5] months vs 16.0 [8.0 to 42.2] months; median [IQR] OS after ICI continuation, 16.0 [7.1 to not reached] months vs 29.2 [16.5 to 53.5] months; P <.001). This study suggests that steroids for irAE management may not abrogate irAE-associated survival benefits. However, early steroid administration within 2 months of ICI initiation is associated with shorter survival despite continuation of ICI therapy.

Optimizing vestibular neuritis management with modular strategies.

This study proposes a "modular management" approach for vestibular neuritis (VN) to reduce chronicization and improve patient prognosis. The approach involves multi-factor grading and hierarchical intervention and was found to be more effective than traditional treatment strategies. This retrospective analysis compared two groups of VN patients from two medical institutions. The intervention group of 52 patients received "modular management," while the control group of 51 patients did not receive this kind of management. Analyzed the early treatment strategies, 6-month prognosis, and other indicators of the two groups of patients, compared and analyzed their overall prognosis, and identified the risk factors affecting the chronicization. The modular management group had lower dizziness severity, better balance, lower anxiety, and higher video head impulse testing (v-HIT) gain after 6 months of onset. Analysis of factors related to persistent postural-perceptual dizziness (PPPD) in patients with VN showed positive correlations between the time from onset to diagnosis and PPPD, and Vertigo Symptom Scale (VSS), Dizziness Handicap Inventory (DHI), anxiety, and depression. Normalized vestibular rehabilitation was negatively correlated with PPPD, while gender, age, and early steroid use had no significant correlation. The multi-factor logistic regression model correctly classified 93.20% of the study subjects with a sensitivity of 87.50% and specificity of 94.90%. The proposed "modular management" scheme for VN is a comprehensive and dynamic approach that includes health education, assessment, rehabilitation, therapy, evaluation, and prevention. It can significantly improve patient prognosis and reduce chronicization by shifting from simple acute treatment to continuous management.

P18 Epidermolysis bullosa acquisita in children: report of three cases

Abstract Epidermolysis bullosa acquisita (EBA) is an acquired, subepidermal blistering skin disease characterized by autoantibodies against type VII collagen, which links the epidermis to the dermis at the dermo-epidermal junction. Clinically, patients have skin fragility and blisters over trauma-prone sites, scarring, milia and onychodystrophy. The diagnosis can be challenging as it shares clinical and histopathological features with other immunobullous diseases. Although exceptionally rare in children, we report three paediatric patients with EBA and variable disease severity. The main clinical features were blisters (n = 3), milia (n = 3), scarring (n = 2), oral erosions (n = 2) and onychodystrophy (n = 1). Histological findings were nonspecific, showing a subepidermal blister with various inflammatory infiltrates. On direct immunofluorescence a bright deposit of IgG was seen, and the antibodies adhered to the dermal side of the salt-split in two cases. ELISA analysis confirmed circulating autoantibodies against type VII collagen in one patient. All received a course of oral corticosteroids alongside steroid-sparing agents such as dapsone, azathioprine and rituximab depending on clinical response and shared favourable prognosis. Early use of topical steroids can help but high-dose oral corticosteroids are often required as well as steroid-sparing agents such as dapsone, methotrexate, azathioprine, ciclosporin, mycophenolate mofetil, cyclophosphamide and rituximab. In our experience, although the treatment approaches have been different, all the patients had favourable outcomes.

