High-dose Systemic Corticosteroids Research Articles

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

Successful Avoidance of Cicatricial Tracheobronchial Stenosis in a Patient With Endobronchial Tuberculosis by Early Administration of Systemic High-Dose Corticosteroids: A Case Report

Successful Avoidance of Cicatricial Tracheobronchial Stenosis in a Patient With Endobronchial Tuberculosis by Early Administration of Systemic High-Dose Corticosteroids: A Case Report

DRESS as a rare differential diagnosis in eosinophilia, skin rash and acute hepatitis

A 21-year-old female patient presented with fever, pharyngitis, lymphadenopathy and generalized exanthema that had started 2 weeks prior. Allergies were not known, the family and travel history were negative. Due to depression, Duloxetine had been taken for 1.5 years, and due to bipolar disorder, a treatment with Lamotrigine was started four weeks prior but was stopped because of increased transaminase levels. Laboratory findings on admission showed eosinophilia (1.327 /nl), lymphocytosis and acute hepatitis (GOT 428 U/l, GPT 438 U/l) with deranged coagulation. Inflammatory parameters were increased. Ultrasound revealed hepatosplenomegaly with ascites. Acute viral or parasitic infection was excluded serologically. A skin biopsy showed a perivascular inflammatory infiltrate, compatible with a drug reaction. An inflammatory infiltrate was found in the liver biopsy, consistent with drug-induced hepatitis. Cough, dyspnea and pleural effusion occurred. In summary of the findings and with the help of the RegiSCAR-Score, the diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) could be made. Under high-dose prednisolone therapy, a gradual decrease of transaminases and reconstitution of liver synthesis could be observed.In patients with eosinophilia, lymphadenopathy, acute hepatitis and generalized exanthema, DRESS is a rare but-due to its potentially life-threatening consequences-important differential diagnosis. The most important measure is to stop the suspected inducing medication immediately. Severe cases should be treated with high-dose systemic corticosteroids.

A Case Report: High Dose Systemic Corticosteroids as the Therapy for Severe Case Impetigo Herpetiformis

A Case Report: High Dose Systemic Corticosteroids as the Therapy for Severe Case Impetigo Herpetiformis

Long-term effects of high-dose systemic corticosteroids on growth and bone mineral density in patients treated for childhood interstitial lung disease (chILD).

Children's interstitial lung disease (chILD) is a rare and potentially life-threatening condition. For many chILD conditions, systemic corticosteroids (sCCS) are considered the primary treatment despite a broad spectrum of potential side effects. We aimed to determine the long-term effects of sCCS treatment on growth, bone mineral density (BMD), and body composition after chILD. This descriptive cross-sectional single-center study included patients diagnosed with chILD before the age of 18 years treated with sCCS in the period 1998-2020. Dual-energy X-ray absorptiometry, anthropometric measurements, bone age determination, and blood tests were performed in 53 (55% males) of 89 eligible patients. Median (range) age was 19.3 (6.4;30.7 years). Participants received a median (range) cumulative sCCS dose of 1144 (135; 6178) mg over a 2.0 (0.1; 13.8) years period and latest dose was administered 11.7 (1.2; 19.6) years before follow-up. Mean delta height (height standard deviation scores[SDS] - target height SDS) was reduced at sCCS treatment initiation (mean: -0.55, 95% confidence interval [CI]: -0.91; -0.20, p < .005) and at sCCS treatment cessation (mean: -0.86, 95%CI:-1.22; -0.51, p < .001), but normalized in the majority at follow-up (mean: -0.29, 95%CI:-0.61; 0.03, p = .07). Mean (SD) BMD z-score for the spine and whole body was -0.34 (1.06) and 0.52 (1.13), with no significant correlation to sCCS dose. Excess body fat (>30% in females, >25% in males) was found in 58% of patients. Long-term treatment with sCCS did not cause significant long-term reduction of height but showed subtle effects on fat mass percentage and BMD. Given the severity of chILD, the observed long-term effects of sCCS on growth and BMD appear acceptable.

IgA nephropathy

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. Anumber of further approaches are currently in clinical trials.

