Steroid Prophylaxis Research Articles

Pathohistological Changes in the Lungs of Very Preterm Infants with Bronchopulmonary Dysplasia Depending on the Clinical Features.

Establishing clinical factors associated with histological changes in the lungs of very preterm infants with evolving or established bronchopulmonary dysplasia (BPD) is essential for the development of more effective preventive interventions. Thirty-two infants with a gestational age (GA) of <32 weeks who died of BPD or had BPD but died due to other causes were included in the study. The associations of clinical data with histopathological changes in the lungs were assessed. The mean (standard deviation) GA of infants was 26.7 (1.9) weeks, and the mean birth weight was 919.7 (242.9) g. We revealed significant associations of maternal smoking with vascular hypertension lesions (r s = 0.5, p < 0.05) in infants' lungs. Intrauterine growth retardation increased the risk of extensive fibroproliferation (r s = 0.4, p < 0.05). In infants with patent ductus arteriosus (PDA) requiring treatment, muscle hyperplasia (r s = 0.5, p < 0.05) was detected more often. The longer duration of mechanical ventilation (MV) correlated with diffuse interstitial fibroproliferation (r s = 0.5, p < 0.05), airway epithelial lesions (r s = 0.3, p < 0.05), and airway muscle hyperplasia (r s = 0.4, p < 0.05). In infants who needed the longer MV and/or oxygen supplementation, an increased incidence of extensive fibroproliferation was found (r s = 0.4 and r s = 0.4 respectively, p < 0.05). Antenatal steroids decreased the incidence of diffuse interstitial fibrosis (r s = - 0.4, p < 0.05). In very preterm infants with a GA of less than 32 weeks, lack of antenatal steroid prophylaxis, intrauterine growth restriction, presence of hemodynamically significant PDA, and prolonged MV or oxygen supplementation are associated with the pathomorphological lung changes that are more typical for "old" BPD. Traditional preventive measures against BPD remain essential in a modern population of very preterm infants. · Pathomorphological lung changes correlate with clinical data in very preterm infants who died of BPD.. · Lack of antenatal steroids prophylaxis, growth retardation, PDA, and prolonged mechanical ventilation affect lungs.. · Traditional BPD preventive measures remain essential in the modern population of preterm infants..

The effect of an additional pre-extubational loading dose of caffeine citrate on mechanically ventilated preterm infants (NEOKOFF trial): Study protocol for a multicenter randomized clinical trial.

Minimizing the duration of mechanical ventilation is one of the most important therapeutic goals during the care of preterm infants at neonatal intensive care units (NICUs). The rate of extubation failure among preterm infants is between 16% and 40% worldwide. Numerous studies have been conducted on the assessment of extubation suitability, the optimal choice of respiratory support around extubation, and the effectiveness of medical interventions. Since the Caffeine Therapy for Apnea of Prematurity (CAP) trial, caffeine has become one of the essential drugs at NICUs. However, the optimal dosage and timing for adequate effectiveness still need to be more conclusive. Previous studies suggest that higher doses of caffeine treatment increase the success rate of extubation. Therefore, we aim to determine whether using a single additional loading dose of caffeine citrate one hour prior to extubation impacts the success rate of extubation. The study is an open-label, multicenter randomized clinical trial testing the effectiveness and safety of pre-extubational loading dose of caffeine citrate. Inclusion criteria will be infants born before the 32nd gestational week, before the first extubation attempt after at least 48 hours of mechanical ventilation, and a signed parental informed consent. A total of 226 patients will be randomly allocated to either the experimental or control group. The randomization will be stratified by gestational age and antenatal steroid prophylaxis. Preterm infants in the experimental group will receive an additional intravenous (IV) loading dose (20 mg/kg) of caffeine citrate one hour before the first planned extubation, in addition to the standard dosing regimen (20 mg/kg caffeine citrate IV on the first day of life and 5 to 10 mg/kg IV or orally caffeine citrate each consecutive day). Preterm infants in the control group will receive the standard dosing regimen. The primary outcome will be reintubation within 48 hours. A pre-extubational loading dose of caffeine citrate can reduce extubation failure. Obtaining evidence on this feature has the potential to contribute to finding the optimal dosing regimen. The study protocol was approved by the Hungarian Ethics Committee for Clinical Pharmacology of the Medical Research Council and National Institute of Pharmacy and Nutrition (OGYÉI/6838-11/2023). ClinicalTrials.gov identifier NCT06401083 Registered 06. May 2024.; EudraCT number: 2022-003202-77.

Treatment of Hyperthyroidism in Graves' Disease Complicated by Thyroid Eye Disease.

Thyroid eye disease (TED) is the most consequential extrathyroidal manifestation or complication of Graves' disease (GD). Treatment of hyperthyroidism in GD complicated by TED is challenging. Antithyroid drugs (ATDs) and thyroidectomy do not change the natural course of TED, while radioactive iodine (RAI) is associated with a small but well-documented risk of TED de novo occurrence or its progression/worsening. In the presence of mild TED, any treatment for hyperthyroidism can be used, but should RAI treatment be selected, steroid prophylaxis (short course of low-dose prednisone) is strongly recommended if TED is of recent onset and/or risk factors for progression exist. In moderate-to-severe and active TED, ATDs are the preferred treatment but thyroidectomy is a valid option. RAI ablation is generally avoided, but it might be used when the clinical situation calls for it but with extreme caution if an aggressive treatment for TED with high-dose glucocorticoids (with or without orbital radiotherapy) is administered concomitantly. In moderate-to-severe and inactive TED, all three treatments for hyperthyroidism are acceptable, and steroid prophylaxis in RAI-treated patients should be given when risk factors for TED progression are identified. Management of sight-threatening TED represents the absolute priority, and hyperthyroidism should be controlled with ATDs until TED has been cured.

Association between tumor location and toxicity outcomes after stereotactic radiosurgery for brain metastases.