Immuntherapie in der Hepatogastroenterologie: Wirkung und Nebenwirkung

Immune-checkpoint-inhibitors (ICI) are used for adjuvant therapy of squamous cell carcinoma and adenocarcinoma of the esophagogastric junction after prior radiotherapy. The combination of ICI with chemotherapy (CTx) is approved for first-line therapy in a palliative setting (Nivolumab and Ipilimumab) and as second-line option (Nivolumab). Squamous cell carcinoma probably has a higher response rate to ICI and Nivolumab and Ipilimumab are approved as a single therapy for this entity. ICI combined with CTx is approved for metastatic gastric cancer. MSI-H tumors respond well to ICI and can be treated with Pembrolizumab in second line. ICI are only approved for MSI-H/dMMR CRC. Pembrolizumab is a first-line option and Nivolumab combined with Ipilimumab a second-line therapy. Atezolizumab with Bevacizumab is the new first-line therapy of advanced HCC, with additional ICI combinations with positive Phase III studies expected to be approved in the near future. Durvalumab and CTx achieved promising results in a recent Phase 3 study. Pembrolizumab is already EMA-approved as a second-line therapy of MSI-H/dMMR biliary cancer. ICI have not yet achieved a breakthrough in the therapy of pancreatic cancer. FDA-approval exists only for the small subgroup of MSI-H/dMMR tumors. The disinhibition of the immune response by ICI can cause irAE. IrAE most frequently affect the skin, gastrointestinal tract, liver, and endocrine organs. Starting with grade 2 irAE, ICI should be paused, differential diagnosis excluded and if necessary steroid therapy has to be started. Early high-dose use of steroids negatively affects patient outcome. New therapy strategies for irAE are currently tested, such as extracorporeal photopheresis, but larger prospective trials are lacking.

Hospital-acquired bloodstream infections in patients deceased with COVID-19 in Italy (2020-2021).

In hospitalized patients with COVID-19, bloodstream infections (BSI) are associated with high mortality and high antibiotic resistance rates. The aim of this study was to describe BSI etiology, antimicrobial resistance profile and risk factors in a sample of patients deceased with COVID-19 from the Italian National COVID-19 surveillance. Hospital charts of patients who developed BSI during hospitalization were reviewed to describe the causative microorganisms and their antimicrobial susceptibility profiles. Risk factors were analyzed in univariate and multivariate analyses. The study included 73 patients (71.2% male, median age 70): 40 of them (54.8%) received antibiotics and 30 (41.1%) systemic steroids within 48 h after admission; 53 (72.6%) were admitted to intensive care unit. Early steroid use was associated with a significantly shorter interval between admission and BSI occurrence. Among 107 isolated microorganisms, the most frequent were Enterococcus spp., Candida spp., Acinetobacter baumannii, and Klebsiella pneumoniae. Median time from admission to BSI was shorter for Staphylococcus aureus compared to all other bacteria (8 vs. 24 days, p = 0.003), and longer for Enterococcus spp., compared to all other bacteria (26 vs. 18 days, p = 0.009). Susceptibility tests showed a high rate of resistance, with 37.6% of the bacterial isolates resistant to key antibiotics. Resistance was associated with geographical area [adjusted odds ratio (AOR) for Central/South Italy compared to North Italy: 6.775, p = 0.002], and with early use of systemic steroids (AOR 6.971, p = 0.018). In patients deceased with COVID-19, a large proportion of BSI are caused by antibiotic-resistant bacteria. Early steroid use may facilitate this occurrence.

Clinicopathological Characteristics of Drug-Induced Acute Interstitial Nephritis and Role of Steroids in Management: A Single-Center Observational Study

Background: Acute interstitial nephritis (AIN) is a potentially reversible, but underdiagnosed cause of acute kidney injury. The role of steroids in the management of drug-induced AIN is debatable. There is scarcity of data on clinical characteristics of drug-induced AIN, management approach and effect of steroids on renal outcomes from the low-middle-income countries. Methods: We performed a retrospective study of patients with biopsy-proven AIN over a period of 12 years. The main outcomes were recovery of renal function (early (? 3 weeks) or late (&gt; 3 weeks)) and hemodialysis (HD) dependence at 12 weeks. Results: A total of 48 (4.9%) AIN cases were found among 978 renal biopsies. Mean age was 47.6 ± 12.1 years and 56.3% were males. The offending agent could be identified in half of the patients (non-steroidal anti-inflammatory drugs (NSAIDs) most commonly followed by antibiotics, diuretics and proton pump inhibitor (PPI)). Three quarters of patients presented with estimated glomerular filtration rate (eGFR) &lt; 15 mL/min/1.73 m 2 (n = 36), out of which 58.3% (n = 21) required HD. Thirty-nine (81.3%) patients ended up receiving steroids. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Early use of steroids (? 11 days) was significantly associated with earlier (? 21 days) onset of recovery (P = 0.003) as compared to late use of steroids (&gt; 11 days). Conclusion: Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery in drug-induced AIN in a low-middle-income country with frequent use of over-the-counter drugs. Late steroid use (? 3 weeks) was not associated with any further recovery at an additional risk of exposing patients to undue adverse effects. World J Nephrol Urol. 2022;11(1):24-30 doi: https://doi.org/10.14740/wjnu427

