Prescription Of Immunotherapy Research Articles

A real-life ImmunoCAT study: impact of molecular diagnosis through ImmunoCAPTM ISAC 112 on immunotherapy prescription in pollen-polysensitized patients in Catalonia, Spain.

Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients. To assess the impact of molecular diagnosis through the ImmunoCAPTM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species. A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAPTM ISAC® 112 to recombinant and/or purified allergen components. A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray. Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT.

Why is pet (cat/dog) allergen immunotherapy (AIT) such a controversial topic? Current perspectives and future directions.

Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals".

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen

Background– Cyclophilins are ubiquitous panallergens whose epidemiological, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. The aim of this study was to investigate the epidemiological, diagnostic, and clinical relevance of cyclophilin in seasonal allergic rhinitis and its comorbidities. Methods– We examined a random sample (25%, n 253) of 1263 Italian children affected by seasonal allergic rhinitis from the “Panallergen in Pediatrics” (PAN-PED) cohort. Patients’ disease phenotype had been already fully characterized through questionnaires (ARIA), skin prick tests (ALK), IgE tests to extracts, major and cross-reactive allergenic molecules of a comprehensive variety of allergenic pollen (immunoCAP), and carbohydrate cross-reacting determinants (CCD) (NOVEOS). We also performed nested studies of sensitization prevalence, correlation and allergen extract inhibition in patients (A) sensitized to birch pollen extract but lacking IgE to Bet v 1, Bet v 2, and Bet v 4, (74/1263) or with the highest serum level of IgE to Bet v 1 (26 within 1263), and (B) in patients with sensitization to extracts of ragweed (18), mugwort (18), pellitory (20), Plantago (19), and plane tree (20), but not to their respective major allergenic molecule, profilins and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7 (ImmunoCAP) and extract inhibition tests were performed with the same rBet v 7. ResultsIn the randomized population, IgE to rBet v 7 was detected in 43/253 (17%) patients. It was associated with asthma (p<0.028) and oral allergy syndrome (p<0.017) in univariate, but not in a multivariate analysis adjusted for IgE to profilins (Phl p 12), PR.10s (Bet v 1), and LTPs (Pru p 3). IgE to r Bet v 7 was also highly prevalent (47/74; 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). Conclusions– IgE sensitization to cyclophilin is very frequent in pollen-allergic patients living in temperate areas and can produce “false” positive outcomes in SPT and IgE tests to many different pollen extracts. The spectrum of pollen species containing allergenic cyclophilins is probably broader than previously known. Our results suggest that guidelines of molecular diagnostics should include this allergen family and that new tests based on plant cyclophilins should be produced and used with sera of pollen-allergic patients for a more precise identification of the culprit pollen extract and a tailored prescription of allergen immunotherapy.

Prescription Trends for Hepatocellular Carcinoma Drugs are mirrored by Online Searches

Abstract Background Hepatocellular Carcinoma (HCC) is a major contributor to cancer-related deaths globally. Advancements in immune and molecular therapies have led to more targeted and safer systemic treatments for advanced and unresectable HCC, replacing the use of non-specific chemotherapies. This study aims to provide an overview of online search and prescription activity of drugs used for HCC. Methods Data from IQVIA National Prescription Audit, a comprehensive audit of nearly all monthly US prescription information, was collected from 2017 to 2022 for FDA-approved HCC drugs. Online searches for these drugs were analyzed for visual and quantitative (Spearman's) correlation. Results Online searches for HCC drugs in the US increased 1.17-fold between the first quarter(Q1) 2017 and Q4 2022, while prescriptions increased 5.93-fold during this period. Across first line therapies, lenvatinib was most used with a 27.62-fold increase(Q1 2019-Q4 2022), paralleled by a 1.52-fold increase in online searches. Sorafenib use, however, steeply declined by 17.56-fold(Q1 2019-Q4 2022). For second-line and later treatments, cabozantinib was most frequently applied with 3.04-fold increase and 1.62-fold rise in online searches(Q1 2017-Q4 2022). Immunotherapy prescriptions and online searches for pembrolizumab have surged from Q1 2017-Q4 2022, with an increase of 8.03-fold and 1.37-fold, respectively. Lenvatinib (r = 0.90), cabozantinib (r = 0.67), and pembrolizumab (r = 0.54) had the highest correlations between online searches and prescriptions, and all three showed increasing trends. Oncologists(72.40%) were the largest users of the across specialties in 2022, followed by physician assistants/nurse practitioners(16.53%). Conclusions Over a 5-year period, the utilization of HCC drugs in the US increased and prescription patterns changed due to positive trial results and guideline changes. There was a positive correlation between online searches and prescription trends for HCC drugs. Key messages • High correlation levels between online searches and prescriptions for HCC drugs with increasing usage. • Online search data can mirror prescriptions trends for HCC drugs.