Infectious and Non-Infectious Pulmonary Complications in HCT Patients Treated with Post Transplant Cyclophosphamide (PTCy) Based Gvhd Prophylaxis

Introduction: Pulmonary complications are a leading cause of mortality and morbidity amongst pts undergoing hematopoietic stem cell transplantation (HCT). Increasingly, allogeneic HCT recipients are undergoing HCT with PTCy based GVHD prophylaxis. While lower rates of severe GVHD has been reported with PTCy, increased infection and organ toxicity has also been seen compared with standard calcineurin inhibitor (CNI) prophylaxis. The incidence and outcomes of pulmonary complications, both infectious and non-infectious/immune in pts receiving PTCy remain poorly characterized. Therefore, we aimed to assess for these in this study. Methods: We performed a retrospective review of pts between 2012-2022 who underwent 1st allogeneic BMT and received PTCy as part of GVHD prophylaxis. We identified pts requiring hospitalization for pulmonary complications. Infectious cases were categorized as bacterial, fungal, viral, or mixed. Bacterial pneumonia was defined as fever, cough, dyspnea, purulence sputum, and new or progressive radiographic evidence of infiltrate not explained by a non-infectious cause, treated with at least 5 days of antibiotics. Viral and fungal pneumonia were diagnosed based on identified organism. Noninfectious complications included idiopathic pulmonary syndrome (IPS), diffuse alveolar hemorrhage (DAH), cryptogenic organizing pneumonia (COP), and bronchiolitis obliterans syndrome (BOS). IPS was defined as radiographic evidence of alveolar infiltrates, dyspnea, cough, increased work of breathing or oxygen requirements, exclusion of infection or alternate pathology, and treated with high-dose systemic corticosteroids. DAH was defined as radiographic evidence of widespread alveolar injury, increased work of breathing or oxygen requirements, and persistent and progressive bloody return on BAL. COP was defined as pathologic evidence of organizing pneumonia on transbronchial lung biopsy in the absence of pathogens. BOS was defined as FEV1/FVC &amp;lt;0.7 and FEV1 &amp;lt;75% with a ≥10% decline over &amp;lt;2 years. Results: A total of 224 pts were identified. Median age at HCT was 55 years (20-78) (Table 1). 138 (64%) were male. The median comorbidity index (HCT-CI) score was 3 and median Karnofsky Performance Score was 80. 56%(n=125) pts underwent HCT with nonmyoablative conditioning, 78% (n=157) underwent HCT with a haploidentical donor, and 65% (n=145) of grafts were peripheral blood. 4%(n=10) were current smokers at time of HCT, 38% (n=84) were former smokers. 16% (n=35) had an existing diagnosis of asthma or COPD. 72 (32%) pts were hospitalized for pneumonia at any point after HCT. There were 23 bacterial pneumonias (30%), 20 viral (27%), 13 fungal (18%), and 12 were mixed (17%) (Table 2). There were 4 pts (6%)with documented pneumonia of unknown etiology due to rapid progression to death or hospice. 10 pts (4%) developed IPS with a median onset of 153 days (20-354). 2 pts (1%) developed COP with a mean onset of 754 days (388 - 1119). 5 pts (2%) developed BOS with a median onset of 336 days (153-677). 8 pts (4%) developed DAH with a median onset of 48 days (20-152). Among all patients, 57 pts (25%) required mechanical ventilation at any point post-HCT, and 18 pts (8%) were prescribed home oxygen at any point post-HCT. Overall, 80pts (77%) died due to non-relapse causes. 29 deaths (28%) were pulmonary related, (21 (20%) infectious and 8 (8%) noninfectious). Of the noninfectious pulmonary deaths, 3 pts died due to IPS, and 5 died due to DAH. Conclusion: In our cohort of pts receiving PTCy based GVHD prophylaxis, significant infectious pulmonary complications were common and were fatal in 9.4% of pts. Infections were the major driver of pulmonary related mortality, however, we observed noninfectious/immunologic pulmonary complications at a rate within or only slightly below the previously reported ranges among transplanted pts predominantly receiving CNI based prophylaxis.