CAR-T Toxicity Management and Steroid Use in High-Grade B-Cell Lymphoma: Impact on Real-World Survival Outcomes in the UK

CAR-T Toxicity Management and Steroid Use in High-Grade B-Cell Lymphoma: Impact on Real-World Survival Outcomes in the UK

ADVANCED LUNG CANCER INFLAMMATORY INDEX AS A PROGNOSTIC MARKER FOR OXYGEN REQUIREMENT IN PATIENTS ADMITTED WITH SARS-COV-2 INFECTION

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: Severe acute respiratory syndrome coronavirus (SARS-COV-2) infection continues to spread at exponential rates globally with more than 145 million confirmed cases worldwide and over 3 million deaths. SARS-COV-2 presents with different clinical manifestations ranging from asymptomatic to severe infection, requiring various levels of O2 support, facing high rates of mortality. Systemic inflammatory response to the viral infection contributes to a variety of clinical manifestations and to the degree of severity of illness. Limited evidence exists on potential biomarkers to quantify severity and outcomes of SARS-COV-2 infection. Our objective is to see if Advanced lung cancer inflammation index (ALI) calculated at the time of admission to the hospital can be used as a prognostic marker for oxygen requirements and adverse clinical outcomes. METHODS: We conducted a retrospective chart review of all patients ages 18 and above admitted to Memorial Hermann Hospitals between March 1, 2020 to June 30, 2020 who tested positive for SARS-COV-2 by RT-PCR. The ALI was calculated using patients Body mass index (BMI), serum albumin and neutrophil/lymphocyte ratio (NLR) from the admission labs using the formula ALI= BMI (kg/m2) × albumin (g/dL)/NLR. Patient related information was obtained by reviewing medical records after obtaining Institutional review board approval. RESULTS: A total of 700 patients were identified out of which 417 patients had complete medical records for analysis. Patients were stratified into group A (high inflammation (ALI < 18) n = 205) and group B (low inflammation (ALI ≥ 18) n = 218). 67% of the patients were aged 45 or older. 52.5% of the patients had a BMI < 30. 22.3% of patients in group A, 22.3% and 16.7% patients in group B, 16.7% were of white race. ALI < 18 was associated with higher oxygen requirements (73% vs 52%, p ≥ 0.0001), higher mechanical ventilation requirements (16.59% vs 9.91%, p = 0.04) and higher mortality rates (14.15% vs 7.08%, p = 0.02). In multi-variate analysis, ALI < 18 was significantly associated with oxygen requirements, (OR 2.62 (1.64 - 4.17), p ≤ 0.0001). CONCLUSIONS: In patients diagnosed with SARS-CoV-2 infection, an ALI < 18, representing high systemic inflammation, calculated at the time of admission is associated with significantly increased oxygen requirements, severe disease and mortality. CLINICAL IMPLICATIONS: Advanced lung cancer inflammation index can be easily calculated from basic clinical parameters available in most clinical settings. It can be used as a tool in early identification of patients who are likely to have more severe respiratory disease and poorer outcomes in patients with SARS-COV-2 infections. Early use of steroids can be considered in this population of patients with an ALI <18. DISCLOSURES: No relevant relationships by Shailesh Advani, source=Web Response No relevant relationships by Syed Jafri, source=Web Response No relevant relationships by Pushan Jani, source=Web Response No relevant relationships by Arthi Sridhar, source=Web Response No relevant relationships by Wei Yang, source=Web Response