A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy.

e20569 Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.

Real-world rates of FDA-approved targeted therapy and immunotherapy prescriptions for patients with metastatic colorectal cancer in the VA’s National Precision Oncology Program (NPOP).

3602 Background: Colorectal cancer is the fourth most common cancer among Veterans and the third leading cause of cancer-related death in the USA. Use of comprehensive genomic profiling (CGP) to guide administration of FDA-approved biomarker directed therapies can improve outcomes among metastatic CRC (mCRC) patients. We sought to compute the rates of actionable biomarkers and prescriptions of associated FDA-approved therapies among Veterans in NPOP. Methods: The NPOP database was queried to identify mCRC patients who had undergone CGP via tissue or liquid biopsy between February 2019 and July 2022 and had one of the following 5 actionable biomarker profiles: NRAS/ KRAS/ BRAF wildtype, BRAF V600E, MSI-H, TMB-H, or NTRK fusion or rearrangement. The VA’s Corporate Data Warehouse (CDW) was queried to extract prescription data for seven FDA-approved biomarker-directed therapies (targeted agents and immune checkpoint inhibitors (ICIs)). Rates of CGP-directed therapy prescriptions were assessed based upon biomarker and patient characteristics (sex, race, ethnicity, and rurality). Results: A total of 908 mCRC patients underwent CGP, with 81.4% bearing colon adenocarcinoma (COAD) and 18.6% rectal adenocarcinoma (READ). Rates of actionable biomarkers associated with FDA-approved therapies were as follows: NRAS/ KRAS/ BRAF wildtype (34.4%), TMB-H (9.6%), BRAF V600E (7.7%), MSI-H (5.6%), TMB-H and MSI-H (5.6%), and NTRK Fusion or rearrangement (0.3%). The combined rates of any actionable variant were 47.4% for COAD and 44.4% for READ patients. Relative to patients without actionable biomarkers, patients with BRAF V600E mutations were more likely to be older and white; patients with NRAS/ KRAS/ BRAF wildtype were more likely to be younger (all p &lt; 0.001). Among the 424 eligible patients, the frequencies of FDA-approved CGP-directed therapy prescriptions were as follows: MSI-H (70.7%), TMB-H (47.4%), NRAS/ KRAS/ BRAF wildtype (38.5%), and BRAF V600E (17.1%). Across all included biomarkers, African Americans (53.4%) were more likely to receive these therapies than whites (36.8%); and patients with prescriptions were more likely to be younger that those without (all p &lt; 0.01). Conclusions: Nearly 30% of patients with MSI-H mCRC did not receive efficacious ICIs, and though disease laterality data was not readily available, a substantial number of eligible patients also did not receive EGFR inhibitors. This underuse of EGFR inhibitors has been reported previously [1].There were racial and age differences in prescription rates. Further studies should evaluate the barriers to prescribing CGP-directed therapies in the care of mCRC patients. Keywords: molecular testing, metastatic colorectal cancer, comprehensive genomic profiling, actionable biomarkers, FDA approved therapies, veterans. [1] Becker et al. 2021 PMID 34250412.

CHOICE international survey: Clusters of allergen immunotherapy prescription from French and Spanish cohorts

BackgroundThere is no description of the drivers of prescription for allergen immunotherapy (AIT) for respiratory allergic diseases. MethodsA prospective, multicentre, observational, non-interventional real-life study was performed in France and Spain for 20 months. Data were gathered using 2 different questionnaires, anonymously collected in an online platform. No names of AIT products were recorded. Multivariate analysis and unsupervised cluster analysis were performed. ResultsOne hundred and three physicians (50.5% from Spain and 49.5% from France) reported 1735 patients (433 in France and 1302 in Spain), 47.9% males, 64.8% adults with a mean age 26.2 years old. They suffered from allergic rhinitis (99%), allergic conjunctivitis (70.4%), allergic asthma (51.8%), atopic dermatitis (13.9%), and food allergy (9.9%). A clustering analysis based on 13 predefined relevant variables for AIT-prescription identified 5 different clusters, each of them including information regarding doctor's profile and patient demographics, baseline disease characteristics, and main AIT indication: 1) Looking at the future: focusing on asthma prevention (n = 355), 2) Efficacy after discontinuation of AIT (n = 293), 3) Fighting severe allergic disease (n = 322), 4) Looking at the present, facing current symptoms (n = 265) and 5) Doctor's own clinical experience (n = 500). Each one of these clusters have specific patients' and doctors' characteristics, representing distinctive AIT prescription drivers. ConclusionUsing data-driven analysis, we identified for the first time some reasons and patterns of AIT prescriptions in real-life clinical settings. There is no uniform indication for prescribing AIT, which varies amongst patients and doctors with multiple but specific drivers, taking into account several relevant parameters.