Safety, Tolerability, and Pharmacokinetics of Nirsevimab for the Prevention of RSV Disease in Immunocompromised Children Aged ≤24 Months: Music, an Open Label, Phase 2 Trial

Background Immunocompromised children are at increased risk for severe respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs), which can lead to poor outcomes, including death. Nirsevimab, an extended half-life monoclonal antibody that targets the RSV prefusion F protein, is approved in Canada, the EU, Great Britain, and the US for the prevention of RSV lower respiratory tract disease in neonates and infants during their first RSV season. In Canada and the US, approval extends to the second season for children remaining at higher risk for severe RSV disease. Here, we present the full analysis of the MUSIC trial (NCT04484935), a 12-month, Phase 2, open-label, uncontrolled, single-dose study of nirsevimab, designed to evaluate the safety, pharmacokinetics (PK), and emergence of antidrug antibodies (ADA) in immunocompromised children ≤24 months of age. Methods Children aged ≤24 months with ≥1 immunocompromising condition received a single intramuscular injection of nirsevimab 50 mg (if weight &amp;lt;5 kg) or 100 mg (if weight ≥5 kg) prior to their first RSV season or 200 mg if entering their second RSV season (Table 1). Safety, ADA, and PK were evaluated to Day 361 (final database lock April 18, 2023). Adverse events of special interest (AESIs) included immediate hypersensitivity (including anaphylaxis), immune complex disease, or thrombocytopenia. Results One hundred children (first RSV season n=46, second RSV season n=54) were enrolled from 8 countries (Table 1). Immunocompromising conditions included primary immunodeficiency (n=33), systemic high-dose corticosteroid therapy, (n=29), immunosuppressive chemotherapy, (n=20), history of organ or bone marrow transplantation (n=16), other immunosuppressive therapy (n=15), and human immunodeficiency virus infection (n=8; children may have had more than one condition). Six children experienced 8 treatment-related adverse events (AEs; pyrexia n=4, abdominal pain n=1, erythema n=1, rash n=2); all were Grade 1 severity , except 1 event of Grade 2 pyrexia, and occurred within 7 days of dosing. No treatment-related serious AEs or new onset chronic diseases were observed. Six AESIs were reported in 5 children; all were Grade 1 hypersensitivity events limited to cutaneous findings (food allergy n=2, contrast media allergy n=1, urticaria n=2, erythema n=1), with 1 considered treatment-related (erythema). Three deaths occurred (LRTI, septic shock, and suspected tumor hemorrhage); all were determined to be unrelated to treatment. Eleven children developed treatment-emergent ADAs (median titer 200.0; Day 31 n=1, Day 151 n=1, and Day 361 n=9); none experienced a treatment-related serious AE, AESI, or skin hypersensitivity reaction. Of the children who were ADA-positive on Day 361, 1 experienced a treatment-related AE (Grade 1 pyrexia within 60 minutes of dosing), and 1 experienced a Grade 1 rash on Day 104, determined to be unrelated to treatment. Children who were ADA-positive on Day 361 were more likely to have nirsevimab levels below the limit of detection versus ADA-negative children, suggesting an influence of ADA on PK between Days 151 and 361. Nirsevimab serum exposures at Day 151 were similar to levels demonstrated to be effective in preventing medically attended RSV LRTI in healthy children enrolled in the Phase 3 MELODY trial (Figure 1). Fourteen children demonstrated a rapid decline in serum concentrations through Day 151 compared with the rest of the children; a review of their medical histories revealed evidence for protein-losing conditions, including graft versus host disease, chronic liver disease, and nephrotic syndrome, in 9 of the 14 children. Although none met protocol-defined case criteria for medically attended RSV LRTI, 3 children had an RSV-positive LRTI (central or local test) requiring medical attendance (in an inpatient or outpatient setting; all after Day 151), of whom 1 was hospitalized. Conclusions In immunocompromised children aged ≤24 months, a single dose of nirsevimab was well tolerated and no safety concerns arose over 361 days. Levels of ADA were low, with minimal effects on PK and no apparent impact on safety outcomes. Nirsevimab serum exposure was consistent with previous studies in healthy children and supportive of efficacy in this population at risk of severe RSV disease. Some children with underlying protein-losing conditions had a rapid decline in nirsevimab serum concentrations.