76. Effect of Early Administration of Systemic Corticosteroids on Outcomes in Patients with COVID-19 Pneumonia

BackgroundSystemic corticosteroids (steroids) have been empirically used in acute respiratory distress syndrome, an entity also present in coronavirus disease 19 (COVID-19). Early steroids administration could accelerate resolution of symptoms and reduce intensive care unit (ICU) stay in these patients, but practice varies widely as evidence is scant.MethodsWe reviewed the records of 498 adults admitted to Stony Brook University Hospital, NY, from 3/1 to 4/15, 2020 with COVID-19 requiring high-flow O2 (non-rebreather mask, Venturi mask with FiO2 >50%, or high-flow nasal cannula). We excluded those (N=29) who received mechanical ventilation (MV) or died within 24h of admission. We followed patients until death or discharge. We compared outcomes between patients who received early steroids (i.e. prior to MV) and those who did not. We used adjusted Cox models to evaluate the composite of death or need for MV. We also evaluated healthcare resources utilization.ResultsOf 469 patients, 175 (37.3%) received steroids while on high flow O2. Table 1 summarizes the baseline characteristics. Patients who received steroids were more likely to have asthma, had slightly longer duration of symptoms, lower O2 saturation, higher NT-proBNP and lower IL-6 levels at baseline. In total, 228 patients (48.6%) reached the composite endpoint (123 died and 105 received MV). By 7 days, 32.5% of patients who received steroids died or were intubated vs. 44.8% of those who did not (log-rank P=0.008), Figure 1. In models adjusted for race, age, sex, comorbidities, baseline O2 saturation and procalcitonin, steroids reduced risk for death or MV by 44% (hazard ratio [HR] 0.56; 95%CI 0.42–0.76; P< 0.001). The effect was time-dependent with initial HR 0.34 (95%CI 0.21–0.56; P< 0.001) and daily attenuation by 10.2% (95%CI 1.7%–19.4%; P=0.017). Mortality at 7 and 14 days did not differ between groups (8.1% vs. 8.3% and 19.1% vs. 21.0%, respectively, log-rank P=0.75). Among discharged patients, length of hospital stay was longer, but ICU stay was shorter with steroids, Table 2.Patient Characteristics According to Use of Early Steroids Healthcare Resources Utilization According to Use of Early Steroids Among Discharged Patients ConclusionEarly administration of steroids reduced primarily the need for MV in our high-risk COVID-19 patients, with shorter ICU utilization, at the expense of longer hospital stay. Further studies are needed to optimize the use of steroids in these patients.Disclosures All Authors: No reported disclosures

56. Could Maturation Effect Contribute to In-hospital Mortality Improvement During COVID-19 Pandemic?

BackgroundThe surge of COVID-19 cases overwhelms hospital systems necessitating rapid learning of the disease process and management. During the course of a novel pandemic, multiple interventions are rapidly implemented to improve patient outcomes. When evaluating efficacy of individual interventions, one should account for the simultaneous improvements in knowledge and experience of healthcare providers (HCP), known as the maturation effect. We hypothesized that multiple processes rapidly implemented, along with the maturation effect would result in improved survival of COVID-19 patients hospitalized over the course of the pandemic.MethodsThis retrospective study was done at Henry Ford Hospital (HFH), a 900-bed tertiary care facility in Detroit, Michigan. The first COVID-19 patient was hospitalized on March 10, 2020 followed by a rapid surge of cases. We evaluated the trends of in-hospital case fatality rate of COVID-19 PCR positive patients through April 28, 2020. Time-points of sequential implementation of key measures for the management of COVID-19 patients were recorded.ResultsA total of 1023 COVID-19 patients were hospitalized during the study period with 165 deaths (16 %). Case fatality rate during week one was 42% and down trended over time (Figure 1). Key measures were sequentially implemented over the course of the study period as shown in Figure 1. These included development and implementation of in-house PCR testing, dedicated infectious diseases COVID-19 rounding teams, treatment guidelines and algorithms, and early steroid use in hypoxic patients. Figure 2 demonstrates that despite the surge of COVID-19 admissions, mortality continued to improve over time.Figure 1. Trend line of all-cause in-house morality over time Figure 2. Mortality by admission date over time ConclusionMaturation effect takes into consideration that regardless of individual interventions, HCP improve their knowledge of the disease process and treatment over time leading to better outcomes. Our study shows the possibility of the maturation effect leading to improved survival in hospitalized COVID-19 patients. The maturation effect should be accounted for when evaluating the effect of specific interventions for COVID-19.DisclosuresMarcus Zervos, MD, Melinta Therapeutics (Grant/Research Support)