Toxicities associated with stereotactic radiosurgery (SRS) are important when considering treatment and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and risk of toxicity after SRS. We conducted a retrospective institutional review of patients treated with SRS for brain metastases between 2008 and 2023. Outcomes included radiation necrosis, seizure, local failure, and overall survival (OS). We reviewed 215 patients treated to 605 metastases (median diameter 10mm, IQR 5-17 mm), in the frontal (34%), cerebellar (19%), parietal (16%), temporal (13%), and occipital (13%) regions. Median follow-up was 16 months (IQR 7-36). New-onset seizures developed in 11% (19/174) of patients without prior seizure and was higher in patients with motor or sensory cortex lesions (12/48, 25%) on multivariate analysis (MVA, P = 0.02). SRS-related grade ≥ 2 symptomatic radionecrosis occurred in 6% (33/605) of lesions and correlated with larger metastasis volume (P < 0.001) and renal cell carcinoma histology (P < 0.05), while supratentorial location was nearly significant (MVA, P = 0.06). Median OS across all patients was 16 months (95% CI 12-20). Patients with symptomatic radiation necrosis had a longer median survival compared to those who did not (43 vs. 14 months, P = 0.002), which remained significant alongside Karnofsky performance status and extracranial disease on MVA. Brain metastasis location in the motor or sensory cortex is associated with increased risk of new-onset seizure following SRS and may warrant consideration of steroid and/or anti-epileptic prophylaxis. Symptomatic radiation necrosis is uncommon in the cerebellum and may be increasing with improvements in survival.

Steroid Prophylaxis in Patients Receiving CAR T-Cell Therapy for Relapsed and Refractory Non-Hodgkin Lymphoma

Steroid Prophylaxis in Patients Receiving CAR T-Cell Therapy for Relapsed and Refractory Non-Hodgkin Lymphoma

Prediction of post-ESD esophageal stricture by a nomogram and risk factor analysis of ineffective oral steroids prophylaxis

Background and aimsSeveral risk models for esophageal stricture after endoscopic submucosal dissection have been developed. However, some of them did not include the use of steroids in the risk analysis. Glucocorticoid sensitivity mediated by glucocorticoid receptor expression has not been discussed in this condition.MethodsClinical and endoscopic characteristics were included in the logistic regression model to establish a nomogram for stenosis prediction. The score for each risk factor was estimated. Risk factors of ineffective oral steroid prophylaxis were analyzed and glucocorticoid receptor expressions were detected by immunohistochemistry.ResultsThree hundred fourteen patients of endoscopic submucosal dissection for esophageal superficial neoplasms were included to develop the nomogram. The circumferential range(≤ 3/4, 3/4–1 or the whole circumference), longitudinal diameter reached 4 cm (yes or not) and lesion location (the cervical and upper thoracic part, the middle thoracic part or the lower thoracic part) consisted of the nomogram. Patients have a high risk of esophageal stricture if they have a total point greater than 36. In the simplified risk score model, the corresponding cutoff score was 1. 92 patients with oral steroid prophylaxis were separately analyzed and the circumferential mucosal defect involving 7/8 or more was an independent risk factor of ineffective prevention (OR 12.2, 95%CI 5.27–28.11). The expression of glucocorticoid receptor β was higher in the stricture group (p = 0.042 for AOD; p = 0.016 for the scoring system).ConclusionsWe established a nomogram for esophageal stricture prediction. Depending on the characteristics of lesions, it is possible to estimate the risk of stricture under routine post-ESD treatments (no steroids or oral steroids). Alternative treatments should be considered if the risk is extremely high, especially for patients with mucosal defects involving 7/8 or more of circumference in which oral steroid treatment tends to be ineffective. The higher glucocorticoid receptor β may indicate potential glucocorticoid resistance.

Predictors of stricture after endoscopic submucosal dissection of the esophagus and steroids application.

Endoscopic submucosal dissection (ESD) is a reliable method to resect early esophageal cancer. Esophageal stricture is one of the major complications after ESD of the esophagus. Steroid prophylaxis for esophageal strictures, particularly local injection of triamcinolone acetonide (TA), is a relatively effective method to prevent esophageal strictures. However, even with steroid prophylaxis, stenosis still occurs in up to 45% of patients. Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients. To identify the predictors of esophageal strictures after steroids application. Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion- and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study. The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis. A total of 120 patients were included in the analysis. In the oral prednisone and oral prednisone combined with local tretinoin injection groups, the stenosis rates were 44/53 (83.0%) and 56/67 (83.6%), respectively. Among them, univariate analysis showed that the lesion circumference (P = 0.01) and submucosal injection solution (P = 0.04) showed significant correlation with the risk of stenosis formation. Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports, such as additional chemoradiotherapy and tumor location. We identified a lesion circumference < 5/6 (OR = 0.19; P = 0.02) and submucosal injection of sodium hyaluronate (OR = 0.15; P = 0.03) as independent predictors of on esophageal stricture formation. Steroid prophylaxis effectively prevents stenosis. Moreover, the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures. Additional interventions should be considered in high-risk patients.

Phase 1 Study of JNJ-81201887 Gene Therapy in Geographic Atrophy Secondary to Age-Related Macular Degeneration

ObjectiveTo evaluate the safety and tolerability of a single intravitreal injection of JNJ-81201887 (JNJ-1887) in patients with geographic atrophy (GA) secondary to advanced dry age-related macular degeneration (AMD). DesignPhase 1, open-label, single-center, first-in-human clinical study. SubjectsAdult patients (aged ≥50 years) with GA secondary to AMD in the study-treated eye (treated eye) with a best corrected visual acuity (BCVA) Snellen equivalent of 20/200 or worse in the treated eye (20/80 or worse after the first 3 patients), a total GA lesion size between 5 and 20 mm2 (2-8 disc area), and BCVA of 20/800 or better in fellow, non-treated eye were included. MethodsPatients (N=17) were sequentially enrolled into low (3.56×1010 viral genome [vg]/eye; n=3), intermediate (1.07×1011 vg/eye; n=3), and high (3.56×1011 vg/eye; n=11) dose cohorts without steroid prophylaxis and assessed for safety and tolerability over 24 months. Main Outcome MeasuresSafety and tolerability outcomes included assessment of ocular and non-ocular treatment-emergent adverse events (AEs) over 24 months. Secondary outcomes included GA lesion size and growth rate. ResultsBaseline patient characteristics were consistent with the disease under study, and all enrolled patients had foveal center–involved GA. JNJ-1887 was well tolerated across all cohorts, with no dose-limiting AEs. There were no serious or systemic AEs related to study intervention. Overall, 5/17 (29%) patients experienced 6 events of mild ocular inflammation related to study treatment; exam findings in all resolved, and AEs resolved in 4 of 5 patients following topical steroids or observation. One unresolved vitritis event, managed with observation, occurred in a patient with an unrelated fatal AE. No endophthalmitis or new-onset choroidal neovascularization was reported. GA lesion growth rate was similar among all cohorts over 24 months. For treated eyes in the high-dose cohort, GA lesion growth rate showed continued decline through 24 months, with a reduction in mean square root lesion growth from 0.211 mm at months 0-6 to 0.056 mm at months 18-24. ConclusionsAll 3 studied doses of JNJ-1887 had a manageable safety profile through 24 months of follow-up. Further investigation of JNJ-1887 for the treatment of GA is warranted.