Efficacy of high dose systemic versus combined (systemic and intratympanic) corticosteroid therapy in idiopathic sudden sensorineural hearing loss: A prospective randomized trial and risk factor analysis

The pathophysiology and the proper treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) are an ongoing subject of debate. Locally or systemic administered corticosteroids are the most accepted drugs of treatment in reference to ISSNHL (idiopathic sudden sensorineural hearing loss), however, no strong evidence nor guidelines regarding their effectiveness yet exists.In our prospective, randomized, controlled trial 78 participants were enrolled. Patients were randomly assigned based on the day of admission to two groups according to treatment: group SS (n = 43) received intravenous systemic methylprednisolone alone, and group CT (n = 35) received intratympanic dexamethasone + systemic methylprednisolone. The primary outcome was to compare the hearing outcomes between the treatment groups based on different, widely accepted categories (Siegel, Kanzaki, modified Siegel and PTA4 gain). In consideration of the secondary outcome, we examined the effect of the various risk factors on the hearing improvement.No differences were detected regarding hearing improvement between the two groups, based on any criteria [Siegel's criteria (p = 0.604); Kanzaki's criteria (p = 0.720); modified Siegel's criteria (p = 0.524) and PTA 4 gain (p = 0.569)]. However, several clinical factors such as vertigo (p = 0.039), or cardiovascular comorbidity (p = 0.02) and the severity of initial hearing loss (p = 0.033) were found to bear a significant impact upon the hearing outcome.To the best of our knowledge, this is the first randomized controlled trial comparing high dose systemic and combination corticosteroid therapy in ISSNHL patients. Our findings suggest coexisting cardiovascular comorbidity, vertigo and severity of the initial hearing loss may bear a significantly higher impact upon hearing improvement, than the additional intratympanic steroid administration.The presented trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (name: Combinated systemic and intratympanic steroid therapy in idiopathic sudden sensorineural hearing loss, No.: 2017–000658-20) and with the ethical approval of The National Institute of Pharmacy and Nutrition (OGYÉI) (protocol No.: 7621, on 2017.02.16.)

IgA nephropathy

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. Anumber of further approaches are currently in clinical trials.

A Case of Bilateral Sequential Sudden Sensorineural Hearing Loss in Protein S Deficiency and Successful Recovery of Hearing After Cochlear Implantation

Bilateral sequential sudden sensorineural hearing loss (SSHL) is a rare and challenging clinical condition, but its association with protein S deficiency has received limited attention. This paper reports a case of bilateral sequential SSHL in a patient with protein S deficiency who underwent cochlear implantation and achieved significant improvement in hearing. The patient received high-dose systemic corticosteroids and anticoagulation therapy before the implantation, which had no significant effect. Cochlear implantation was then performed in the left ear, and the patient showed significant improvement in speech understanding and overall hearing ability. A year later, the patient underwent surgery for the opposite ear with favorable outcome. This case highlights the potential benefits of cochlear implantation in patients with bilateral sequential SSHL and protein S deficiency and emphasizes the importance of considering cochlear implantation as a treatment option in such patients.

Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5mg/day), patients on high-dose SCS (≥ 7.5mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.