Factors Influencing Time from Initial Presentation to Start of Plasma Exchange (PEX) in Patients with Acute Thrombotic Thrombocytopenic Purpura (TTP)

Background: Acute Thrombotic Thrombocytopenic Purpura (TTP) is a life-threatening medical emergency and plasma exchange (PEX) is the only treatment shown to significantly impact acute mortality (Rock et al, N Engl J Med 1991). Diagnosis can be challenging and therein arrangements for PEX must be made, with most centers in the United Kingdom (UK) having to co-ordinate transfer to a tertiary site. To understand issues affecting practice the trainee research network HaemSTAR conducted a retrospective nationwide review of patients presenting to UK hospitals with TTP against British Society of Haematology clinical guidelines (Scully et al, B J Haem 2012). Analysis was conducted on the time from hospital presentation to initiation of treatment and impact on patient outcomes. Method: Adults ≥18 years presenting to hospital between 1st June 2014 and 1st June 2019 with first episode acute TTP and ADAMTS13 level &amp;lt;10% were identified by local clinicians. Anonymized data of baseline characteristics and treatment times was submitted via an online secure server. Time to PEX was defined as time from receipt of the first full blood count sample in the laboratory to time of plasma release for PEX from blood bank. Where patients were transferred between sites data was linked retrospectively. Results: Data on 148 patients treated at 80 UK hospitals was used for analysis (demographics table 1). 142 patients (96%) received PEX, 67 (47%) at site of presentation and 75 (53%) after hospital transfer. 6 patients died before receiving PEX. 37 patients (25%) received PEX within 8 hrs of hospital presentation, 91 patients (61%) within 24 hrs. 33 patients (22%) commenced PEX more than 48 hrs from presentation. The overall median time to PEX from initial presentation was 15 hours (95% CI 11.3-18.7). Availability of on-site PEX was associated with earlier treatment initiation with median time to PEX for those treated on site 10 hrs (95% CI 7.7-12.3) vs. 21 hrs (95% CI 16.8-25.2) for patients transferred. A blood film comment of red cell fragments significantly impacted time to treatment: in 24 cases with no fragments documented median time to PEX was 110 hrs (95% CI 39-181) vs. 10 hrs (95% CI 8.5-11.5) in cases where fragments were reported (fig 1). On univariate and multivariate analysis age &amp;lt;60 years, hemoglobin (Hb) &amp;lt;100 g/L, presence of fragments, PEX available on-site and admissions occurring after May 2017 were significant predictors for PEX initiation within 8 hrs. PEX within 24 hrs was associated with age &amp;lt;60 years, platelet count &amp;lt;30 x 109/L, Hb &amp;lt;100 g/L and presence of fragments only. The presence of cardiac and/or central nervous system (CNS) involvement was not predictive of time to initiation of PEX (table 1). 96 patients (62%) received steroids within 24 hrs of presentation, 98 of 128 patients with cardiac/CNS involvement (77%) received rituximab within 48 hrs and 12 patients (8%) received platelet transfusion in the absence of major bleeding. 19 patients (12%) died within 30 days of presentation (median time to death 10 days, range 0-23). In 7 of these cases (37%) a delay &amp;gt;24 hrs from presentation to diagnosis was reported despite presence of fragments in 4 cases. Mortality did not correlate with availability of on-site PEX. Discussion: This is the first multi-center record of time to treatment from initial presentation of acute TTP. Results comply with guidance for rapid initiation of PEX with 61% patients commencing within 24 hrs of presentation and, from June 2017, 34% of patients initiating PEX within 8 hrs. The recent increase in early PEX initiation correlates with initiatives to improve treatment pathway efficiency following diagnosis of TTP. Early use of steroids and rituximab correlated with earlier use of PEX indicating where timely diagnosis was made there was good compliance with guidelines. Inappropriate use of platelets appeared attributable to misdiagnosis. Older patients, those with higher platelet counts and Hb and absence of red cell fragments on film report were more likely to experience prolonged time to initiation of PEX. This does not appear related to PEX access, but most likely the difficulty of making TTP diagnosis in this cohort. That 22% of patients initiated PEX over 48 hrs from admission indicates the issue is relatively common and with several deaths occurring in this group we suggest initiatives to increase early diagnosis should be prioritised. Full contributor list: http://haemstar.org/flash-mob-audit-2019/ Disclosures McCulloch: Sanofi: Research Funding. Nicolson:Principia Biopharma: Research Funding; Novartis: Research Funding; Rigel pharmaceuticals: Research Funding; Bayer: Honoraria. Shaw:Octapharma: Research Funding. Scully:Alexion: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; Ablynx/Sanofi: Consultancy, Other: Advisory Board, Speakers Bureau; Shire/Takeda: Other: Advisory Board, Research Funding, Speakers Bureau; Novartis: Other: Advisory Board, Speakers Bureau.