Phase 1 study (NCT04931823) of CPO100 (albumin bound docetaxel) in patients with advanced solid tumors.

3027 Background: Docetaxel (Taxotere) is a widely used taxane; the use of docetaxel may have been limited by its original formulation, which contributes to multiple severe adverse effects. Polysorbate-80 in the current formulation has been implicated in several systemic reactions (e.g., hypersensitivity, nonallergic anaphylaxis, rash) and injection- and infusion-site adverse events (pain, erythema, thrombophlebitis). By eliminating polysorbate-80, the use of steroids at the time of infusion may also be eliminated. To improve the safety profile and enhance tumor-targeted drug exposure, CPO-100, an albumin-bound docetaxel formulation without polysorbate-80 was developed. This Phase 1 dose escalation study assessed the maximum tolerated dose (MTD), pharmacokinetics (PK), safety, and efficacy of CPO-100 administered without steroid pretreatment in a weekly schedule (3 weekly doses/ 1-week rest). Methods: Patients (pts) were enrolled in a modified 3 x 3 design starting at doses of 6 mg/m2 and ranging up to 50 mg/m2 on the weekly schedule (WS). At each visit, safety was assessed. PK data was collected on days 1, 8 and 15 of cycle 1. Efficacy was assessed every 2 cycles (8 weeks) until progression or treatment discontinuation. The MTD was determined with and without the use of granulocyte colony stimulating factor (GCSF) in cycle 1. Results: Thirty-four pts with various solid tumors were enrolled. Prior regimens: 2 to 17 (median 4). Prior exposure to taxanes: 18 pts (53%). The most common adverse events (AEs) were fatigue (N=19), nausea (N=18) and anemia (N=15). Grade 3/4 neutropenia (as a term or laboratory finding) for doses above 35 mg/m2 was 60%. Serious AEs (SAEs) occurred in 13 pts; SAEs regardless of relationship in more than 1 pt were pleural effusion, hypotension and pneumonia. For all evaluable pts, the overall response rate was 2/30 (7%) with two PRs observed in pts with breast and nasopharyngeal cancers. The disease control rate (DCR) was 60%. Among the 18 pts with SD or better, the median (K-M estimate) duration was approximately 10.9 months (mos; range 1.7 to 11.1 mos). A linear relationship between plasma concentrations of total docetaxel and dose was observed. The half-life of total docetaxel ranged from 13 to 39 hrs. Slight accumulation was observed on WS, and steady state was achieved after the second dose. Conclusions: Preliminary data with CPO-100 administered on a weekly basis shows potential efficacy in heavily pretreated pts, especially with prior taxane exposure, with a tolerable WS. With a similar dose, CPO-100 demonstrated a better safety profile than docetaxel. The most prominent concern is manageable neutropenia, especially on a dose above 35 mg/m2, where GCSF supplementation was needed. Further development is warranted, including combinations with agents such as PD-1/PD-L1 inhibitors that might benefit from absence of steroid prophylaxis. Clinical trial information: NCT04931823 .

Abstract CT243: Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL)

Abstract Background: R/R FL is an incurable disease and outcomes worsen with successive relapses. A high unmet need remains for therapies that improve tumor control and extend survival after relapse. Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, demonstrated compelling efficacy, generally manageable safety, and maintenance of pt-reported overall quality of life scores from baseline in an interim analysis of the ELM-2 study (NCT03888105) in heavily pretreated pts with R/R FL (Villasboas et al. ASH 2023). Here, for the first time, we present the primary analysis of R/R FL in ELM-2. Methods: IV odronextamab was administered in 21-day cycles (C) until disease progression/unacceptable toxicity. Steroid prophylaxis and step-up dosing (0.7/4/20 mg) were used in C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 80 mg on Days (D) 1, 8, and 15 of C2-4. Maintenance dosing continued at 160 mg Q2W, or Q4W if complete response (CR) was durable for 9 months (mo). Primary endpoint was objective response rate (ORR) per Lugano criteria by independent central review (ICR). Secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Primary analysis was performed when 128 pts had ≥52 weeks’ follow-up. Results: At data cutoff (Oct 20, 2023), 128 pts with FL Grade (Gr) 1-3a were evaluable for efficacy and safety: median age 61 yrs (range 22-84); FLIPI risk score 3-5 57.8%; POD24 49.2%; median 3 prior lines of therapy (2-13); 71.9% refractory to last treatment (Tx); 74.2% refractory to an anti-CD20 antibody. The median no. of Tx cycles was 19.4 (0.1-95.9); 95.3% and 85.2% of pts completed C1 and C4, respectively.Median efficacy follow-up was 20.1 mo; ORR was 80.5% and CR rate was 73.4% confirmed by ICR. Responses were durable (median DOR 22.6 mo; median DOCR 25.1 mo). Median PFS was 20.7 mo and 24-mo PFS was 46.1%. Median OS was not reached and 24-mo OS was 70.1%.The odronextamab safety profile was generally manageable and consistent with previous reports. Tx-emergent adverse events (AEs) occurred in all pts (Gr ≥3 85.9%); 15.6% had AEs leading to Tx discontinuation. With 0.7/4/20 mg step up (n=60), CRS events were mostly low grade (Gr 1 45.0%; Gr 2 10.0%; Gr 3 in 1 pt), occurred mostly in C1, and resolved in a median of 2 days; ICANS was reported in 1 pt (Gr 2). Infection rates were consistent with heavily pretreated, immunosuppressed pts (Leonard et al. JCO 2019; Hayne et al. BBMT 2020), occurring in 79.7% (102/128) of pts (Gr 4/5 14.0%; COVID-19 36.7% [Gr 5 6.3%]).Conclusion: Odronextamab demonstrated deep and durable responses in heavily pretreated pts with R/R FL; 91% of responders achieved CR, correlating with favorable PFS and OS at 24 mo. Odronextamab had a generally manageable safety profile and a low incidence of Gr 3 CRS/ICANS. Odronextamab could offer an important off-the-shelf Tx option for pts with heavily pretreated R/R FL. Citation Format: Geoffrey Chong, Michal Taszner, Silvana Novelli, Seok-Goo Cho, Jose C. Villasboas, Ana Jiménez Ubieto, Benoît Tessoulin, Michelle Poon, David Tucker, Jan Walewski, Yuqin Song, Emmanuel Bachy, Stephanie Guidez, Aranzazu Alonso, Deepa Jagadeesh, Stefano Luminari, Laura Magnano Mayer, Elżbieta Iskierka-Jażdżewska, Monica Tani, Jingxian Cai, Amulya Uppala, Saleem Shariff, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Tae Min Kim. Primary analysis of the Phase 2 ELM-2 study: Odronextamab in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT243.