5599 Background: Despite recent advances, there remains a significant need for targeted, efficacious treatments for advanced and recurrent endometrial carcinoma (EC). Trop-2 has been demonstrated to be overexpressed in several EC including grade 3 endometrioid adenocarcinoma (96%), and uterine serous carcinoma (65%). Trop-2 overexpression has been found to confer a worse prognosis and predicts disease recurrence. Sacituzumab govitecan-hziy (SG) is an antibody-drug conjugate comprised of a humanized anti-Trop-2 antibody conjugated with the active metabolite of irinotecan, a topoisomerase-I inhibitor. SG is currently FDA-approved for use in metastatic urothelial cancer and metastatic triple-negative breast cancer. Methods: We report results from the stage 1 of an open-label non-randomized phase 2 trial (NCT04251416) established to evaluate the clinical activity of SG in patients with persistent or recurrent EC of epithelial origin with Trop-2 overexpression. Criteria for study participation included radiographically confirmed and measurable persistent or recurrent EC, progression after or during platinum-based chemotherapy, and at least 2+ staining of Trop-2. One target lesion by RECIST v1.1 and adequate bone marrow, renal, and hepatic function were required. Patients were at least two weeks beyond prior treatment, major surgery, or high dose systemic corticosteroid use. Patients were given 10mg/kg of SG administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles. This 3-week cycle was continued without rest until disease progression or unacceptable toxicity. Results: Twenty-one patients were enrolled into stage 1. Ten patients (48%) had uterine serous carcinoma, seven (33%) had endometrioid adenocarcinoma, three (14%) had carcinosarcoma, and one patient had mixed serous and clear cell histology. All patients received at least one prior line of chemotherapy, (median 3 lines, range 1-6). At the time of submission, 20 patients were response-evaluable (Table); seven (35%) achieved objective response (5 out of 7 confirmed). Eighteen patients were evaluable for durable disease control; 7 (39%) achieved it. Follow-up durations had a median (IQR) of 15.6 (5.7–22.5) months. Median OS was 22.5 months, and median PFS was 5.7 months. The treatment was well-tolerated with no new or unexpected safety signals reported. Conclusions: Sacituzumab govitecan shows remarkable clinical activity against some of the most historically challenging and chemotherapy-resistant endometrial pathologies and demonstrates a favorable safety profile. With these promising results, we will begin the stage 2 expansion of this phase 2 trial. Clinical trial information: NCT04251416 . [Table: see text]

A Rare Case of Meningoencephalo-Myelitis with a Tubercular Origin

Tuberculosis (TB) can affect any bodily system including the central nervous system (CNS). CNS involvement in Tb is fairly uncommon with poor prognosis due to its high mortality and morbidity. Though meningoencephalitis is a frequent presentation of TB, myelitis along with it is rare. Due to the lack of detailed information about meningoencephalo-myelitis, the risk factors and prognosis of these patients are not fully understood. We report such a rare instance of tuberculosis involving the brain, meninges and spinal cord. The patient was a 13-year-old female with the complaints of fever, both lower limb weakness and urinary retention. The diagnosis was made based on the patient’s medical history and physical examination which showed meningeal syndrome, spinal cord and cranial nerve involvement. The diagnosis was confirmed by the analysis of cerebrospinal fluid, magnetic resonance imaging of the brain and spinal cord, and biochemical evidence of tuberculous infection. The patient had a marked clinical improvement and complete neurologic recovery after anti-tubercular treatment and high doses of systemic corticosteroids. The purpose of presenting the case is to share the bizarre presentation of CNS tuberculosis, a diagnostic and therapeutic emergency. Early diagnosis and immediate management may help with the unfavorable prognosis and our report hopes to shed light on it. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 225

Role of Thalidomide in the management of complicated Tuberculous Meningitis (S25.005)

<h3>Objective:</h3> The optimal management of TBM complications like opto-chiasmatic arachnoiditis, spinal arachnoiditis, vasculitic infarcts, tuberculomas (esp. paradoxical as well as persisting lesions), and hydrocephalus remains to be defined. These patients are managed by the continuation of ATT and administration of high-dose systemic corticosteroids. Some authors suggest more aggressive immunomodulation. <h3>Background:</h3> To study the role of Thalidomide in managing complications in patients of Tuberculous meningitis (TBM) despite being on the best medical therapy <h3>Design/Methods:</h3> The present study included 59 patients of Opto-chiasmatic arachnoiditis, 33 patients of spinal arachnoiditis with myelitis, and 27 patients with a paradoxical increase in the size of tuberculomas on follow-up despite being on full dose anti-tubercular drugs (ATT) and steroids. Imaging (Baseline MRI and follow-up MRI at 3 months and 1 year of treatment) was done in all patients. <h3>Results:</h3> The mean duration of appearance of vision loss despite being on treatment varied from 4 weeks to 9 months. The patients with spinal arachnoiditis with myelitis showed worsening from 2 weeks to 6 months, and a paradoxical response was observed as late as 8 months in a few patients. All these patients were treated with Thalidomide at the dose of 2–3 mg/ kg body weight (Range of 50–150 mg/ day), which was continued for an average of 6 months duration. Of 59 patients with vision loss, 39 patients showed clinical improvement in visual acuity, while 21 out of 33 patients with spinal arachnoiditis showed clinical improvement, and 18 out of 27 patients showed either reduction or healing of tuberculomas after starting this immunomodulation. Baseline MRI in most patients (&gt;95%) showed abnormalities in the form of arachnoiditis, tuberculomas, etc., which on 2–3-month follow-up Imaging showed worsening of radiological features and responded well after starting Thalidomide. <h3>Conclusions:</h3> Thalidomide is a promising immunomodulator, especially in complicated TBM cases due to worsening arachnoiditis and tuberculomas. <b>Disclosure:</b> Dr. Modi has nothing to disclose. Dr. Shree has nothing to disclose. Dr. Kakkar has nothing to disclose. Manoj Goyal has nothing to disclose. Kusum Sharma has nothing to disclose.