P0573CLINICAL PRESENTATION AND OUTCOMES OF ACUTE INTERSTITIAL NEPHRITIS: A TEN YEARS' EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN KARACHI, PAKISTAN

Abstract Background and Aims Acute interstitial nephritis (AIN) is a potentially reversible, but relatively under-diagnosed cause of acute kidney injury. The effectiveness of steroids for treatment of AIN is debated. Data is scarce regarding the clinical presentation, use of steroids and its impacts on outcomes in AIN in our part of the world. The objective of our study was to study the clinical features, causes and outcomes of AIN and to evaluate the role of steroids in the management. Method We performed a retrospective study of 48 patients with biopsy proven AIN. Exposure was defined as the use of steroids. The main outcomes were recovery of renal function (Early (≤3 weeks) or Late (&amp;gt;3 weeks)) and hemodialysis dependence at 12 weeks Results 48 (4.9%) AIN cases were found among 978 renal biopsies performed from 2007-2018. Mean age was 47.6 ± 12.1 years. 56.3% were males. The offending agent was identified in 45.8% cases with NSAIDs (45.4%) being the most common, followed by antibiotics (22.7%), diuretics (9%), and PPI (4.5%). 75% presented with eGFR &amp;lt;15 ml/min/1.73m2 (n=36) out of which 58.3 % (n=21) needed hemodialysis. Mean proteinuria was 2.28 ± 0.99 g/day. 81.3% (n=39) patients received steroids out of which 39.6% were started on steroids after an initial period of observation after stopping the offending agent. Mean dose of prednisone was 0.8 ± 0.2 mg/kg per day. Mean time to steroid commencement was 14 ± 17.39 days. Early use of steroids (≤11 days after presentation) was significantly associated with earlier recovery (p= 0.009) as compared to late steroids (&amp;gt;11 days). A non-significant trend towards complete recovery (within 25% of baseline Creatinine) was noted in early steroid group (52.9%, n=17) vs “no steroid” (33.3%, n=9) or “late steroids” (10.5%, n=19) groups (p=0.208). 47.4% remained dialysis dependent on follow up with no difference made by steroid use (p=0.971). Conclusion Our data showed the benefit of earlier use of steroids in achieving rapid and complete renal recovery. Late steroid use was not associated with any further recovery of renal function at an additional risk of exposing patients to undue adverse effects. This is the first report from Pakistan documenting the tendency of nephrologists towards use of steroids for AIN.

Cancer Immunotherapy for Immunocompromised Patients: An Often Ignored, yet Vital Puzzle.

