Real-world Case Series Research Articles

Results from a Real-World Case Series of Patients with IgAN Who Received at Least 9 Months of Tarpeyo

Results from a Real-World Case Series of Patients with IgAN Who Received at Least 9 Months of Tarpeyo

Real-world case series of maintenance theta burst stimulation therapy following response to acute theta burst stimulation therapy for difficult-to-treat depression.

Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan. Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry. All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence. This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Clinical evaluation of deep learning-based risk profiling in breast cancer histopathology and comparison to an established multigene assay

PurposeTo evaluate the Stratipath Breast tool for image-based risk profiling and compare it with an established prognostic multigene assay for risk profiling in a real-world case series of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients categorized as intermediate risk based on classic clinicopathological variables and eligible for chemotherapy.MethodsIn a case series comprising 234 invasive ER-positive/HER2-negative tumors, clinicopathological data including Prosigna results and corresponding HE-stained tissue slides were retrieved. The digitized HE slides were analysed by Stratipath Breast.ResultsOur findings showed that the Stratipath Breast analysis identified 49.6% of the clinically intermediate tumors as low risk and 50.4% as high risk. The Prosigna assay classified 32.5%, 47.0% and 20.5% tumors as low, intermediate and high risk, respectively. Among Prosigna intermediate-risk tumors, 47.3% were stratified as Stratipath low risk and 52.7% as high risk. In addition, 89.7% of Stratipath low-risk cases were classified as Prosigna low/intermediate risk. The overall agreement between the two tests for low-risk and high-risk groups (N = 124) was 71.0%, with a Cohen’s kappa of 0.42. For both risk profiling tests, grade and Ki67 differed significantly between risk groups.ConclusionThe results from this clinical evaluation of image-based risk stratification shows a considerable agreement to an established gene expression assay in routine breast pathology.

Safety and efficacy of off-label bulevirtide monotherapy in patients with HDV with decompensated Child-B cirrhosis-A real-world case series.

Chronic hepatitis D is the most debilitating form of viral hepatitis frequently progressing to cirrhosis and subsequent decompensation. However, the HDV entry inhibitor bulevirtide is only approved for antiviral treatment of patients with compensated disease. We aimed for the analysis of real-world data on the off-label use of bulevirtide in the setting of decompensated liver cirrhosis. We conducted a retrospective study in patients with HDV with decompensated liver disease at German, Austrian, and Italian centers. We included 19 patients (47% male, mean age: 51 years) with liver cirrhosis Child-Pugh B. The median MELD score was 12 (range 9-17) at treatment initiation. The median observation period was 41 weeks. Virologic response was achieved in 74% and normal alanine aminotransferase was observed in 74%. The combined response was achieved by 42%. The most relevant adverse events included self-limited alanine aminotransferase flares, an asymptomatic increase in bile acids, and the need for liver transplantation. Despite bile acid increases, adverse events were considered unrelated. Clinical and laboratory improvement from Child-Pugh B to A occurred in 47% (n = 9/19). Improvements in the amount of ascites were observed in 58% of the patients initially presenting with ascites (n = 7/12). This report on off-label bulevirtide treatment in patients with decompensated HDV cirrhosis shows similar virologic and biochemical response rates as observed in compensated liver disease. Significant improvements were observed in surrogates of hepatic function and portal hypertension. However, this improvement was not seen in all patients. Controlled trials are needed to confirm the safety and efficacy of bulevirtide in decompensated HDV cirrhosis.

Effectiveness of Dupilumab for Chronic Prurigo in Chinese Patients: A Real-World Case Series Study.