INMUNOCAT study: The impact of molecular diagnosis on immunotherapy prescription in pollen polysensitized patients from Catalonia.

Recognition of specific allergens triggering immune response is key for the appropriate prescription of allergen-specific immunotherapy (SIT). This study aimed at evaluating the impact of using the commercially available microarray ImmunoCAPTM ISAC 112 (Thermo Fisher Scientific) on the etiological diagnosis and SIT prescription compared to the conventional diagnostic methods in patients with allergic rhinitis/rhinoconjunctivitis and/or asthma. 300 patients with respiratory allergic disease, sensitized to three or more pollen aeroallergens from different species, as assessed by a skin prick test (SPT) and specific IgE assays (sIgE), were included in this multicentric, prospective observational study. SPT and a blood test were performed to all patients. Total serum IgE and sIgE (ImmunoCAPTM) for allergens found positive in the SPT and sIgE allergen components (ImmunoCAPTM ISAC 112) were measured. According to SPT results, the most prevalent pollen sensitizers in our population were Olea europaea followed by grass, Platanus acerifolia and Parietaria judaica. The molecular diagnosis (MD) revealed Ole e 1 as the most prevalent pollen sensitizer, followed by Cup a 1, Phl p 1, Cyn d 1, Par j 2, Pla a 1, 2, and 3 and Phl p 5. Immunotherapy prescription changed, due to MD testing, in 51% of the cases, with an increase of prescription of SIT from 39% to 65%. The identification of the allergen eliciting the respiratory disease is essential for a correct immunotherapy prescription. The advances in allergen characterization using methods, such as the commercial microarray ImmunoCAPTM ISAC 112, can help clinicians to improve SIT prescription.

Racial and Ethnic Disparities in Allergen Immunotherapy Prescription for Allergic Rhinitis

Racial and ethnic differences exist in the severity of various atopic diseases including allergic rhinitis (AR). Patients of under-represented races and ethnicities may be subjected to disparate subcutaneous allergen immunotherapy (SCIT) prescription practices. To explore the racial and ethnic disparities in the use of SCIT among patients with AR. In this retrospective matched cohort study, we used the TriNetX US Collaborative Network, a multicenter electronic health record-based database to identify patients with AR 18 years and older. Patients were grouped according to their racial and ethnic identification. Study groups were matched for baseline demographics, atopic comorbidities, heart diseases and utilization of β-blockers, and angiotensin-converting enzyme inhibitors. The proportion of patients of under-represented racial and ethnic groups started on SCIT was contrasted to the non-Hispanic White cohort. We identified 1,038,000 patients with AR; the mean age (±standard deviation) at the index was 49.7 (±16.1) years, and 64.6% were female. Ethnicity information was available from 87.3% of patients, and the majority (92.3%) were non-Hispanic. Over a 3-year observation period, fewer Black patients (relative risk [RR], 0.40; 95% confidence interval [CI], 0.33-0.48) and Hispanic patients (RR, 0.80; 95% CI, 0.64-0.99) were started on SCIT compared with non-Hispanic White patients. The proportions of Asian patients who were initiated on SCIT tended to be lower when compared with non-Hispanic White patients (RR, 0.69; 95% CI, 0.47-1.009). In the United States, differences in SCIT prescription exist between Black and Hispanic patients relative to White patients. Barriers to treatment should be explored and mitigated.

Time Trends in Treatment Strategies and Survival of Older versus Younger Patients with Synchronous Metastasised Melanoma-A Population-Based Study in the Netherlands Cancer Registry.