Abstract OT2-10-01: A phase 2, randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer

Abstract Background: Improving outcomes for patients (pts) with triple-negative breast cancer (TNBC) remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) and single-agent sacituzumab govitecan, a trophoblast cell-surface antigen 2–targeted antibody-drug conjugate coupled to SN38 via a proprietary, hydrolysable linker, are approved in newly diagnosed pts with programmed death-ligand 1 (PD-L1)–positive tumors and pts who received ≥2 prior systemic therapies (≥1 for metastatic disease), respectively. However, additional options are urgently needed, particularly for pts with tumors that do not express PD-L1 and for those with progression on chemo ± ICI. Magrolimab is an antibody blocking CD47, a “don’t eat me” signal overexpressed on cancer cells, including TNBC, inducing tumor phagocytosis by macrophages. Magrolimab has shown preclinical activity and promising clinical efficacy in hematologic and solid tumors. Chemo agents, including taxanes, can enhance prophagocytic signals on tumor cells, leading to the potential for synergistic antitumor activity with magrolimab. This study is evaluating the safety/tolerability and efficacy of magrolimab in combination with nab-paclitaxel/paclitaxel or with sacituzumab govitecan in unresectable locally advanced/metastatic TNBC. Trial Design: This open-label, 2-cohort (C) study consists of safety run-in and phase (ph)2 portions evaluating nab-paclitaxel/paclitaxel (choice) + magrolimab (safety run-in) or ± magrolimab (ph2, randomized 1:1) in pts with untreated, advanced/metastatic TNBC ineligible for ICI (C1) and magrolimab + sacituzumab govitecan (safety run-in and ph2) in pts with advanced TNBC who received 1 prior systemic treatment in the metastatic setting (C2). Stratification factors for C1 are neoadjuvant and/or adjuvant taxane therapy, liver metastases, and nab-paclitaxel vs paclitaxel. In both cohorts, magrolimab will be administered intravenously (IV) in de-escalating doses to establish the recommended ph2 dose (RP2D). Nab-paclitaxel/paclitaxel and sacituzumab govitecan will be administered IV per standard of care. Eligibility Criteria: Eligible pts are ≥18 y with PD-L1–negative, untreated, unresectable locally advanced/metastatic TNBC (C1) or unresectable locally advanced/metastatic TNBC who received 1 prior line of therapy in the advanced setting, including a taxane and an ICI if PD-L1 positive (C2), with measurable disease per RECIST v1.1. Exclusion criteria include active central nervous system disease, red blood cell transfusion dependence, or prior treatment with CD47/signal regulatory protein α–targeting agents for both cohorts. Additional exclusions are disease progression within 6 months of (neo)adjuvant therapy or rapid visceral progression and/or symptomatic disease, for which single-agent chemo would not be appropriate (C1); chronic inflammatory bowel disease and a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment, prior treatment with topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor, and receipt of high-dose systemic corticosteroids within 2 weeks of cycle 1 day 1 (C2). Specific Aims: The primary objectives are safety/tolerability and magrolimab RP2D (safety run-in) and efficacy (ph2: C1, progression-free survival [PFS]; C2, objective response rate [ORR]; both by investigator). Secondary objectives include ORR, PFS, and duration of response by investigator and independent central review, overall survival, and magrolimab concentration vs time and antidrug antibodies. Present and Target Accrual: The study is enrolling in the US, Australia, and Hong Kong. Target accrual is 144 pts. Contact Information: ClinicalTrials.gov: NCT04958785. Citation Format: Natalie Rainey, Rohit Joshi, Joanne Win Yang Chiu, Ann Chen, Hao Wang, Jared Odegard, Michael Howland, Sylvia Adams. A phase 2, randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-10-01.