Treatment of chronic prurigo (CPG) is challenging. As an antagonist of IL-4R, dupilumab has shown effectiveness in treating CPG in several clinical studies. Recently, the US Food and Drug Administration (FDA) approved dupilumab for the treatment of prurigo nodularis (PN). The purpose of this study was to examine the efficacy of dupilumab in Chinese patients with CPG, and to analyze the difference in response between subtypes of CPG. This retrospective study included 18 patients with CPG who were treated with dupilumab for at least 16 weeks from March 2022 to October 2022. Disease severity and patient self-assessment questionnaires were assessed at baseline and each visit, including the peak Pruritus Visual Analogue Scale (PP-VAS), Prurigo Activity and Severity Score (PAS), Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Itchy-specific Quality of Life questionnaire (ItchyQoL). After 2 weeks of dupilumab treatment, pruritus scores were significantly reduced as measured by PP-VAS scores. Prurigo Activity and Severity scores decreased significantly at Week 2, whereas IGA improved significantly at Week 8. The DLQI, HADS, and ItchyQoL scores at Week 16 also showed significant improvement from baseline. Patients in all subtypes showed improvement in pruritus and lesion severity. Dupilumab was effective in improving pruritus and lesions in patients with various subtypes of CPG.

Initial Experiences of Selective RET Inhibitor Selpercatinib in Adults with Metastatic Differentiated Thyroid Carcinoma and Medullary Thyroid Carcinoma: Real-World Case Series in Korea

Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site.

B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab regimen for NMOSD: A real-world case series study.

To explore the B-cell proliferation characteristics and monitoring significance under the modified reduced-dose rituximab (mRTX) regimen for neuromyelitis optica spectrum disorder (NMOSD). NMOSD patients treated with mRTX were recruited, and the percentages of total CD19+ B cells and CD27+ memory B cells were dynamically detected by flow cytometry. The annualized relapse rate (ARR) and expanded disability status scale (EDSS) scores were compared before and after mRTX treatment, and the differences in B-cell values were compared between groups. A total of 34 patients with NMOSD were ultimately enrolled. The EDSS score decreased from 2.5 (1.5, 3.0) to 1.3 (1.0, 2.0), and the ARR decreased from 1.0 (0, 2.0) to 0 (0, 0) (p < 0.001). Relapses occurred in 6 patients, with total CD19+ B-cell percentages of 3.25% (2.7%, 3.7%) and CD27+ memory B-cell percentages of 0.3% (0.2%, 0.3%) at initial relapse. Twenty-eight patients (82.4%) remained relapse-free with 84 doses of mRTX. Before 56 repeated doses, the total CD19+ B cells and CD27+ memory B cells were 4.00% (3.14%, 5.32%) and 0.26% (0.17%, 0.40%), respectively. The mean dosing interval was 9.2 months. Both total CD19+ B cells and CD27+ memory B cells proliferated over time after mRTX use, with significantly faster proliferation rates in the later stages. In 28 relapse-free patients, the mean time to reach 1% for total CD19+ B cells was 210 days, and the mean time to reach 3% was 240 days, with the mean interval from 1% to 3% of 65 days. Twenty-five relapse-free patients had no significant differences in maximum, minimum, and mean B-cell values compared to those of 6 patients with relapse. The high rate of B-cell proliferation under the mRTX regimen indicates that closer dynamic B-cell monitoring is required to guide repeated mRTX dosing. Sustained depletion of total CD19+ B cells targeting < 3% of lymphocytes may be feasible, enabling extended dosing intervals.

Real World Evidence of Wearable Smartbelt for Mitigation of Fall Impact in Older Adult Care.

Structured Abstract Falls with major injuries are a devastating occurrence for an older adult with outcomes inclusive of debility, loss of independence and increased mortality. The incidence of falls with major injuries has increased with the growth of the older adult population, and has further risen as a result of reduced physical mobility in recent years due to the Coronavirus pandemic. The standard of care in the effort to reduce major injuries from falling is provided by the CDC through an evidence-based fall risk screening, assessment and intervention initiative (STEADI: Stopping Elderly Accidents and Death Initiative) and is embedded into primary care models throughout residential and institutional settings nationwide. Though the dissemination of this practice has been successfully implemented, recent studies have shown that major injuries from falls have not been reduced. Emerging technology adapted from other industries offers adjunctive intervention in the older adult population at risk of falls and major fall injuries. Technology in the form of a wearable smartbelt that offers automatic airbag deployment to reduce impact forces to the hip region in serious hip-impacting fall scenarios was assessed in a long-term care facility. Device performance was examined in a real-world case series of residents who were identified as being at high-risk of major fall injuries within a long-term care setting. In a timeframe of almost 2 years, 35 residents wore the smartbelt, and 6 falls with airbag deployment occurred with a concomitant reduction in the overall falls with major injury rate.