Simple SummaryImmunotherapy has strongly improved outcomes of patients with metastatic melanoma in recent years, but previous studies have shown that survival of older patients often lacks behind. In this study, we investigated treatment prescription of immunotherapy over time in relation to age and survival. We showed that overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group.Around 45% of patients with melanoma are older than 65 years. In recent years, immunotherapy has proven very effective for metastasised melanoma. The aim of this study was to investigate the time trends in treatment strategies and survival in older versus younger patients with synchronous metastasised melanoma. We included all patients diagnosed between 2000 and 2019 from the Netherlands cancer registry. We analysed changes in first-line systemic treatment using multivariable logistic regression models, stratified by age (<65, 65–75, and ≥75). Changes in overall survival were studied using multivariable Cox regression analysis. A total of 2967 patients were included. Immunotherapy prescription increased significantly over time for all age groups (<65 years: 11.8% to 64.9%, p < 0.001; 65–75 years: 0% to 68.6%, p < 0.001; >75 years: 0% to 39.5%, p < 0.001). In multivariable analyses, overall survival improved for patients aged <65 and 65–75 (HR 0.96, 95% CI 0.92–1.00 and HR 0.95, 95% CI 0.89–1.00, respectively), but not in patients over 75 (HR 0.98, 95% CI 0.91–1.05). In conclusion, overall survival has improved in patients with synchronous metastasised melanoma aged <75 years, but not in patients aged 75 years or older. This might be explained by lower prescription rates of immunotherapy in this age group.

Prescription de l’immunothérapie chez les patients « long-répondeurs »

Concerns about the proper schedule for discontinuing immunotherapy have been raised by many clinicians, as well as the minimal check-up required to assess residual disease before stopping immunotherapy. In fact, there currently exist no recommendations concerning immunotherapy prescription and optimal assessment in the event of persistent oncological response in cases of metastatic non-small cell lung cancer (NSCLC). We conducted an online survey among board-certified French Thoracic Oncologists belonging to two professional associations. The survey included multiple-choice questions that either stood alone or were included in case reports. The survey was sent to 490 physicians, of whom 88 responded. For minimal residual disease assessment after 2 years of immunotherapy, PET-scan is prescribed by 92% of respondents and cerebral MRI by 59%. In the event of complete response after 2 years of treatment, 83% of physicians stop prescribing pembrolizumab and 70% discontinue nivolumab. In the event of partial response, 88% of respondents continue immunotherapy. In this case, only 33% use a complementary locoregional treatment such as radiotherapy. Our survey highlights a pronounced tendency to stop immunotherapy in the event of complete oncological response. In the event of partial morphologic response, on the other hand, there is a tendency to continue immunotherapy. However, the use of locoregional treatments remains more heterogeneous.

Atopic Dermatitis and Frequency of Der p 11 Binding as a Major Allergen Revisited

Type 2 inflammation plays a central role in the pathogenesis of atopic dermatitis (AD) encompassing a specific CD4+ T helper type (Th) 2 cell response and the activation of other T-cell lineages, such as Th1, Th17/IL-23, and Th22 (Bakker et al., 2021). House dust mites (HDMs) allergens are likely the most relevant airborne allergen for AD in sensitized and genetically predisposed individuals worldwide (Calderón et al., 2015; Thomas, 2010). Accurate knowledge of the HDM allergens in the patient's environment turns out mandatory in the diagnosis and prescription of effective allergen immunotherapy (Bumbacea et al., 2020; González-Pérez and Poza-Guedes, 2021; González-Pérez et al., 2021).

Allergic patients during the COVID-19 pandemic-Clinical practical considerations: An European Academy of Allergy and Clinical Immunology survey.

BackgroundThe COVID‐19 pandemic has affected health care systems unexpectedly. However, data focusing on practical considerations experienced by health care professionals (HCPs) providing care to allergic patients is scarce.MethodsUnder the framework of the European Academy of Allergy and Clinical Immunology (EAACI), a panel of experts in the field of immunotherapy developed a 42‐question online survey, to evaluate real‐life consequences of the COVID‐19 pandemic in allergy practice.ResultsThe respondents in the survey were 618. About 80% of HCPs indicated being significantly affected in their allergy practice. A face‐to‐face visit reduction was reported by 93% of HCPs and about a quarter completely interrupted diagnostic challenges. Patients with severe uncontrolled asthma (59%) and anaphylaxis (47%) were prioritized for in‐person care. About 81% maintained an unaltered prescription of inhaled corticosteroids (ICS) in asthmatics. About 90% did not modify intranasal corticosteroids (INCS) in patients with allergic rhinitis. Nearly half of respondents kept biological prescriptions unmodified for asthma. About 50% of respondents kept their allergen immunotherapy (AIT) prescription patterns unchanged for respiratory allergies; 60% for insect venom allergies. Oral immunotherapy (OIT) for food allergies was initiated by 27%. About 20% kept carrying out up‐dosing without modifications and 14% changed to more prolonged intervals. Telemedicine practice was increased.ConclusionsHCPs providing care to allergic patients were affected during the pandemic in diagnostic, management, and therapeutic approaches, including AIT for respiratory, insect‐venom, and food allergies. Most HCPs maintained controller treatments for both asthma, and allergic rhinitis consistent with international recommendations, as well as biological agents in asthma. Remote tools are valuable in delivering allergy care.

Experimental and Meta-Analytic Validation of RNA Sequencing Signatures for Predicting Status of Microsatellite Instability.

Microsatellite instability (MSI) is an important diagnostic and prognostic cancer biomarker. In colorectal, cervical, ovarian, and gastric cancers, it can guide the prescription of chemotherapy and immunotherapy. In laboratory diagnostics of susceptible tumors, MSI is routinely detected by the size of marker polymerase chain reaction products encompassing frequent microsatellite expansion regions. Alternatively, MSI status is screened indirectly by immunohistochemical interrogation of microsatellite binding proteins. RNA sequencing (RNAseq) profiling is an emerging source of data for a wide spectrum of cancer biomarkers. Recently, three RNAseq-based gene signatures were deduced for establishing MSI status in tumor samples. They had 25, 15, and 14 gene products with only one common gene. However, they were developed and tested on the incomplete literature of The Cancer Genome Atlas (TCGA) sampling and never validated experimentally on independent RNAseq samples. In this study, we, for the first time, systematically validated these three RNAseq MSI signatures on the literature colorectal cancer (CRC) (n = 619), endometrial carcinoma (n = 533), gastric cancer (n = 380), uterine carcinosarcoma (n = 55), and esophageal cancer (n = 83) samples and on the set of experimental CRC RNAseq samples (n = 23) for tumors with known MSI status. We found that all three signatures performed well with area under the curve (AUC) ranges of 0.94–1 for the experimental CRCs and 0.94–1 for the TCGA CRC, esophageal cancer, and uterine carcinosarcoma samples. However, for the TCGA endometrial carcinoma and gastric cancer samples, only two signatures were effective with AUC 0.91–0.97, whereas the third signature showed a significantly lower AUC of 0.69–0.88. Software for calculating these MSI signatures using RNAseq data is included.

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.

Combining Discordant Serum IgE and Skin Testing Improves Diagnostic and Therapeutic Accuracy for Hymenoptera Venom Hypersensitivity Immunotherapy

Diagnosis of patients with hymenoptera venom hypersensitivity consists of elucidating clinical symptoms suggestive of systemic reaction (SR) and then confirmation of sensitization via intradermal skin testing (IDST) first and serum IgE assays such as ImmunoCAP (ICAP) as a complementary modality of diagnosis. Determine the concordance between ICAP and IDST in patients with a clinical history suggestive of hymenoptera venom SR. Determine whether venom immunotherapy would change on the basis of IDST versus ICAP results. A prospective diagnostic study was designed to test the concordance between IDST and ICAP venom testing in the diagnosis of hymenoptera venom hypersensitivity. This study entailed testing both IDST and ICAP for 5 hymenoptera venoms (honey bee, wasp, yellow jacket, yellow hornet, and white-faced hornet) in both a case group with SR to hymenoptera venom (N= 70) and a control group without SR (N= 51). Significant discordance was observed between positive IDST and ICAP results for any of the 5 hymenoptera venoms (McNemar test, P= .001). In the case group, there was significant discordance for wasp (P < .0001), yellow jacket (P= .002), and white-faced hornet (P= .02). More than 47% of the case patients would have different venom immunotherapy prescriptions if ICAP and IDST had been performed during initial diagnosis versus IDST alone. Our study shows significant discordance between IDST and ICAP; however, they are complementary. On the basis of our data, we propose ICAP testing first followed by IDST for ICAP-negative venoms as an alternative and efficient diagnostic strategy.

Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

ObjectivesImmunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and MethodsData on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo- and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%−71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%−40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%−73.4%) and 29.2% (14.7%−43.9%) using the 1% and 50% cutoffs, respectively. ConclusionConsiderable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data.

Prise en charge des mélanomes cutanés à l'Institut Joliot Curie de Dakar

INTRODUCTION : Le but de ce travail est d’étudier les aspects cliniques et thérapeutiques des mélanomes cutanés à l’Institut Joliot Curie de Dakar. PATIENTS ET METHODES : Nous avons réalisé une étude rétrospective, descriptive et critique à l’Institut Joliot Curie de Dakar incluant tous les cas de mélanomes confirmés par l’histologie entre Janvier 2008 et Décembre 2013. RESULTATS : Au cours de la période d'étude, 21 cas ont été pris en charge. La localisation était plantaire dans 76% des cas. Le type acral était retrouvé dans 85,7% des cas. Tous les patients avaient un niveau de Clark supérieur ou égal à IV avec un indice de Breslow supérieur à deux mm. La chirurgie d'exérèse était réalisée chez 14 patients avec curage ganglionnaire inguinale chez 12 patients. La moyenne de suivi était de 16 mois avec une survie globale de 58,7% à six mois et 51% à un an. CONCLUSION : La majorité des patients présentait un mélanome acral et a bénéficié d’un traitement chirurgical, aucune immunothérapie qui à ce jour a révolutionné la prise en charge des mélanomes avancés n’a été administrée.

НАЧАЛЬНЫЙ ОПЫТ ОЦЕНКИ МУТАЦИОННОЙ НАГРУЗКИ ОПУХОЛИ У ДЕТЕЙ С ГЕПАТОЦЕЛЛЮЛЯРНОЙ КАРЦИНОМОЙ

The level of tumor mutation burden (TMB) is a predictive factor of immune checkpoints that determines the potential effectiveness of immune checkpoint inhibitors and indications for their prescription regardless of the type of tumor in adults and children. However, the prevalence of tumors with high TMB in the pediatric population has not been well studied. Objective of the research: to assess the detection frequency of high TMB (&gt;10 mutations per megabase) in pediatric hepatocellular carcinoma (HCC). Materials and methods of research: Next Generation Sequencing, Ion AmpliSeq™ Comprehensive Cancer Panel (409 genes) of tumor DNA samples from 4 children with HCC was performed. The calculation of the mutational load was carried out according to the work of Z.R. Chalmers et al. Results: out of 4 analyzed samples, TMB levels have lower cut-off value than needed for the immunity checkpoint inhibitors for 2 patients to administer: 5,9 mut/MB (primary tumor), 9,2 mut/MB (metastasis), while in 2 other patients the TMB has level above the threshold – 10,9 mut/MB (primary tumor) and 48,5 mut/MB (relapse metastasis), respectively. Conclusion: this paper presents the initial experience of estimation of the TMB level in children with HCC. In our case series report, the level allowing the prescription of immunotherapy (&gt;10 mut/MB) was observed in 2 patients. Further research on a larger cohort of patients is useful to assess the role of mutational burden in disease prediction and effectiveness of immunotherapy.

@IT2020: An innovative algorithm for allergen immunotherapy prescription in seasonal allergic rhinitis.

Allergen immunotherapy (AIT) is the only disease-modifying treatment in patients with seasonal allergic rhinoconjunctivitis (SAR). Its efficacy depends on the precise identification of the triggering allergen. However, diagnostics based on retrospective clinical history and sensitization to whole extracts (SWE) often leads to equivocal results. To assess the usability and impact of a recently established algorithm for a clinical decision support system (@IT2020-CDSS) for SAR and its diagnostic steps [anamnesis, SWE (skin prick test or serum IgE), component resolved diagnosis, CRD, and real-time digital symptom recording, eDiary] on doctor's AIT prescription decisions. After educational training on the @IT2020-CDSS algorithm, 46 doctors (18 allergy specialists, AS, and 28 general practitioners, GP) expressed their hypothetical AIT prescription for 10 clinical index cases. Decisions were recorded repeatedly based on different steps of the algorithm. The usability and perceived impact of the algorithm were evaluated. The combined use of CRD and an eDiary increased the hypothetical AIT prescriptions, both among AS and GP (p<.01). AIT prescription for pollen and Alternaria allergy based on anamnesis and SWE was heterogeneous but converged towards a consensus by integrating CRD and eDiary information. Doctors considered the algorithm useful and recognized its potential in enhancing traditional diagnostics. The implementation of CRD and eDiary in the @IT2020-CDSS algorithm improved consensus on AIT prescription for SAR among AS and GP. The potential usefulness of a CDSS for aetiological diagnosis of SAR and AIT prescription in real-world clinical practice deserves further investigation.