COVID-19 vaccination and corneal allograft rejection- a review.

To provide a comprehensive literature review on the perceived correlation between COVID-19 vaccination and corneal allograft rejection, and to characterize risk factors, time course, graft outcomes and proposed immunological basis. A literature review was conducted in August 2023 using 4 electronic databases: PubMed, EMBASE, MEDLINE and Scopus. Articles were sourced using key words associated with COVID-19 vaccination and corneal graft. All articles were screened for relevance by abstract review. Duplicates and articles related to COVID-19 infection were excluded. No time limits were set. Additional literature searches regarding cause of corneal graft rejection, rates of graft rejection associated with other vaccines and the cellular mechanism of rejection were also performed. 262 articles were identified from the literature search. 37 papers were included in the analysis based on defined inclusion criteria. This consisted of systematic reviews (n=6), review articles (n=5), retrospective studies (n=3), case series (n=8), letter to the editor (n=1) and case reports (n= 14). The majority of reported allograft rejections were in penetrating keratoplasties. Risk factors for COVID-19 vaccination associated rejection were previous allograft rejection episodes, repeat grafts and penetrating keratoplasty. Most reported rejection episodes were mild and resolved with treatment. Notably, several studies reported nil increase in corneal allograft rejection episodes over the COVID-19 vaccination period. Rejection episodes are associated with a broad spectrum of other vaccines and the complete pathophysiology is undetermined. Corneal allograft rejection appears to be a rare complication of COVID-19 vaccination most frequently observed in high-risk corneal transplants. The true extent of this correlation remains controversial; however, clinician awareness of this risk is essential to its mitigation. Patient counselling around symptom monitoring following vaccination and discussion around topical steroid prophylaxis may be prudent.

Thyroid Eye Disease: Epidemiology, Natural History, and Risk Factors.

Thyroid eye disease (TED) is an autoimmune disorder of the orbit and the most frequent extrathyroidal manifestation of Graves' disease but it may rarely occur in euthyroid/hypothyroid patients with chronic autoimmune thyroiditis. TED is a relatively infrequent disorder, particularly in its severe forms. Men tend to have more severe TED at an older age. The prevalence of TED is lower than in the past among patients with recent onset Graves' hyperthyroidism, and moderate-to-severe forms requiring aggressive treatments are no more than 5% to 6% of all cases. After an initial inflammatory (active) phase and a plateau phase, TED stabilizes and eventually inactivates (inactive or burnt-out phase) after an estimated period of 18-24 months. Minimal-to-mild TED often remits spontaneously, but complete restitutio ad integrum almost never occurs when TED is more than mild. Several risk factors contribute to its development on a yet undefined genetic background. Cigarette smoking is the most important of them, but thyroid dysfunction (both hyper- and hypothyroidism), radioactive iodine therapy (if not accompanied by low-dose steroid prophylaxis), elevated thyrotropin receptor antibodies, and, probably, hypercholesterolemia represent relevant modifiable risk factors. Early diagnosis, control and removal of modifiable risk factors, and early treatment of mild forms of GO (local treatment and selenium) may effectively limit the risk of progression to more severe forms.

Health-Related Quality of Life and Symptoms in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated with Odronextamab Monotherapy in the Phase 2 ELM-2 Study

Background. Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have poor prognosis and significant impairment of health-related quality of life (HRQoL). CD20xCD3 bispecific antibodies show promise in the management of R/R DLBCL. ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study of the CD20xCD3 bispecific antibody odronextamab, demonstrated deep and durable responses and generally manageable safety in patients with R/R DLBCL. We report herein, for the first time, patient-reported outcome (PRO) results for patients in the R/R DLBCL cohort in ELM-2. Methods. In ELM-2, patients with R/R DLBCLafter 2 or more prior lines of therapy received odronextamab IV weekly in 21-day cycles in Cycles (C) 1-4. Revisions to the step-up dosing regimen to mitigate cytokine release syndrome (CRS) were reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 160 mg on Days 1, 8, and 15 of C2-4 (the DLBCL 160 mg cohort). After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response for ≥9 months transitioned to dosing every 4 weeks. PRO data were collected via the FACT-Lym, EORTC QLQ-C30, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks in the first year and every 12 weeks in the second year. Pre-specified PRO analyses reported here are FACT-Lym lymphoma symptoms (LymS), FACT-G total, Trial Outcome Index (TOI), FACT-Lym total, EORTC QLQ-C30 general health status/quality of life (GHS/QoL), and EQ-5D-3L visual analog scale (VAS). PRO longitudinal analysis using mixed models for repeated measures (MMRM) were conducted through Week 42, the last visit with ≥10 patients with PRO data, and changes from baseline were statistically significant if the 95% confidence interval did not contain zero. No adjustment for multiplicity was performed, hence all statistical significance is nominal. Published ranges for minimum important difference (MID) for clinically meaningful thresholds are: GHS/QoL, 10; LymS, 2.9-5.4; FACT-G total, 3-7; TOI: 5.5-11; FACT-Lym total, 6.5-11.2; and EQ-5D-3L VAS, 7-12. Responder analysis and time to definitive deterioration (TTDD) used the upper end of these MID ranges to define clinically meaningful changes. Results. The final analysis of the DLBCL 160 mg cohort in ELM-2 assessed 141 patients. Median age was 66.0 (range, 24-88) years, with 56.0% ≥65 years, 59.6% male, 43.3% White, 47.5% Asian, 32.6% ECOG=0, and 67.4% ECOG=1. Median duration of follow-up was 26.2 (range, 8.5-34.3) months. PRO completion rates for FACT-Lym, EORTC QLQ-C30, and EQ-5D-3L were high at baseline and for most assessments through Week 42. Patients reported statistically significant and clinically meaningful improvements from Weeks 10 through 42 for FACT-Lym LymS (Figure), and from Weeks 18 through 42 for FACT-G total, FACT-Lym TOI, and FACT-Lym total (except Week 34 for FACT-G total and FACT-Lym total). Additionally, patients reported statistically significant and clinically meaningful improvements for EORTC QLQ-C30 GHS/QoL at Week 42, and for EQ-5D-3L VAS at Week 26. In responder analyses, the proportion of patients reporting clinically meaningful improvement or stability was higher than the proportion reporting meaningful worsening at each assessment through Week 42 for all scales/summary scores. Median TTDD was not reached for FACT-Lym LymS, FACT-Lym TOI, or EQ-5D-3L VAS. Conclusions. In the Phase 2 ELM-2 study, patients with R/R DLBCL reported favorable HRQoL during odronextamab treatment; patient-reported symptoms, functioning, and overall quality of life were maintained or improved from baseline through Week 42. Odronextamab treatment until disease progression may have benefits on HRQoL for heavily pretreated patients with R/R DLBCL and potentially addresses unmet needs in a challenging treatment setting. Collection of PROs was consistently high and the results offer important patient-centered insights into the overall benefit-risk profile of odronextamab in R/R DLBCL.