Efficacy and Safety of Fostamatinib in Elderly Patients with Immune Thrombocytopenia: A Single-Center, Real-World Case Series

Background: Fostamatinib is an oral small molecule spleen tyrosine kinase (Syk) inhibitor that was approved for treatment of adult patients with immune thrombocytopenia (ITP) in second-line therapy [1]. Syk inhibition prevents cytoskeletal rearrangements during phagocytosis allowing platelet survival in ITP. The efficacy of fostamatinib in adults with chronic ITP has been established in phase 3 clinical trials [2], and further studies have established fostamatinib as an effective second-line treatment [3]. However, fostamatinib treatment in elderly patients with ITP has not been well established. These individuals pose a particular challenge with a higher risk of bleeding [4], having multiple comorbidities, and may be at increased risk of toxicity from treatments such as fostamatinib. Methods: We performed a retrospective review of all elderly patients (age greater than or equal to 65 years) who had started on fostamatinib between June 1, 2021 and May 31, 2022 for the treatment of ITP at a single tertiary care centre to evaluate its efficacy and safety. Results: Seven patients, median age 80 years (range 78 - 94), four women and three men, all Caucasian background, with various comorbidities started fostamatinib 100mg oral twice daily as second or subsequent line therapy. Patients had a diagnosis of ITP for a median 6 years (range approximately 6 months - 30 years), had six comorbidities (range 2 - 14), and experienced 2 unique prior lines of ITP therapy (range 1 to 6). Over 1290 days of fostamatinib exposure, two patients required dose escalation to 150mg oral twice daily while five patients remained on initial starting dose of 100mg twice daily in partial or complete response. The median platelet count at time of initiating fostamatinib was 25 x 109/L (range less than 10 - 193). Median time to response (defined any first platelet count greater than or equal to 30 x 109/L) was 19 days (range 0 - 181 days) with two patients responding rapidly (5 days and 19 days). Two patients required dose escalation, rescue therapy, and these same two patients discontinued fostamatinib after 175 days and 216 days of treatment. Treatment was tolerated in all patients with no thromboembolic events observed. One death was noted and unrelated to treatment. In keeping with the current recommendations, dose reduction was not required in any of the patients despite their advanced age. Conclusions: Fostamatinib was effective and safe for the majority of our very elderly patients with ITP in second and subsequent line therapies over a cumulative 1290 days of exposure.

The Efficacy and Safety of Fostamatinib in Elderly Patients with Immune Thrombocytopenia: A Single-Center, Real-World Case Series.

Fostamatinib is a small molecule spleen tyrosine kinase (Syk) inhibitor that was approved for the treatment of adult patients with immune thrombocytopenia (ITP) in second-line therapy. Syk inhibition prevents cytoskeletal rearrangements during phagocytosis, allowing platelet survival in ITP. However, fostamatinib treatment in elderly patients with ITP has not been well established. We performed a retrospective review of all elderly patients (age greater than or equal to 65 years) who had started on fostamatinib for the treatment of ITP at a single tertiary care centre to evaluate its efficacy and safety. Seven patients, median age 80 years (range 78-94), four women and three men, all of Caucasian background, with various comorbidities, started fostamatinib 100 mg orally twice daily as second or subsequent line therapy. Patients had a diagnosis of ITP for a median of 6 years (range approximately 6 months-30 years), had six comorbidities (range 2-14), and experienced 2 unique prior lines of ITP therapy (range 1 to 6). Over 1290 days of fostamatinib exposure, two patients required dose escalation to 150 mg orally twice daily, while five patients remained on the initial starting dose of 100 mg twice daily. The median platelet count at the time of initiating fostamatinib was 25 × 109/L (range less than 10-193). The median time to response (defined as any first platelet count greater than or equal to 30 × 109/L) was 19 days (range 0-181 days), with two patients responding rapidly (5 days and 19 days). Two patients required dose escalation and rescue therapy, and these same two patients discontinued fostamatinib after 175 days and 216 days of treatment. Treatment was tolerated in all patients with no thromboembolic events observed. One death was noted and unrelated to treatment. Overall, fostamatinib was effective and safe for the majority of these very elderly patients with ITP.