Sympathetic Ophthalmia: Demographic Characteristics, Clinical Findings, and Treatment Results.

To evaluate the demographic characteristics, clinical findings, and treatment approach of patients with sympathetic ophthalmia (SO). The records of 14 patients with SO between 2000 and 2020 were retrospectively reviewed. The patients' Snellen best corrected visual acuity (BCVA), detailed ophthalmological examination, optical coherence tomography (OCT), enhanced depth imaging-OCT (EDI-OCT), fundus fluorescein angiography findings, and treatment approaches were recorded. The study included the 14 sympathizing eyes of 14 patients with SO (7 female, 7 male). The mean age was 48.5±15.4 years (range: 28-75), and the mean follow-up duration was 55.1±48.7 months (range: 6-204). Ten patients (71%) had a history of ocular trauma and 4 (29%) had a history of ocular surgery. The time to symptom onset in the sympathizing eye after trauma or ocular surgery ranged from 15 days to 60 years. The most common posterior segment findings were optic disc edema (36%) and exudative retinal detachment (36%). In the acute period, the mean choroidal thickness value on EDI-OCT was 716.5±63.6 μm (range: 635-772) and decreased to 296±81.6 μm (range: 240-415) after treatment. Treatment with high-dose systemic corticosteroid was given to 8 patients (57%), azathioprine (AZA) to 7 (50%), AZA and cyclosporine-A combination to 7 (50%), and tumor necrosis factor-alpha inhibitors to 3 patients (21%). Recurrence was observed in 4 patients (29%) during follow-up. At last follow-up, BCVA values were better than 20/50 in 11 (79%) of the sympathizing eyes. Remission was achieved in 13 patients (93%), but 1 patient (7%) lost her vision due to acute retinal necrosis. SO is a bilateral inflammatory disease that presents with granulomatous panuveitis after ocular trauma or surgery. Favorable functional and anatomical results can be obtained with early diagnosis and initiation of appropriate treatment.

Poststeroid panniculitis in an 11-month-old boy after rapid cessation of high-dose systemic corticosteroids

Poststeroid panniculitis in an 11-month-old boy after rapid cessation of high-dose systemic corticosteroids

B-cell targeted therapy of pemphigus.

Pemphigus is an autoimmune disease that causes blistering and erosion of the skin and mucous membranes because of autoantibodies against desmoglein, which plays an important role in adhesion between epidermal keratinocytes. Treatment of pemphigus has long been centered on corticosteroids, and the guidelines for management of pemphigus have recommended high-dose systemic corticosteroids as the first-line treatment. While guideline-based treatment has been shown to be beneficial in patients with pemphigus, it has also become clear that this treatment is accompanied by significant burden and risk. The challenge for future pemphigus treatment is to maximize efficacy while minimizing risk during the course of the disease. In this regard, treatment targeting B cells is expected to become increasingly important as autoreactive B cells in pemphigus patients are thought to play a major role in the production of autoantibodies, which form the basis of the pathogenesis. The recent expansion of insurance coverage to rituximab, a monoclonal antibody against CD20, for refractory pemphigus in the USA, Europe, and Japan has opened up a new era of pemphigus treatment by enabling treatment strategies with drugs targeting B cells in patients. Here, we discuss the current status and future prospects of pemphigus treatment, focusing on rituximab and Bruton's tyrosine kinase inhibitors, which are expected to become essential drugs for pemphigus treatment in the future.