Radioactive iodine treatment for Graves' hyperthyroidism: incidence of Graves orbitopathy.

There are limited recent data on the effect of radioactive iodine (RAI) for Graves' disease on Graves' orbitopathy (GO) development or reactivation. This audit investigates the GO incidence in patients with Graves' disease after RAI treatment, and explores risk factors present, and steroid prophylaxis use. A retrospective audit of Graves' disease patients treated with RAI over a 5-year period. Data collected: smoking status, thyroid-stimulating hormone receptor antibody (TRAb) status, GO history, Graves' disease duration, eye features pre- and post-treatment, prophylactic corticosteroids, RAI dose given, post-RAI thyroid status, duration until hypothyroid. One hundred one patients were included, with a median Graves' disease duration 36 months. 34/101 (33.7%) were active/ex-smokers, 86/101 (85.1%) were TRAb-positive, 11/101 (10.9%) had a GO history; 32 (31.7%) had eye features present. Median RAI dose given was 596MBq. 8/101 (7.9%) patients received prophylactic corticosteroid; 89/101 (88.1%) achieved hypothyroid state in the year after RAI. GO developed in 5/101 (5.0%), of which 4/5 (80%) were de novo in high-risk individuals who did not receive steroids. One was a GO reactivation despite steroids. Two required intravenous steroids with/without orbital radiotherapy, one completed oral steroid taper; the remainder were treated conservatively. Our cohort had a lower GO incidence in patients with Graves' disease receiving RAI, with majority arising de novo . It is essential that all patients are assessed for Graves orbitopathy risk factors and counselled adequately prior to RAI. The decision to initiate steroids should be undertaken in a multi-disciplinary setting involving endocrinologists and ophthalmologists.

Multicenter Retrospective Evaluation of Treatment of High-Risk Acute Promyelocytic Leukemia (APL): Results from the Hematology Research Outcomes (HERO) Consortium

Background: Regimens employing all-trans retinoid acid and arsenic (ATRA+ATO) are the backbone of high-risk APL treatment. The APML4 regimen consists of a three-phase treatment approach: induction with ATRA, ATO, and idarubicin; two cycles of consolidation with ATRA+ATO; and maintenance with ATRA, methotrexate, and mercaptopurine. 1 MD Anderson Cancer Center (MDACC) developed a regimen incorporating gemtuzumab ozogamicin (GO) in addition to ATRA+ATO. 2 Differences in tolerability and efficacy between these two approaches are unknown as no comparative data exists. We aimed to describe real-world treatment outcomes for high-risk APL, comparing toxicity between APML4 and ATRA+ATO+GO. Methods We conducted a multicenter, retrospective cohort study including patients treated among six US centers participating in the pharmacist-led collaborative research consortium, HERO. Adults (&amp;gt;18 years) with newly diagnosed high-risk APL (t(15;17)(q24.1;q21.2)) according to the Sanz risk model 3 between April 2014 and June 2022, who received at least one dose of an induction regimen under the institution's high-risk protocol were compared based on induction regimen received. Patients with incomplete records were excluded. The primary endpoint was a composite of mortality, ICU admission, or confirmed infection during induction. Secondary endpoints included individual components of the primary endpoint, other induction-related toxicities, and complete response (CR) rate after induction. Analyses were performed as intent-to-treat which included all patients who received APML4 and ATRA+ATO+GO inductions regardless of consolidation strategies. Chi-square or Fisher's exact tests were utilized to evaluate dichotomous variables. Continuous variables were analyzed via Student's t-test or Mann-Whitney U test. Kaplan-Meier analysis with log-rank test was performed to estimate progression-free survival (PFS) and overall survival (OS). Results Fifty-seven patients with high-risk APL who started either APML4 (n=41) or ATRA+ATO+GO (n=16) as induction treatment met inclusion criteria. Baseline characteristics were balanced (Table 1) except for race and ethnicity, with a higher percentage of non-Hispanic white patients in the APML4 cohort (p=0.020) and a higher percentage of Hispanic/LatinX in the ATRA+ATO+GO cohort (p=0.011). Of evaluated molecular abnormalities, FLT3-ITD was most common (76%). Steroid prophylaxis was more common in the ATRA+ATO+GO cohort (p=0.015). Additional cytoreductive therapy was frequent in both arms: hydroxyurea used more often in the APML4 cohort (p=0.033) and idarubicin in the ATRA+ATO+GO cohort (p&amp;lt;0.001) (Table 1). Induction mortality was 7%, including 3 deaths in the APML4 cohort and 1 in the ATRA+ATO+GO (Table 2; p=1.000). Time to platelet recovery was longer with APML4 than ATRA+ATO+GO (median 27 vs 23 days, p=0.021) as was time to ANC recovery (median 38 vs. 29 days, p=0.020). No additional significant differences in individual safety outcomes were observed. Of note, there was no difference in differentiation syndrome that required dose changes or holds between the two cohorts. There were no detectable differences in treatment effectiveness, with 92.7% of patients in the APML4 arm and 93.8% of patients in the ATRA+ATO/GO arm achieving a CR at end of induction (Table 2). With a median follow-up of 35 months, neither group reached the median for overall survival and the estimated 36-month survival was similar between cohorts; 92.5% (95%CI 84.3-100) for APML4 and 94.1% (95%CI 83.1-100) for ATRA+ATO+GO. Conclusion ATRA+ATO-based regimens yield similar short- and long-term efficacy in a high-risk APL population, though hematologic recovery occurred earlier in the ATRA+ATO+GO cohort. No clinically significant differences in acute toxicities exist between APML4 and ATRA+ATO+GO induction strategies as demonstrated by this real-world multicenter analysis.