EP08.02-163 Real-World Case Series on Efficacy and Safety of Amivantamab for EGFR-mutant Non-small Cell Lung Cancer

Amivantamab-vmjw is a newly approved bispecific EGFR/MET antibody for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR Exon 20 insertion mutations, after platinum-based chemotherapy. However, the benefit of Amivantamab for other EGFR-mutant NSCLC, as well as the safety of radiation therapy (RT) concurrent with Amivantamab, were less known.

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion

ObjectivesDiffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. Materials and methodsRetrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. ResultsWe included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). ConclusionsIn this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.

Selumetinib for symptomatic, inoperable plexiform neurofibromas in children with neurofibromatosis type 1: A national real-world case series.

Neurofibromatosis type 1-associated plexiform neurofibromas can cause debilitating symptoms and be life threatening. Treatment options are limited, given their tendency to regrow following surgery and their propensity to transform into malignant tumours following radiation. Selumetinib is an oral selective inhibitor of RAS-mitogen-activated protein kinase (MAPK) 1 and 2, which has shown efficacy for tumour shrinkage/stabilisation and symptom improvement. We report a national case series of 19 children treated with selumetinib. All patients experienced symptom improvement or stabilisation with an acceptable toxicity profile, including those patients previously treated with trametinib. This real-world experience confirms previous trials showing significant clinical benefit for this patient population.

P351 Allogenic adipose-derived mesenchymal stem cells (darvadstrocel) in Japanese patients with complex perianal fistulas in Crohn’s disease

Abstract Background Patients with complex Crohn’s perianal fistulas were treated with allogenic mesenchymal stem cells (darvadstrocel) in pivotal studies, and in clinical practice in Europe since, 2018. However, it is unclear whether the same efficacy and safety could be expected across different ethnic groups. Moreover, it is known that perianal complications including perianal fistulas are more frequent in Asian patients with Crohn’s disease (CD). Methods Japanese adult patients with treatment-refractory complex perianal fistulas in CD were enrolled from, 9 sites in a phase, 3, open-label, single-arm, uncontrolled study. Patients could have, 2 internal and, 3 external openings at maximum, and their luminal disease was non-active or mildly active (CDAI ≤220) at baseline. A single dose (24mL, 120 million cells) of darvadstrocel was intralesionally injected, and results after, 24 and, 52 weeks were evaluated. Primary endpoint was combined remission (a remission rate evaluated clinically and by MRI) at Week 24. Results 22 patients (mean age, 36.4 years, 63.6% male, mean duration of CD, 11.3 years) were enrolled. A half (11/22) had, 1 internal opening (IO) and, 2 external openings (EO) followed by, 1IO-1EO/2IO-2EO/2IO-3EO (3 each, 9/22) and, 1IO-3EO (2/22)., 59.1% and, 68.2% achieved combined remission at Week, 24 (primary endpoint) and Week, 52, respectively. Up to Week, 52, 90.9% (20/22) experienced adverse events (AE), and, 81.8% (18/22) were mild or moderate in intensity. Proctalgia (6/22), nasopharyngitis (5/22), and anal fistula (4/22) were most frequently reported. There was no death or AE-related study discontinuation. Conclusion 52 weeks after administrating darvadstrocel in Japanese patients with complex perianal fistulas in CD, fistula closure was confirmed in, 68% (15/22) and partial closure in, 90.0% (20/22). These findings are consistent with the pivotal study ADMIRE-CD, and real-world case-series reported from Europe. Furthermore, no new safety concerns were identified.

