Interleukin-6 as a biomarker of hypersensitivity reactions in chemotherapeutics and monoclonal antibodies.

BACKGROUND: In recent years, a new type of immediate hypersensitivity reaction known as cytokine release began to emerge, and within this phenotype of reactions, interleukin-6 is the most frequently associated with the presence during drug administration. Chemotherapeutic agents (QT) and monoclonal antibodies. OBJECTIVE: Determine interleukin-6 levels in hypersensitivity reactions to QT and monoclonal antibodies. METHODS: Observational and prospective study that was carried out from March 1, 2021 to March 1, 2022 in a university hospital in northeastern Mexico. Symptoms, severity, interleukin-6 levels, and skin tests of hypersensitivity reaction were evaluated at QT and monoclonal antibodies. RESULTS: A total of 41 patients with oncological disease were included, the most frequent being ovarian cancer. Symptoms as initial hypersensitivity reaction were neuromuscular in taxanes and cutaneous in Platinums.41.5% presented elevation of interleukin-6, and it was found more frequently in presence of metastases. Positive skin tests were found more frequently in the carboplatin and doxorubicin groups. The most frequently presented phenotype was type I in paclitaxel, carboplatin, and doxorubicin, and mixed-reaction (type I and cytokine release) in oxaliplatin. CONCLUSION: With the increasing prevalence of hypersensitivity reactions to biologic and antineoplastic therapies, interleukin-6 should be recognized as a biomarker in immediate hypersensitivity reactions to QT and monoclonal antibodies.

Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies: Safety and efficacy of desensitization.

BACKGROUND: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations. OBJECTIVE: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization. METHODS: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients. RESULTS: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction. CONCLUSION: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment.

Complete metabolic response after carboplatin desensitization in Peritoneal Carcinomatosis.

INTRODUCTION: High-grade serous primary peritoneal cancer is highly sensitive to platinum-based chemotherapy with response rates above 80%. Incidence of immediate hypersensitivity reactions to carboplatin is estimated to be between 15% and 20%, usually seen after a mean of 6-8 infusions, with patients developing moderate to severe reactions. CASE REPORT: A 62-year-old female patient with stage IIIC primary high-grade serous carcinoma of the peritoneum was diagnosed and chemotherapy with carboplatin and Paclitaxel was indicated by the oncology service and patient shows response. At 6 months the patient returns, a new PET/CT reports progression of the disease. Carboplatin/paclitaxel cycles are restarted and in the eight cycle of carboplatin within 40 min of administration, she presented severe anaphylaxis with skin, pulmonary, cardiac and atypical symptoms. Infusion is suspended and intramuscular epinephrine with hydrocortisone and chlorphenamine are administered resolving symptoms. MANAGEMENT AND OUTCOME: Intradermal skin test with carboplatin at the concentration of 10 mg / ml (dilution 1: 100) was positive. Due to the symptoms presented and to continue the safe reintroduction to carboplatin, a 4 bag 16-step drug desensitization protocol was carried out at a total dose of 620 mg with no hypersensitivity reactions. DISCUSSION: Prolonged carboplatin use is associated with an increased incidence of carboplatin-related hypersensitivity reactions. And in patients that present hypersensitivity reactions, a safe and effective carboplatin desensitization protocol can be carried out to reach the administration of a full dose. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.

Desensitization to Brentuximab Vedotin after anaphylaxis in refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin (BV) is a monoclonal antibody that targets CD30 antigen. It is indicated for the treatment of CD30 + lymphomas and classical Hodgkin lymphoma (HL), including advanced (stage III-IV) untreated disease, relapsed/refractory disease, and consolidation after autologous hematopoietic stem cell transplantation. In clinical trials the incidence of a hypersensitivity reaction is 1.2%. CASES REPORT: We present 3 cases of patients with refractory HL and anaphylaxis to the administration of BV ( Table 1). Symptoms are analyzed using a grading system described by Brown (2004) and a desensitization protocol was performed with a total dose of 100 mg of BV in 4 solution bags with an initial concentration of 1:1000 of total dose for cases of severe anaphylaxis, and desensitization of 3 solution bags with baseline concentration of 1: 100 for cases of moderate anaphylaxis. MANAGEMENT & OUTCOME: Intradermal skin tests were positive. Before desensitization, premedication with methylprednisolone and chlorphenamine was administered, as well as fluid therapy with 0.9% physiological solution at 100 cc/hour at induction stage, 250 cc/hour at maintenance stage, and increased to 500 cc/hour in case of hypersensitivity reaction. DISCUSSION: Drug desensitization in 12 or 16 steps allows tolerable administration of brentuximab vedotin after moderate to severe anaphylaxis. The favorable response to treatment of these patients may indicate that desensitization is a viable strategy for patients with relapsed or refractory HL.