Dear Editor,I have read the recent issue of the Journal of Immunotherapy and Precision Oncology, edited by Dr. Joud Hajjar, with immense enthusiasm. It describes “Cancer immunotherapy in immunocompromised patients: An often ignored, yet very vital puzzle!”[1]These immunocompromised patients have a strikingly high susceptibility to develop a multitude of difficult-to-treat cancers.[2] I wish to expand on the imminent challenges and their pertinency in real-world practice.In the last decade, immunotherapy, especially immune checkpoint inhibitors (ICIs), has revolutionized the cancer care. Cancer armamentarium is widened with the advent of ICI and the current oncologic indications of ICI encompass melanoma, lung cancer, genitourinary cancer, breast cancer, head and neck cancer, Merkel cell carcinoma, and others.Notably, immunotherapeutic drugs are different from existing therapies in the mechanism of action, and there is a lack of cross-resistance. The recent evidence further emphasizes that immune evasion is important for carcinogenesis and certain arduous cancers preferentially develop in immunocompromised hosts.[2,3] The potential factors affecting this are the specific aspects of immune deficiency, the duration of immunosuppression, the immunomodulatory agents used, and the differences in patient populations. However, a more appealing and unique facet is the labyrinthine relationship between immunosuppression and cancer and their co-action with ICI agents driving the antitumor immune response.[2–4] Despite increasing indications and usage, we still have limited knowledge regarding the efficacy and safety in this exclusive immunosuppressed population as these patients are excluded from the clinical trials. Nonetheless, retrospective studies reported safe use of ICI in immunocompromised situations such as HIV infection or autoimmune disorders.[2,4,5] Some of the recent studies showed that ICIs are both safe and efficacious in HIV-positive patients with various malignancies, including Kaposi sarcoma, nonsmall cell lung cancer, melanoma, Merkel cell carcinoma, and Hodgkin's lymphoma.[2,4]Clinical trials are underway to provide robust answers for the safety and efficacy of ICI in this population. Per contra, literature on ICI use in transplant recipients is discordant, where there is a real threat of possibly lethal-transplant rejections as high as 40%, physicians should be wary using ICI in this unique, data-free zone.[6]Another similar population is patients on low-dose steroids for a variety of clinical conditions such as respiratory illnesses, fatigue, or brain metastasis. There is an argument against early or baseline use of steroids with ICI, which emerged from retrospective lung cancer cohorts.[7,8] In those cases, it is reasonable switching to alternative medications or decreasing corticosteroid dose (&lt;10 mg) if feasible, recognizing that patients who are receiving steroids typically have more aggressive and extensive disease, which represents a possible confounding effect when interpreting these data. In contrast, late use of steroids in the treatment course may confer improved outcomes, perhaps reflecting the evidence linking immune-related adverse events and efficacy of ICI.[9,10]I highly commend Dr. Hajjar for lighting up this crucial and often ignored controversy![1]

Outcome of Bell’s Palsy- An Institutional Study

Background and purpose: Bell’s palsy represents sudden onset of lower motor neuron type of facial palsy in the absence of other cranial nerve involvement. Pathophysiologically, it has been described mostly due to viral infection, and early use of antiviral therapy, steroids and physiotherapy has shown to limit the disease and helps in early recovery from palsy. With the objective to evaluate over all clinical outcome of the patients presented with Bell’s palsy with our treatment strategies this study was performed. &#x0D; Material and method: This is a prospective analytical study with non probability consecutive sampling technique over the duration of 6 months. Continuous variable like age is presented using mean and standard deviation. Categorical data are presented as percentage and analysis of outcome of the treatment is done using Fischer’s exact test. Statistical analysis was done using SPSS -20.&#x0D; Result: Total number of patients enrolled in the study was 19, where mean age was 33.47 (SD 15.71) years. Bell’s palsy was more commonly seen in female patients (58%). House Brackmann grading of facial nerve palsy at the time of presentation was four. There was significant association of early treatment with complete recovery in this study.&#x0D; Conclusion: Early treatment of bells palsy with acyclovir, steroids, and physiotherapy has shown promising result in most of the studies; and this holds true in this study as well, where delaying the treatment was significantly associated with poorer recovery.

Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma

Earlier Steroid Use with Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Large B Cell Lymphoma

Letter: When Less is More: Dexamethasone Dosing for Brain Tumors.

Letter: When Less is More: Dexamethasone Dosing for Brain Tumors.