Results of a Second, Prespecified Analysis of the Phase 2 Study ELM-2 Confirm High Rates of Durable Complete Response with Odronextamab in Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) with Extended Follow-up

Background The class of CD20×CD3 bispecific antibodies (BsAbs) has emerged as an important anti-lymphoma modality for patients (pts) with R/R B-cell non-Hodgkin lymphoma. Odronextamab, a novel, off-the-shelf, CD20×CD3 BsAb, has previously demonstrated compelling efficacy in both R/R diffuse large B-cell lymphoma and R/R FL. In pts with R/R FL, odronextamab monotherapy achieved 75% complete response (CR) rates and encouraging durability of responses, and showed generally manageable safety, in the Phase 2 ELM-2 study (NCT03888105; Kim TM, et al. ASH. 2022). Here, we report the results of a second, pre-specified interim analysis of ELM-2. Methods Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1-4. Optimization of the step-up regimen to further mitigate cytokine release syndrome (CRS) was reported previously (Kim TM, et al. ASH. 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1, followed by 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance treatment continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Pts who achieved a durable CR for ≥9 months transitioned to dosing every 4 weeks. A pre-specified interim analysis was performed when 80 pts had completed ≥12 months follow-up. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included CR rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and changes in scores of patient-reported outcomes. Minimal residual disease (MRD) was included as an exploratory endpoint. Results At data cut off (Jan 31, 2023), the global study was fully enrolled and included 140 safety-evaluable pts with FL; 128 pts were efficacy-evaluable and 85 pts had ≥12 months follow-up. The median duration of study follow-up for efficacy was 26.6 months. In the safety-evaluable FL population, median age was 60.5 years (range 22-84), 53% were male, and pts had received a median of 3 (range 2-13) prior lines of therapy. 73% of pts were refractory to their last therapy, 41% were double refractory, and 74% were refractory to an anti-CD20 antibody. 50% of pts had progression of disease within 2 years (POD24) and 29% had a prior autologous hematopoietic stem cell transplant. ORR and CR rate by ICR were 80% (102/128) and 72% (92/128), respectively, and were consistent across pts with high-risk features. Responses were durable, with both median DoR and duration of CR of 21.7 months; the probability of maintaining CR for 24 months was 48%. Median PFS was 20.7 months (95% CI: 16.7-26.5) and median OS was not reached; the probability of survival at 3 years was 63%. Patient-reported overall quality of life (QoL) scores were maintained during the course of treatment. MRD status at 12 weeks was highly predictive of PFS. Safety was generally consistent with previous reports, and no new treatment-related Grade (Gr) 5 events were recorded since the first interim analysis. The most common treatment-emergent AEs (&amp;gt;30% all grades) were CRS (55%), anemia (34%), neutropenia (34%), and pyrexia (33%). With the optimized 0.7/4/20 mg step-up regimen (n=72), 98% of CRS events were Gr 1/2, and only one pt had Gr 3 CRS. All CRS events resolved with supportive measures; 13 pts received tocilizumab for CRS management with the optimized regimen. Only one low-grade ICANS event was reported with the optimized regimen. Gr ≥3 infections occurred in 50 (36%) pts (Gr 5, n=14 [10%]); COVID-19 infections were reported in 46 (35%) pts (Gr 5, n=8 [6%]). Conclusions The results of this pre-specified analysis of the Phase 2 ELM-2 study continue to demonstrate deep and durable responses with odronextamab in heavily pretreated, refractory pts with R/R FL. 90% of responders were complete responders, with a 48% probability of maintaining CR for 2 years. High CR rates appear to translate to favorable, long-term survival outcomes in the setting of incurable disease. The incidence of AEs was consistent with earlier reports, with no new treatment-related Gr 5 events. Importantly, continued treatment with odronextamab had no detrimental effects on overall QoL. These data underscore the promise of odronextamab as a potentially effective agent for the management of R/R FL. Updated data will be presented.

Maintenance of Moderate to High Levels of Functioning and Quality of Life with Odronextamab Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma

Background: Goals of patient-centered care for management of relapsed or refractory follicular lymphoma (R/R FL) are to improve clinical outcomes while maintaining or improving health-related quality of life (HRQoL). In ELM-2 (NCT03888105), a Phase 2, open-label, multicohort, multicenter study, odronextamab monotherapy demonstrated high and durable complete response rates and generally manageable safety in patients with R/R FL. We report here, for the first time, patient-reported outcome (PRO) results from ELM-2 in patients with R/R FL. Methods: Patients with R/R FL Grade 1-3a received odronextamab IV at 80 mg weekly in 21-day cycles in Cycles (C) 1-4. Optimization of the step-up regimen to mitigate cytokine release syndrome (CRS) was reported previously. Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg in C1, then 80 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance continued at 160 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (≥9 months) switched to dosing every 4 weeks. Patients completed EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L questionnaires at Weeks 1 (baseline), 2, 3, 4, and 10, then every 8 weeks for the remainder of the first year and every 12 weeks in the second year. Results here focus on six key PRO scales: EORTC QLQ-C30 Global Health Status/Quality of Life (GHS/QOL), physical functioning (PF), role functioning (RF), and fatigue; FACT-Lym lymphoma subscale (LymS); and EQ-5D-3L visual analog score (VAS). Longitudinal analyses using mixed models for repeated measures (MMRM) were conducted through Week 50 (the last visit with ≥10 patients with PRO data). Changes from baseline were considered statistically significant if the 95% confidence interval did not contain zero. No adjustment for multiplicity was performed, hence all statistical significance is nominal. Published ranges for minimum important difference (MID) to define clinically meaningful changes are: EORTC QLQ-C30 scales, 10 points; FACT-Lym LymS, 2.9-5.4 points; and EQ-5D-3L VAS, 7-12 points. For responder and time to definitive deterioration (TTDD) analyses, the upper end of these published MID ranges was used to define deterioration or improvement. Results: At the ELM-2 interim data cutoff on 31-Jan-2023, 140 patients with R/R FL Grade 1-3a had received at least 1 dose of odronextamab. Median age was 60.5 years (range: 22-84), with 38.6% ≥65 years, 52.9% male, 57.1% White, 32.1% Asian, 52.2% ECOG=0, and 47.1% ECOG=1. Median duration of follow-up was 26.6 months (range: 6.2-37.5). PRO completion rates for EORTC-QLQ-C30, FACT-Lym, and EQ-5D-3L were high at baseline and remained high for all assessments through Week 50. At baseline, moderate levels of general health (GHS/QoL) and high levels of functioning (PF and RF) were observed that were higher (better) than reference values for general cancer or non-Hodgkin's Lymphoma (NHL). Fatigue scores at baseline were lower (less symptoms) than reference values for general cancer or NHL. EORTC QLQ-C30 GHS/QOL, PF, RF, and fatigue scores were maintained from baseline through Week 50 (Table). For EQ-5D-3L VAS, the overall estimated mean changes from baseline improved statistically significantly but did not reach MID thresholds (Table). For FACT-Lym LymS, overall estimated mean change from baseline statistically significantly improved, and scores improved statistically significantly from Weeks 10 to 42 (except Week 34), with clinically meaningful improvements at Weeks 26 and 42 (Figure). The proportion of patients reporting meaningful improvement or stability across the six scales was higher than the proportion reporting meaningful worsening through Week 50 (Table). The median TTDD for EORTC-QLQ-C30 GHS/QoL was 22.41 (95% CI: 14.59 to not yet reached) months, corresponding to the median PFS. Median TTDD was not reached for EORTC QLQ-C30 PF, FACT-Lym LymS, and EQ-5D-3L VAS scales. Conclusions: For patients with R/R FL, patient-reported HRQoL results were favorable during odronextamab treatment until disease progression, with no detriments on patient-reported symptoms, functioning, and overall quality of life. These results complement encouraging clinical efficacy, durability of responses, and tolerability observed in this highly refractory patient population and support the future role of odronextamab in the management of patients with R/R FL.

Odronextamab Demonstrates Durable Complete Responses in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Progressing after CAR-T Therapy: Outcomes from the ELM-1 Study

Background Chimeric antigen receptor (CAR) T-cell therapies have recently been established as an important option for the management of relapsed/refractory (R/R) DLBCL. However, real-world studies suggest that approximately half of all patients (pts) receiving commercial CAR-T therapies will relapse within 6 months. These pts have a poor prognosis, with estimated overall survival (OS) of only 5 months, indicating a significant unmet need. Odronextamab is a novel, off-the-shelf, CD20×CD3 bispecific antibody that has demonstrated activity in both R/R follicular lymphoma and R/R DLBCL. We have previously reported encouraging results with odronextamab from the Phase 1 ELM-1 study (NCT02290951) in pts with R/R DLBCL post CAR-T therapy (Bannerji R, et al. Lancet Haematol. 2022). These results were consistent with the antitumor activity seen in pts with R/R DLBCL from the Phase 2 ELM-2 study (Kim WS, et al. ASH 2022). Here, we present an updated analysis of outcomes in a prespecified cohort of post CAR-T patients from ELM-1. Methods Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1-4. Revisions to the step-up regimen were reported previously (Bannerji R, et al. Lancet Haematol. 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1 to mitigate the risk of cytokine release syndrome (CRS), followed by 160 mg on Days (D) 1, 8, and 15 of C2-4. After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Those pts who achieved a complete response (CR) that was durable for ≥9 months transitioned to dosing with 320 mg every 4 weeks. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included duration of response (DoR), progression-free survival (PFS), and OS. Immune biomarker assessment was an exploratory endpoint. Results As of Dec 20, 2022, 46 pts were treated (safety-evaluable), with 44 pts evaluable for efficacy. For safety-evaluable pts, median age was 63 years (range 27-82), 67% male, 74% Ann Arbor stage III-IV, and 72% were refractory to CAR-T therapy administered in any prior line. 44 pts were evaluable for efficacy after 4.9 months median duration of follow-up. The ORR and CR rate by ICR were 48% (21/44) and 30% (13/44), respectively. Responses were durable, and both median DoR and median duration of CR were not reached. The probability of maintaining a response for 12 months was 62% and the probability of maintaining a CR for 9 months was 86%.A responder analysis of the subgroup of pts who achieved a CR will be presented. The CAR-T treated pts with DLBCL who were evaluable for biomarker analysis (n=10) had lower T-cell counts at baseline compared with CAR-T naive DLBCL pts (n=41 comparable pts who received odronextamab in ELM-2), yet the fold-change of T-cell expansion at C4D15 was greater in CAR-T treated pts versus CAR-T naive pts. T-cell dynamics, such as changes in activation, exhaustion, and memory subsets, will be presented. Safety was generally consistent with that previously reported. Six (13%) pts permanently discontinued odronextamab due to a treatment-emergent AE (device-related infection, pneumonia, dysphagia, gait disturbance, leukemia, and encephalopathy [n=1 each]). The most common treatment-emergent AE was CRS (any grade, 52%). The highest grade of CRS reported was Grade 2, and low-grade CRS events occurred in 46% of pts with the 0.7/4/20 mg step-up regimen. No cases of ICANS were reported in pts with the 0.7/4/20 mg regimen. Grade ≥3 infections occurred in 10 (22%) pts, with no Grade 5 events. No cases of tumor flare were reported. Conclusions Odronextamab monotherapy demonstrates encouraging antitumor activity in heavily pretreated pts who have progressed after CAR-T therapy, with a generally manageable safety profile. Durable CRs were achieved in this difficult-to-treat setting. These data support the potential role of odronextamab in the treatment paradigm for R/R DLBCL. Further studies to evaluate the optimal sequencing and combinations of odronextamab with CAR-T therapy are warranted.