Harmonizing allergy care-integrated care pathways and multidisciplinary approaches.

There is a wide time gap between the publication of evidence and the application of new knowledge into routine clinical practice. The consequence is sub-optimal outcomes, particularly concerning for long-term relapsing/remitting conditions such as allergic diseases. In response, there has been a proliferation of published guidelines which systematically review evidence for the gold-standard management of most allergic disorders. However, this has not necessarily been followed by improved outcomes, partly due to a lack of coordination across the patient pathway. This has become known as the "second translational gap". A proposed solution is the development and implementation of integrated care pathways (ICPs) to optimize patient outcomes, with the notion that evidence-based medicine requires evidence-based implementation. ICP implementation is shown to improve short-term outcomes for acute conditions and routine surgery, including reduced length of hospital stay, improved documentation and improved patient safety. However, this improvement is not reflected in patient experience or patient-centered functional outcomes. The implementation of life-long, cost-effective interventions within comprehensive pathways requires a deep appreciation for complexity within allergy care. We promote an evidence-based methodology for the implementation of ICPs for allergic disorders in which all stakeholders in allergy care are positioned equally and encouraged to contribute, particularly patients and their caregivers. This evidence-based process commences with scoping the unmet needs, followed by stakeholder mapping. All stakeholders are invited to meetings to develop a common vision and mission through the generation of action/effect diagrams which helps build concordance across the agencies. Dividing the interventions into achievable steps and reviewing with plan/do/study/act cycles will gradually modify the pathway to achieve the best outcomes. While the management guidelines provide the core knowledge, the key component of implementation involves education, training, and support of all healthcare professionals (HCPs), patients and their caregivers. The pathways should define the level of competence required for each clinical task. It may be useful to leave the setting of care delivery or the specific HCP involved undefined to account for variable patterns of health service delivery as well as local socioeconomic, ethnic, environmental, and political imperatives. In all cases, where competence is exceeded, it is necessary to refer to the next stage in the pathway. The success and sustainability of ICPs would ideally be judged by patient experience, health outcomes, and health economics. We provide examples of successful programs, most notably from Finland, but recommend that further research is required in diverse settings to optimize outcomes worldwide.

Allergy education and training for physicians.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of "allergy" as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence  to manage  mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide.

Successful oxaliplatin desensitization protocol in a patient with colorectal metastatic cancer.

INTRODUCTION: Platinum compounds are frequently used for the treatment of colorectal cancer as initial chemotherapy. Oxaliplatin is a third-generation platinum used for the treatment of stage III colorectal cancer and is associated with hypersensitivity reactions. The incidence of hypersensitivity reaction is approximately 12%, with 1-2% of patients developing moderate to severe reactions. CASE REPORT: A 54-year-old male patient with stage III B colon cancer was diagnosed and chemotherapy with oxaliplatin was indicated by the oncology service. Within 20 min of the first cycle of oxaliplatin, he developed dyspnea, laryngeal spam, foreign body sensation in the throat, nausea, and diarrhea; therefore, the infusion of oxaliplatin was suspended, and intramuscular epinephrine was administered and intravenous hydrocortisone along with chlorpheniramine with adequate resolution of symptoms.Management and outcome: Intradermal skin test performed at the concentration of 5 mg/ml (dilution 1:100) was positive. Due to the symptoms presented we decided to perform desensitization to oxaliplatin (total dose: 250 mg) with three bags-12 steps protocol with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. DISCUSSION: Approximately 50% of patients who are exposed to oxaliplatin may have hypersensitivity despite premedication. Desensitization protocol induces tolerance to a drug temporarily and is dependent on continuous exposure.