PS1067 AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B CELL LYMPHOMA: PRELIMINARY RESULTS OF EARLIER STEROID USE

Background:Axicabtagene ciloleucel (axi‐cel) is an autologous anti‐CD19 chimeric antigen receptor (CAR) T cell therapy approved in the European Union and United States for patients with relapsed/refractory large B cell lymphoma with ≥ 2 prior systemic therapies. In the 2‐year follow‐up of ZUMA‐1, the objective response rate was 83% with a complete response rate of 58%. Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 11% and 32% of patients, respectively; 26% of patients received steroids, and 43% received tocilizumab (Locke et al. Lancet Oncol. 2019). A safety expansion cohort was added to evaluate the effect of earlier steroid use on the rates of these adverse events (AEs).Aims:To assess the impact of early steroid use on outcomes in patients treated with axi‐cel.Methods:Eligible patients with relapsed/refractory large B cell lymphoma were leukapheresed and received conditioning chemotherapy followed by a target dose of 2 × 106 anti‐CD19 CAR T cells/kg. Patients in this cohort received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoint for this cohort was incidence and severity of CRS and NE.Results:As of September 14, 2018, 21 of 40 planned patients received axi‐cel with a minimum follow‐up of 1 month (median, 2.6 months). The median age was 63 years (range, 36 – 73), 67% were male, 81% had disease stage III‐IV, 76% were relapsed/refractory to ≥ second‐line therapy, and 10% had relapsed post‐autologous stem cell transplantation. Seventy‐six percent of patients received steroids and 81% received tocilizumab. Most patients (81%) had Grade ≥ 3 AEs, most commonly neutrophil count decreased (33%), anemia (29%), and pyrexia (24%). Grade ≥ 3 NE occurred in 10% of patients; the most common symptoms were somnolence (10%) and confusional state (10%). Grade 1 and 2 NE occurred in 38% and 5% of patients, respectively. No patient had Grade ≥ 3 CRS; 33% of patients had Grade 1 CRS and 67% had Grade 2. There were no deaths due to AEs; 1 patient died due to disease progression. The objective response rate per investigator assessment was 76% with 48% of patients achieving a complete response. Pharmacokinetic data will be presented.Summary/Conclusion:Early use of steroids may help in managing severe CRS and NE by potentially reducing their incidence in patients treated with CAR T cell therapy without affecting response rates. Optimizing AE management may help to further improve the benefit:risk profile of CAR T cell therapy.

Preliminary results of earlier steroid use with axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL).

7558 Background: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved in the EU and US for patients (pts) with R/R LBCL with ≥ 2 prior systemic therapies. In the 2-y follow-up of ZUMA-1, the objective response rate (ORR) was 83% with a complete response (CR) rate of 58%. Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 11% and 32% of pts, respectively; 26% of pts received steroids, and 43% received tocilizumab (Locke et al. Lancet Oncol. 2019). A safety expansion cohort was added to evaluate the effect of earlier steroid use on the rates of these adverse events (AEs). Methods: Eligible pts with R/R LBCL were leukapheresed and received conditioning chemotherapy followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg. Pts in this cohort received early steroid intervention starting at Grade 1 NE and at Grade 1 CRS when no improvement was observed after 3 days of supportive care. The primary endpoint for this cohort was incidence and severity of CRS and NE. Results: As of 9/14/2018, 21 of 40 planned pts received axi-cel with a minimum follow-up of 1 mo (median, 2.6 mo). The median age was 63 y (range, 36 – 73), 67% were male, 81% had disease stage III-IV, 76% were R/R to ≥ second-line therapy, and 10% had relapsed post-autologous stem cell transplantation. Seventy-six percent of pts received steroids and 81% received tocilizumab. Most pts (81%) had Grade ≥ 3 AEs, most commonly neutrophil count decreased (33%), anemia (29%), and pyrexia (24%). Grade ≥ 3 NE occurred in 10% of pts; the most common symptoms were somnolence (10%) and confusional state (10%). Grade 1 and 2 NE occurred in 38% and 5% of pts, respectively. No pt had Grade ≥ 3 CRS; 33% of pts had Grade 1 CRS and 67% had Grade 2. There were no deaths due to AEs; 1 pt died due to disease progression. The ORR per investigator assessment was 76% with 48% of pts achieving a CR. Pharmacokinetic data will be presented. Conclusions: Early use of steroids may help in managing severe CRS and NE by potentially reducing their incidence in pts treated with CAR T cell therapy without affecting response rates. Optimizing AE management may help to further improve the benefit:risk profile of CAR T cell therapy. Clinical trial information: NCT02348216.

Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors

BackgroundSteroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs.MethodsWe reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation.ResultsOut of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation.ConclusionsIn patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.