Final Analysis of the Phase 2 ELM-2 Study: Odronextamab in Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background Odronextamab is a novel, off-the-shelf, CD20×CD3 bispecific antibody that has demonstrated consistent anti-lymphoma activity and a generally manageable safety profile in heavily pretreated patients (pts) with both R/R follicular lymphoma and R/R DLBCL. Encouraging results have been reported in pts who have relapsed following chimeric antigen receptor (CAR) T-cell therapy in the Phase 1 ELM-1 study, and in pts with R/R DLBCL in the Phase 2 ELM-2 study (Kim WS, et al. ASH. 2022). Here, we present the final analysis of the R/R DLBCL cohort from ELM-2 (NCT03888105), reporting long-term efficacy and safety outcomes. Methods Intravenous odronextamab was administered weekly in 21-day cycles during Cycles (C) 1-4. Optimization of the step-up regimen to further mitigate cytokine release syndrome (CRS) was reported previously (Kim WS, et al. ASH 2022). Odronextamab was administered with steroid prophylaxis and step-up doses of 0.7/4/20 mg during C1, followed by 160 mg on Days 1, 8, and 15 of C2-4. After C4, odronextamab maintenance treatment continued at 320 mg every 2 weeks until disease progression or unacceptable toxicity. Pts who achieved a complete response (CR) that was durable for ≥9 months transitioned to dosing every 4 weeks. The final analysis was performed when all pts had the opportunity for ≥36 weeks of follow-up. The primary endpoint was objective response rate (ORR), assessed by independent central review (ICR) according to the Lugano classification. Key secondary endpoints included CR rate, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and changes in scores of patient-reported outcomes. Minimal residual disease (MRD) was included as an exploratory endpoint. Results At the time of data cut-off (Jan 31, 2023) the DLBCL cohort was fully enrolled; 141 pts were evaluable for safety and 127 were evaluable for efficacy, with a median duration of follow-up of 26.2 months. In the safety-evaluable DLBCL population, median age was 66 years (range 24-88), 60% male, 80% Ann Arbor stage III-IV, 56% IPI score ≥3, and median prior lines of therapy was 2 (range 2-8). 17% of pts had transformed disease from indolent lymphoma and 5% had Richter's transformation; 12% were double-hit and 6% triple-hit. In total, 57% of pts were primary refractory and 66% were double refractory to an anti-CD20 antibody and an alkylator in any line of therapy. ORR and CR rate confirmed by ICR were 52% (66/127) and 31% (39/127), respectively, and were consistent across high-risk subgroups. Median DoR was 10.2 months (95% CI: 5.0-not estimable [NE]) and median duration of CR was 17.9 months (95% CI: 9.2-NE); the probability of maintaining CR for 24 months was 48%. Patient-reported outcomes were maintained or improved; of special note, patient-reported pain and emotional functioning scores improved from baseline during the course of treatment. MRD status at 12 weeks was highly predictive of PFS. Safety was generally consistent with previous reports. Treatment-related AEs led to odronextamab interruption/delay in 75 (53%) pts and discontinuation in 14 (10%) pts. The most common treatment-emergent AEs (&amp;gt;30% all grades) were CRS (55%), anemia (43%), and pyrexia (42%). With the optimized 0.7/4/20 mg step-up regimen (n=74), 98% of CRS events were Grade (Gr) 1/2, and only one Gr 3 CRS (confounded by pancreatitis) was reported. CRS events resolved with supportive measures; 26% of pts received tocilizumab for CRS management with the optimized regimen. No ICANS events were reported with the optimized step-up regimen. Gr ≥3 infections occurred in 52 (37%) pts (Gr 5, n=16 [11%]); COVID-19 infections were reported in 23 (16%) pts, which were Gr 5 in 6 (4%) pts. Conclusions Results of the final analysis of the ELM-2 study R/R DLBCL pt cohort confirm the highly encouraging clinical activity of odronextamab in a hard-to-treat pt population, including in pts with high-risk features. Responses were deep and durable with a 48% probability of maintaining CR for 2 years. The safety profile was generally consistent with earlier reports and CRS events were predominantly low grade and manageable. Importantly, continued treatment with odronextamab showed no detrimental effects on patient-reported outcomes. Odronextamab may be an important potential option in future management of R/R DLBCL, and these results support the continued investigation of odronextamab in Phase 3 trials. Updated data will be presented.

The Effect of Prophylactic Steroids on Shivering in Adults Undergoing Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Shivering is common following anesthesia and surgery. Corticosteroids (steroids) have been tried to reduce the risk of shivering, but the evidence in favor of their use is uncertain. The primary objective of this review was to evaluate the effect of steroids on the risk of perioperative (intra- and postoperative) shivering versus controls (placebo and active controls). Additional objectives were to assess the risk of severity of shivering, patient satisfaction with shivering prophylaxis, quality of recovery (QoR), and the risk of steroid-related adverse effects. PubMed, Embase, Cochrane Central Registry of Trials, Google Scholar, and preprint servers were searched from inception until November 30, 2022. Randomized controlled trials (RCTs) published in the English language were retrieved, provided they reported on shivering either as a primary or secondary outcome following steroid prophylaxis in adult patients undergoing surgery under spinal or general anesthesia. A total of 3148 patients from 25 RCTs were included in the final analysis. The steroids used in the studies were either dexamethasone or hydrocortisone. Dexamethasone was administered intravenously or intrathecally, while hydrocortisone was administered intravenously. Prophylactic administration of steroids reduced the risk of overall shivering (risk ratio [RR], 0.65 [95% confidence interval {CI}, 0.52-0.82]; P = .0002; I2 = 77%) as well as the risk of moderate to severe shivering (RR, 0.49 [95% CI, 0.34-0.71]; P = .0002; I2 = 61%) in comparison to controls. Administration of intravenous dexamethasone (RR, 0.67 [95% CI, 0.52-0.87]; P = .002; I2 = 78%) and hydrocortisone (RR, 0.51 [95% CI, 0.32-0.80]; P = .003; I2 = 58%) were effective in shivering prophylaxis. For intrathecal dexamethasone (RR, 0.84 [95% CI, 0.34-2.08]; P = .7; I2 = 56%), the null hypothesis of no subgroup difference was not rejected ( P = .47), preventing definitive conclusions about the efficacy of this route of administration. The prediction intervals for both overall shivering risk (0.24-1.70) and risk of severity of shivering (0.23-1.0) precluded generalization of results in future studies. Meta-regression analysis was used to further explore heterogeneity. Factors like the dose and timing of administration of steroids or the type of anesthesia were not found to be significant. Patient satisfaction and QoR were higher in the dexamethasone groups versus placebo. No increased risk of adverse events of steroids was noted versus placebo or controls. Prophylactic steroid administration may be beneficial in reducing the risk of perioperative shivering. However, the quality of evidence in favor of steroids is very low. Further well-designed studies are needed for establishing generalization.