The Promise of Small Data for Telemedicine in Chronic Condition Management: A Real-World Case Series

Connected care is defined as the “real-time, electronic communication between a patient and a provider, including telehealth, remote patient monitoring, and secure email communication between clinicians and their patients” (Alliance of Connected Care). Connected care can create a high-value interaction strategy with patients when it makes thoughtful use of commercially available digital health technologies with demonstrated both clinical and economic effectiveness. Karantis360™, is a home sensor technology that enables real-time tracking, data analytics and predictive care for personal (at home) care powered by IBM Watson Health. IndividuALLyticsTM is a telemedicine platform driven by a patent-pending an N-of-1 analytical engine and related digital dashboards that provides individual, patient-level evaluation of treatment response. The underlying technology combines disparate digital health technology data with the best evidence-base guidelines with N-of-1 methodology. The output allows for creation of personalized treatments empirically tested at the patient-level over time (aka over the course of care). When aggregated both within and across persons, the time-ordered data can build predictive pathways of behavior and ensure the relevant care and medical treatments are in place to support effective medical and self-management of chronic illness. This case-series report describes the implementation of a joint home sensor technology (big data) and an N-of-1 analytic engine (small data) with three elderly consented volunteer customers-patients of Karantis360™. Each person underwent successive, 2-week behavioral change treatment phases to determine usability, utility regarding medical and self-management and any proximal effects on health risks.

Use of dalbavancin in infective endocarditis: a case series.

BackgroundInfective endocarditis, typically caused by Gram-positive organisms such as viridans group streptococci and Staphylococcus aureus, is associated with high mortality and morbidity and requires aggressive, prolonged antimicrobial treatment and sometimes surgery. Dalbavancin, a lipoglycopeptide active against Gram-positive pathogens, has a long half-life, which allows IV treatment as one dose or two doses with a prolonged interval, offering personalized treatment for complex psychosocial situations or facilitating early discharge. In the absence of randomized controlled trials in infective endocarditis, current evidence derives from real-world case series involving off-licence use. The Austrian Society for Infectious Disease and Tropical Medicine includes dalbavancin as an option for infective endocarditis.ObjectivesThis retrospective case series reports use of dalbavancin in a small cohort of patients with infective endocarditis treated at Lancashire Cardiac Centre, Blackpool Teaching Hospitals Foundation Trust, UK.ResultsThe pharmacy database included 11 patients in whom dalbavancin was used to address either complex psychosocial circumstances or the need for early discharge. The endocarditis multidisciplinary team selected dalbavancin from available treatment options. Structures affected by infective endocarditis included aortic, mitral and tricuspid valves; aortic composite grafts; implantable cardioverter defibrillator leads; and prosthetic aortic valves. Eight patients underwent surgery; three were managed conservatively with antibiotics. Dalbavancin was curative in all but one patient, whose signs and symptoms of infection improved. No patients developed adverse reactions.ConclusionsDalbavancin is an alternative treatment option at hospital discharge when conventional antibiotics may not be suitable due to complex psychosocial issues or early discharge is required.

Transitioning From Thrombopoietin Agonists to the Novel SYK Inhibitor Fostamatinib: A Multicenter, Real-World Case Series.

Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor used for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Clinical and operational barriers may exist that warrant bridging or switching from thrombopoietin receptor agonists (TPO-RAs), such as volatility or unpredictability of platelets, adverse events, and quality of life or patient preference. While fostamatinib demonstrated durable platelet responses, the safety and efficacy in combination, bridging, and/or switching with TPO-RAs is not well documented. The objective of this article is to provide guidance from real-world case studies for a safe and effective strategy for the transitioning of patients from TPO-RAs to fostamatinib, with some degree of overlap between the two agents. Currently, the evidence does not exist to guide the safe and effective use of combination therapy or transition between therapies in ITP. This case series highlights the importance to further understand the complexities of managing this disease, as well as successfully combining, bridging, and/or switching patients over to fostamatinib without the need for rescue therapy or increase in adverse events. The need for real-world evidence that guides providers on the safety and efficacy of short- and long-term combination therapy of fostamatinib and TPO-RAs is crucial. The rationale for combination therapy is to target different pathways, platelet destruction, and production without added toxicities. Additionally, gradual tapering off of TPO-RAs may provide a more favorable clinical outcome when switching to fostamatinib. The need for additional data is necessary to provide clinicians with guidance when managing patients with ITP.

Abstract No. 11 Single-center real-world experience of the novel 355 nm Auryon atherectomy device

Peripheral artery disease (PAD) affects more than 200 million adults in the world and is frequently associated with intermittent claudication. Open surgical approaches have been used in the past, but endovascular approaches have evolved as the first line of treatment. The present study details a single-center real-world case series assessing the safety and efficacy of the Auryon atherectomy system in patients with infrainguinal PAD.

Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.

414 Background: There are a lack of published real-world data on treatment patterns for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinical characteristics and treatments among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy. Methods: We performed a retrospective chart review at 26 geographically diverse clinical sites in the US. Patients aged ≥18 years with histologically or cytologically confirmed urothelial carcinoma and radiographic evidence of metastatic or locally advanced disease were identified. Included patients had initiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L setting for la/mUC between May 15, 2016-July 31, 2018. All patients had follow-up through October 31, 2019. Data were summarized using descriptive statistics. Results: Among the 300 patients included in the chart review, 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age at la/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male (66.0%) and White (74.7%). Consistent with age, most patients (82.7%) had comorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation of therapy, a higher proportion of patients who received 1L PD-1/L1i therapy had an Eastern Cooperative Oncology Group performance status of 2 or more than patients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively). Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall, switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapy occurred in approximately 20% of patients, with “better efficacy/survival” noted by treatment teams as the most common reason for switching therapy among this subgroup. Conclusions: In this real-world case series, only a minority of patients with la/mUC who discontinued PD-1/L1i therapy received subsequent therapy. Among those that did, no clear standard of care was observed and approximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.

Food protein-induced enterocolitis syndrome to nuts: An increasing phenomenon

Food protein-induced enterocolitis syndrome (FPIES) is a non–immunoglobulin E (IgE)-mediated food allergy which typically presents in infancy. Although rice is a rare cause of IgE-mediated food allergy, it is one of the most common triggers of FPIES in Australia and the United States. 1 Mehr S. Frith K. Barnes E.H. Campbell D.E. FPIES Study GroupFood protein-induced enterocolitis syndrome in Australia: a population-based study, 2012-2014. J Allergy Clin Immunol. 2017; 140: 1323-1330 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ,2 Ruffner M.A. Ruyman K. Bami S. Cianferoni A. Brown-Whitehorn T. Spergel J.M. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract. 2013; 1: 343-349 Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar Conversely, peanut and tree nuts are rarely described to cause FPIES, but are common triggers of IgE-mediated food reactions. Ruffner et al 2 Ruffner M.A. Ruyman K. Bami S. Cianferoni A. Brown-Whitehorn T. Spergel J.M. Food protein-induced enterocolitis syndrome: insights from review of a large referral population. J Allergy Clin Immunol Pract. 2013; 1: 343-349 Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar reported peanut and tree nut FPIES in only 2% and less than 1% of children, respectively, in a retrospective cohort of 462 children from a single institution. Mehr et al 1 Mehr S. Frith K. Barnes E.H. Campbell D.E. FPIES Study GroupFood protein-induced enterocolitis syndrome in Australia: a population-based study, 2012-2014. J Allergy Clin Immunol. 2017; 140: 1323-1330 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar reported a single case (0.5%) of peanut FPIES in a prospective population-based study of 230 children. Case reports of peanut FPIES have been published, 3 Mansi J. Anvari S. Anagnostou A. Development of peanut allergy despite early introduction: a real-world case series in the United States. Pediatr Allergy Immunol. 2020; 31: 589-592 Crossref PubMed Scopus (2) Google Scholar , 4 Robbins K.A. Ackermann O.R. Carter C.A. Uygungil B. Sprunger A. Sharma H.P. Food protein-induced enterocolitis syndrome to peanut with early introduction: a clinical dilemma. J Allergy Clin Immunol Pract. 2018; 6: 664-666 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar and 1 case of peanut FPIES was noted as a reason for discontinuation in the Learning Early About Peanut (LEAP) allergy trial. 5 Du Toit G. Roberts G. Sayre P.H. et al. Randomised trial of peanut consumption in infants at rick of peanut allergy. N Engl J Med. 2015; 372: 803-813 Crossref PubMed Scopus (1129) Google Scholar We recently noted an increase in the number of children being referred with peanut FPIES to our private allergy services, in Melbourne, Australia.