Effective Treatment of Low Risk Acute Gvhd with Itacitinib Monotherapy

Introduction The primary treatment of acute graft-versus-host disease (GVHD), prolonged courses of high dose systemic corticosteroids (SCS), cause significant morbidities, including an increased risk of serious infections. We used validated clinical (Minnesota standard [Minn std] risk) and biomarker (Ann Arbor [AA] 1) criteria to identify a group of patients with GVHD that is low risk (LR) for treatment failure and non-relapse mortality (NRM) and who might benefit from less toxic alternatives to SCS. Itacitinib (ita), a novel JAK1 inhibitor, blocks the inflammatory cytokine pathways key to target organ damage without the myelosuppression of JAK1/2 inhibitors such as ruxolitinib. We tested the hypothesis that ita monotherapy would be a safe and effective primary treatment of low risk GVHD in a multicenter phase II trial and compared outcomes to a matched control cohort of MAGIC pts with LR GVHD treated with SCS. Methods From February 2019 to April 2021, 70 pts with LR GVHD (Minn std risk/AA1) GVHD were treated with ita 200mg/day for 28 days; responders were allowed a second 28 day cycle. Ita was discontinued without tapering. Biomarker scores were available within 30 hours from sample collections, and treatment could be delayed up to 4 days after screening to accommodate a mostly outpatient population. A contemporaneous cohort of 140 control pts, matched for key characteristics, including target organ severity, donor type, HLA-match, and GVHD prophylaxis, was created from the Mount Sinai Acute GVHD International Consortium (MAGIC) database and biorepository. Control pts were treated with standard doses of SCS (median starting dose 1.1 mg/kg). ORR at 28 days of treatment was defined as the proportion of pts achieving complete or partial response of GVHD symptoms without additional systemic therapy. Infections required laboratory/imaging proof and were considered serious if they required systemic treatment. Results Both ita and SCS treatment produced excellent ORR (ita: 89%; SCS: 86%; p=0.67) including in pts with lower GI GVHD (86% vs 86%, p=1). Similarly high ORR was observed for both cohorts for all subgroup comparisons including by GVHD grade, target organ involvement, age, donor type, HLA-match, conditioning regimen, GVHD prophylaxis, and number of days post-BMT to treatment initiation. ORR was unaffected by the time from screening to initiation of ita (≤48 hours: 90%; >48 hours: 87%; p=1). Significantly more patients treated with itacitinib achieved a response by day 7 compared to those treated with SCS (81% vs 66%, p=0.02) and among responders, ORR were equally durable up to day 90 in both groups (89% vs 88%; p=1). There were no significant differences between ita and SCS pts for 1-year relapse (18% vs 21%, p=0.64), chronic GVHD (28% vs 32%, p=0.33), NRM (4% vs 11%, p=0.21), or survival (88% vs 80%, p=0.11). Regarding the safety data of ita monotherapy, the incidence of grade ≥3 non-hematologic and non-infectious TEAEs was similar to the SCS cohort with no event occurring in >10% of pts. The incidence of new or worsening grade ≥3 neutropenia, anemia, or thrombocytopenia was similar between ita and SCS cohorts. In fact, grade ≥3 leukopenia occurred less frequently in the ita group (16% vs 31%, p=0.02). Ita treatment resulted in an 91% lower cumulative steroid dose through day 28 compared to SCS (1.9 vs 22.0 mg/kg, p<0.001) and fewer pts developed at least one serious infection within 90 days (27% vs 42%, p=0.02; Fig 1). The mean number of infections per pt was also lower (0.43 vs 0.66; rate ratio 0.65 [0.43-0.97]), as was the likelihood of developing a severe (BMT CTN grade 2 or 3) infection (odds ratio 0.50 [95% CI: 0.27, 0.93]). The reduction in serious infections was driven by fewer viral infections in the ita group (Fig 2), particularly in the first 28 days and not explained by differences in letermovir use. Conclusion A short course of itacitinib monotherapy produced very high response rates that occurred faster than treatment with SCS, were equally durable and with a similar risk for cGVHD in patients treated for LR GVHD. Importantly, ita treatment resulted in significantly less severe leukopenia and a significantly lower incidence of serious infections than SCS, likely a result of dramatically less exposure to systemic steroids. Ita monotherapy should be further studied as primary treatment for LR GVHD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal