Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study.

AALL1931, a phase 2/3 study conducted in collaboration with the Children's Oncology Group, investigated the efficacy and safety of JZP458 (asparaginase erwinia chrysanthemi [recombinant]-rywn), a recombinant Erwinia asparaginase derived from a novel expression platform, in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma who developed hypersensitivity/silent inactivation to Escherichia coli-derived asparaginases. Each dose of a pegylated E coli-derived asparaginase remaining in patients' treatment plan was substituted by 6 doses of intramuscular (IM) JZP458 on Monday/Wednesday/Friday (MWF). Three regimens were evaluated: cohort 1a, 25 mg/m2 MWF; cohort 1b, 37.5 mg/m2 MWF; and cohort 1c, 25/25/50 mg/m2 MWF. Efficacy was evaluated by the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA ≥0.1 IU/mL) at 72 hours and at 48 hours during the first treatment course. A total of 167 patients were enrolled: cohort 1a (n = 33), cohort 1b (n = 83), and cohort 1c (n = 51). Mean serum asparaginase activity levels (IU/mL) at 72 hours were cohort 1a, 0.16, cohort 1b, 0.33, and cohort 1c, 0.47, and at 48 hours were 0.45, 0.88, and 0.66, respectively. The proportion of patients achieving NSAA ≥0.1 IU/mL at 72 and 48 hours in cohort 1c was 90% (44/49) and 96% (47/49), respectively. Simulated data from a population pharmacokinetic model matched the observed data well. Grade 3/4 treatment-related adverse events occurred in 86 of 167 (51%) patients; those leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased alanine aminotransferase (1%), and hyperammonemia (1%). Results demonstrate that IM JZP458 at 25/25/50 mg/m2 MWF is efficacious and has a safety profile consistent with other asparaginases. This trial was registered at www.clinicaltrials.gov as #NCT04145531.

Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.

Effectiveness of direct delabelling of allergy labels in type A adverse drug reactions to penicillin: a multicentre hospitalwide prospective cohort study.

BACKGROUND: Patient-reported penicillin allergy labels (PALs) are associated with adverse patient outcomes and inappropriate antibiotic prescribing. Removal of PALs via direct oral challenge (DOC) is associated with increased penicillin utilization post removal. OBJECTIVES: To assess the impact of direct delabelling (allergy label removal via medical reconciliation alone) of type A adverse drug reaction (ADR) PALs on inpatient prescribing. METHODS: From January 2019 to December 2022 at two tertiary hospitals in Melbourne, patients aged ≥18 years with type A ADR PALs, as defined by the validated Antibiotic Allergy Assessment Tool, were offered direct delabelling or single-dose DOC. The primary endpoint was antibiotic use pre- and post-assessment (during index admission and 90 days post assessment). The secondary endpoint was the proportion of patients delabelled in the direct delabelling and DOC cohorts in the electronic medical record at 90 days post assessment. RESULTS: Allergy labels (n = 4108) were assessed for 488 participants, with 490 individual type A ADR PAL assessments included. Three hundred and thirty-seven patients were directly delabelled, 69 underwent DOC and 84 were not delabelled. There was increased use of any penicillin following direct delabelling (OR 19.19, 95% CI 2.48-148.36) and DOC (OR 56.98, 95% CI 6.82-476.19) during the index admission, higher in the DOC group compared with direct delabelling (OR 2.97, 95% CI 1.39-6.37). Relabelling at 90 days was low with no statistically significant difference between direct delabelling (5/337; 1.5%) and DOC (0/69; 0%). CONCLUSIONS: Both direct delabelling and DOC of type A ADR PALs increased penicillin usage; however, the impact was greatest with DOC. Most patients remain delabelled at 90 days.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Drug Allergy in Children: Adverse Reactions after Skin Testing.

INTRODUCTION: Skin tests are one of the most widely used diagnostic tools for suspected drug allergies in children. Studies on systemic reactions occurring during skin testing with allergens have mostly been conducted in pediatric and adult patient groups together. However, data on adverse reactions including allergic reactions after drug skin tests in children are scarce. It is aimed to determine the adverse reactions after skin test in children with suspected drug allergy. METHODS: Patients who underwent a drug skin test due to the suspicion of drug allergy between May 2017 and June 2020 were evaluated, retrospectively. Data about adverse reactions seen after skin testing at the testing area in the clinic were analyzed. RESULTS: The study included 1,073 children (585 [54.5%] boys and 488 [45.5%] girls) with a median age of 7.5 years. A total of 12 (1.1%) reactions were detected after skin testing, and 4 (0.4%) of them were allergic reactions. Of the allergic reactions, three were anaphylaxis and one was urticaria. Two of the reactions (1 anaphylaxis and 1 urticaria) were detected after the skin prick test and the remaining 2 were detected after intradermal test. Three of the nonallergic reactions were considered as vasovagal reactions and seven were considered as nonspecific and anxiety-related reactions. CONCLUSION: Although drug skin tests were generally well-tolerated and adverse reactions were rare, severe allergic reactions including anaphylaxis may ensue. Skin tests should be necessarily performed in clinical settings in experienced centers.

Ibuprofen and Other Arylpropionics: The Relevance in Immediate Hypersensitivity Drug Reactions.

BACKGROUND: Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is the most frequent medication to be involved in hypersensitivity drug reactions (HDRs). Other analgesic/anti-inflammatory drugs in the arylpropionic group are also relevant, albeit to a lesser extent. Ibuprofen is widely consumed by people of all ages, both on medical prescription and over the counter; moreover, it is an organic contaminant of surface waters and foods. While numerous drugs cause HDR, ibuprofen's underlying mechanisms are more intricate and involve both specific immunological and non-immunological mediated reactions. SUMMARY: we concentrate on immediate responses, including urticaria with or without angioedema, anaphylaxis, and angioedema, classifying reactions according to whether they are caused by single or multiple NSAIDs and based on the mechanisms at play. Both groups may experience anaphylaxis, defined as an immediate, severe systemic reaction involving at least two organs, though the frequency and severity can vary. Following this classification, more clinical manifestations can be identified. Diagnosis is partly based on a detailed clinical history, including information about ibuprofen and/or other arylpropionic derivatives involved, the interval between drug intake and symptoms onset, clinical manifestations, number of episodes, and the patient's tolerance or response to other medications - mainly non-chemically related NSAID - both before and after reactions to ibuprofen and/or other arylpropionic drugs. A drug provocation test is frequently necessary to make a diagnosis. KEY MESSAGE: Because ibuprofen is the most widely prescribed NSAID, it is reasonable to assume its role as the leading cause of HDR will only become more important.

One-Bag 8-Step Ferric Carboxymaltose Desensitization Protocol for Patients with a History of Hypersensitivity Reactions to Iron Preparations.

INTRODUCTION: Iron deficiency is the most common cause of anemia in both sexes, although it is more common in women. Intravenous (IV) iron replacement is preferred in patients who cannot tolerate oral treatment or when iron stores need to be replenished rapidly. In this study, we wanted to share the ferric carboxymaltose (FCM) desensitization protocol that we self-created and successfully applied. METHODS: This retrospective cross-sectional study included patients with a history of hypersensitivity reactions (HSRs) to IV or oral iron replacement and patients who were planned to receive IV iron replacement but were referred to the allergy clinic because of have risk factors (atopic diseases, history of HSR to other drugs, high serum tryptase levels, etc.) for HSRs. Before desensitization, some of the patients underwent skin tests (skin prick test and intradermal test) with FCM, and the results were recorded. Skin tests were not performed in patients with a history of drug use (antihistamine, systemic steroid, omalizumab, etc.) that affected the results of skin tests. All patients underwent a one-bag 8-step desensitization protocol with 500 mg FCM and were observed for 2 h after desensitization. RESULTS: A total of 15 patients (14 females and 1 male) with a mean age of 41.13 ± 11.18 years were included in the study. When the patients were evaluated in terms of the risk of allergic reactions according to their clinical history, 8 patients had a history of anaphylaxis with iron preparations (FCM, n = 4; ferric hydroxide sucrose, n = 2; iron [II] glycine sulfate, n = 1; and iron [III] hydroxide polymaltose, n = 1), and 7 patients had a history of HSR other than anaphylaxis with iron preparations (urticaria, n = 6 [FCM, n = 2; iron (II) glycine sulfate, n = 2; and iron (III) hydroxide polymaltose, n = 2] and urticaria + angioedema [ferric hydroxide sucrose, n = 1]). Desensitization was successfully completed in all patients. No HSR was observed during or after the procedure in any of the patients. CONCLUSION: IV iron replacement is a very effective method, especially in cases where iron stores need to be replenished more rapidly. In patients with a history of iron HSR or at risk of developing HSR, replacement can be safely performed without an allergic reaction with successful desensitization protocols.

Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

Desensitization using pegaspargase in the era of commercially available Erwinia: A single-institution report on efficacy, cost, and resource utilization.

BACKGROUND: Pegaspargase is a therapeutic enzyme that is utilized in treatment regimens targeting pediatric acute lymphoblastic leukemia. However, many patients experience hypersensitivity reactions, requiring discontinuation of the therapy. Historically, this necessitated switching to an alternative form of the drug, most commonly asparaginase Erwinia chrysanthemi; however, in recent years this was difficult due to drug shortages and eventually commercial discontinuation. We report here our experience performing pegaspargase desensitizations in patients with prior hypersensitivity reactions. PROCEDURE: Patients with a clinical hypersensitivity reaction to pegaspargase were identified. When due for their next dose, patients were admitted to the pediatric intensive care unit, bone marrow transplant unit, or oncology unit, and underwent desensitization utilizing a rigorous premedication and multistep dilution-based protocol. Serum asparaginase activity levels were drawn after desensitization to assess for therapeutic levels of enzyme activity. RESULTS: We identified 11 patients who underwent a total of 33 desensitizations to pegaspargase and calaspargase pegol-mknl. No patients experienced clinically significant hypersensitivity reactions necessitating stopping the infusion, nor administration of rescue medications. All serum asparaginase activity levels collected demonstrated enzyme activity levels above predefined therapeutic thresholds. Cost analysis revealed substantial savings when patients received asparaginase desensitization over the now commercially available asparaginase E. chrysanthemi (recombinant) rywn. CONCLUSIONS: Performing desensitization to pegaspargase in the pediatric acute lymphoblastic leukemia population is feasible, safe, and effective. It is financially advantageous over available alternative approaches, and requires fewer injections and presentations to care.

Infliximab desensitization in patients with inflammatory bowel diseases: a safe therapeutic alternative.

BACKGROUND: Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. METHODS: We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. RESULTS: From 2005 to 2020, 27 patients (Crohn's Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. CONCLUSION: IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics.What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation.What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity.How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

Hypersensitive Reactions During Hemodialysis Treatment: What Do We Need to Know?

Kidney replacement therapies (KRTs) including hemodialysis (HD) are one of the treatment options for most of the patients with end-stage kidney disease. Although HD is vital for these patients, it is not hundred percent physiological, and various adverse events including hypersensitivity reactions may occur. Fortunately, these reactions are rare in total and less when compared to previous decades, but it is still very important for at least two reasons: First, the number of patients receiving kidney replacement treatment is increasing globally; and the cumulative number of these reactions may be substantial. Second, although most of these reactions are mild, some of them may be very severe and even lead to mortality. Thus, it is very important to have basic knowledge and skills to diagnose and treat these reactions. Hypersensitivity reactions can occur at any component of dialysis machinery (access, extracorporeal circuit, medications, etc.). The most important preventive measure is to avoid the allergen. However, even with very specific test, sometimes the allergen cannot be found. In mild conditions, HD can be contained with non-specific treatment (topical creams, antihistaminics, corticosteroids). In more severe conditions, treatment must be stopped immediately, blood should not be returned to patient, drugs must be stopped, and rules of general emergency treatment must be followed.

Pholcodine and allergy to neuromuscular blocking agents: where are we and how did we get here?

Despite the purported link between pholcodine and neuromuscular blocking agent allergy, screening for prior pholcodine use offers no practical benefit to patients, and anaesthetists should continue to use a neuromuscular blocking agent where this is clinically indicated.

Coronavirus Disease 2019 mRNA Vaccination Appears Safe in Pediatric Patients With Hypersensitivity to Polyethylene Glycolated Escherichia coli L-asparaginase.

Polyethylene glycol-asparaginase (PEGAsp) is an established component of acute leukemia therapy. Hypersensitivity reactions to PEGAsp occur in 10% to 15% of patients, with polyethylene glycol suggested as the antigenic culprit. As coronavirus disease 2019 (COVID-19) mRNA vaccines contain polyethylene glycol, the safety of administration of these vaccines to patients with prior PEGAsp hypersensitivity has been questioned. Between December 21, 2020 and March 3, 2022, 66 patients with acute leukemia and PEGAsp allergy received COVID-19 vaccination. No patients (0/66 0%, 95% CI: 0%-5.4%) experienced an allergic reaction to the vaccine. COVID-19 mRNA vaccination appears to be safe in pediatric and young adult patients with acute lymphoblastic leukemia with PEGAsp allergy.

Progestogen hypersensitivity: successful use of progesterone desensitisation and omalizumab to facilitate in vitro fertilisation.

Hypersensitivity to exogenous or endogenous progesterone presents with a variety of clinical, usually cutaneous, manifestations. The condition can occur at any age during the reproductive years, causes debilitating symptoms and can impact the use of exogenous hormones. Management strategies include symptom control or hormonal manipulation via desensitisation. Strategic testing confirms the diagnosis, while targeted intervention can significantly and positively impact quality of life and further childbearing.

Omalizumab for management of hypersensitivity reactions to anticancer drugs.

Hypersensitivity reactions to anticancer drugs include treatment-limiting toxicity. Standard drug desensitisation offers temporary tolerance and hence requires repetition. We used omalizumab, an anti-immunoglobulin E antibody, to overcome immediate and delayed hypersensitivity reactions to various anticancer drugs. Seven of the eight patients in the current study successfully resumed the desired anticancer drug regimen without standard desensitisation. No safety issues from omalizumab were observed.

Improving the performance of machine learning penicillin adverse drug reaction classification with synthetic data and transfer learning.

BACKGROUND: Machine learning may assist with the identification of potentially inappropriate penicillin allergy labels. Strategies to improve the performance of existing models for this task include the use of additional training data, synthetic data and transfer learning. AIMS: The aims of this study were to investigate the use of additional training data and novel machine learning strategies, namely synthetic data and transfer learning, to improve the performance of penicillin adverse drug reaction (ADR) machine learning classification. METHODS: Machine learning natural language processing was applied to free-text penicillin ADR data extracted from a public health system electronic health record (EHR). The models were developed by training on various labelled data sets. ADR entries were split into training and testing data sets and used to develop and test a variety of machine learning models. The effect of training on additional data and synthetic data versus the use of transfer learning was analysed. RESULTS: Following the application of these techniques, the area under the receiver operator curve of best-performing models for the classification of penicillin allergy (vs intolerance) and high-risk allergy (vs low-risk allergy) improved to 0.984 (using the artificial neural network model) and 0.995 (with the transfer learning approach) respectively. CONCLUSIONS: Machine learning models demonstrate high levels of accuracy in the classification and risk stratification of penicillin ADR labels using the reaction documented in the EHR. The model can be further optimised by incorporating additional training data and using transfer learning. Practical applications include automating case detection for penicillin allergy delabelling programmes.

A successful desensitization in an adult patient with ARA-C infusion reaction.

INTRODUCTION: Cytarabine (ARA-C) is an antimetabolite agent used especially in the treatment of hematologic malignancies. Infusion reactions have an important place among the side effects that may occur due to treatment. Clinical findings of infusion reactions resemble allergic reactions. CASE REPORT: 47-year-old male patient with a diagnosis of B-cell Acute Lymphoblastic Leukaemia developed infusion reaction during ARA-C treatment. MANAGEMENT & OUTCOME: There was no alternative treatment option for his existing malignant disease, we decided ARA-C desensitization. DISCUSSION: We would like to describe a successful desensitization protocol in an adult patient who experienced a reaction during ARA-C infusion.

Premedication strategy in cetuximab rechallenge after Grade 2 hypersensitivity reactions.

INTRODUCTION: Cetuximab, an IgG1 monoclonal antibody, is utilized in the treatment of metastatic colorectal cancer and squamous cell head and neck cancers. Due to the risk of hypersensitivity reactions, standard premedication with a histamine-1 (H-1) antagonist is recommended prior to administration, however, there is less guidance for premedication strategies to assist with rechallenge after infusion reactions. Here, we describe two cases of successful cetuximab treatment after Grade 2 reactions, in addition to risk factors and proposed premedication strategies for successful rechallenge. CASE REPORT: Two patients who experienced Grade 2 hypersensitivity reactions were both successfully rechallenged with increased premedications 1-2 weeks after initial infusions. The first patient was a 56-year-old male diagnosed with metastatic colorectal cancer receiving cetuximab as part of a clinical trial. The second patient was a 73-year-old male diagnosed with head and neck cancer receiving cetuximab as part of standard of care concurrent with radiation. MANAGEMENT AND OUTCOME: Each patient was rechallenged with an increased premedication strategy including dexamethasone, famotidine, diphenhydramine, and acetaminophen in addition to reducing the infusion rate. Both patients either continued treatment or successfully completed therapy, without any additional infusion-related reactions. DISCUSSION: We aimed to review risk factors related to cetuximab infusion reactions and propose a premedication strategy for rechallenge postreaction. Known risk factors include male sex and the accumulation of cetuximab-specific IgE. These may be mitigated by the addition of increased premedication with dexamethasone and famotidine with concurrent reduced infusion rate.

Successful desensitization in a patient with recurrent anaplastic oligodendroglioma presenting with procarbazine-mediated anaphylaxis.

INTRODUCTION: Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4 reactions, rechallenge should be avoided, and the agent should be replaced, unless the treatment is curative, in which case the application of a desensitization protocol should be considered. We present a successful case of desensitization in procarbazine anaphylaxis. CASE REPORT: A 53-year-old male patient was diagnosed with recurrent anaplastic oligodendroglioblastoma. The patient received three cycles of procarbazine, lomustine, and vincristine chemotherapy for malignancy recurrence. In the fourth cycle, on the 12th day of procarbazine treatment, the patient developed anaphylaxis. Procarbazine was given together with premedication as part of the 12-step desensitization process, and the fourth cycle was successfully completed. MANAGEMENT AND OUTCOME: Procarbazine hypersensitivity reactions are observed less frequently than reactions to other chemotherapeutics. We presented a case of procarbazine-associated severe anaphylaxis that was able to continue procarbazine chemotherapy with successful desensitization. This case is important in terms of confirming the procarbazine desensitization protocol. DISCUSSION: In literature there is only one protocol developed was successfully applied in one patient with procarbazine anaphylaxis. In the current case, we took this protocol into consideration in the management of our patient. Following the use of this protocol, the patient was able to continue procarbazine chemotherapy successfully. Procarbazine anaphylaxis is rare, and more cases are needed to be reported to confirm the desensitization protocol and when to continue procarbazine treatment.