Drug Desensitization Research Articles

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, is an effective targeted therapy for hormone receptor-positive (HR+), HER2-negative, advanced or metastatic breast cancer. While nonimmediate hypersensitivity reactions (NIHRs) have been reported, no imme-diate hypersensitivity reactions (IHRs) to abemaciclib have been documented to date. Here, we report the first successful desensitization protocol for a patient who developed IHR to abemaciclib. A 75-year-old female with stage II breast cancer underwent a partial mastec-tomy followed by chemotherapy. Abemaciclib was initiated as part of adjuvant treatment. One hour after the third dose, she presented to the emergency department with lip swelling and urticaria. Symptoms resolved following the administration of intravenous methylprednis-olone (0.5 mg/kg) and maleate pheniramine (45.5 mg/mL). Skin prick testing with abemaciclib was negative; however, a drug provocation test led to recurrence of urticaria at a cumula-tive dose of 150 mg. Given the clinical necessity of abemaciclib and the lack of alternatives, a 12-step desensitization protocol was implemented using 300 mg of abemaciclib dissolved in 100 mL of distilled water. The protocol was completed over 4 h, with no complications observed during the procedure or in the subsequent 3-month follow-up. The patient contin-ued abemaciclib at 300 mg/day without recurrence of symptoms. This case highlights the importance of drug desensitization in oncology, particularly in patients for whom no alterna-tive therapies are available.

Objective: Ustekinumab is a biological agent used in the treatment of inflammatory diseases. Since biological therapies are targeted therapies, their use is increasing and the incidence of related reactions is increasing accordingly. We present this case because of the successful desensitization we applied to a patient who developed a reaction to ustekinumab. Materials and methods: An adult Crohn's disease patient who experienced an adverse reaction to the fifth subcutaneous dose of ustekinumab was evaluated in our Immunology and Allergy clinic. Results: The patient was successfully treated using the stepwise rapid drug desensitization protocol. Conclusion: We present this case to emphasize the importance and awareness of desensitization in managing drug reactions in clinics such as Dermatology, Rheumatology and Gastroenterology where the drug is widely used.

Progressive Decrease in Interleukin 6 Levels After Successive Doses of Avelumab in a Rapid Drug Desensitization Protocol.

73 Background: Hypersensitivity reactions (HSR) to antineoplastics pose significant challenges in cancer treatment. These reactions can often be managed via rapid drug desensitization (RDD), or introduction of the drug at increasing doses to promote temporary immune tolerance. RDD requires dedicated monitoring and has historically been limited to the intensive care unit (ICU), where bed availability is limited. Emerging data suggests it may be safe and effective to move RDD outpatient. We implemented a multidisciplinary team of allergists, oncologists, and pharmacists to develop a new workflow to transition RDD from the ICU to the oncology stepdown unit (SDU) and then the outpatient infusion center. Methods: We examined the data of eligible patients undergoing RDD at Columbia University Medical Center from 2022-2024, before and after implementation of the new workflow. Included patients had a cancer diagnosis and a suspected HSR during antineoplastic infusion. HSRs were reviewed by an allergist and classified as mild (absence of chest pain, blood pressure changes, dyspnea, oxygen desaturation, or throat tightness) or severe (≥1 of these). Data collected included the oncologic diagnosis, culprit agents, cycle number at initial HSR, date(s) and location(s) of RDD, and severity and management of breakthrough reactions. A two-tailed z-test assessed differences between groups. Results: During the study period, 26 patients underwent 102 RDDs. Mean age at initial RDD was 57.7 years (SD 12.5), and 69.2% were female. The most common diagnoses were pancreatic cancer (23.1%) and colorectal cancer (15.4%); the most common culprit for an initial HSR was oxaliplatin (42.3%); and 34.6% of the initial HSRs were classified as mild, 65.4% as severe. Forty-six total RDDs were performed prior to the new workflow and 56 after. Prior, 16/46 (34.8%) encounters took place in the ICU, 24/46 (52.2%) on SDU, and 6/46 (13.0%) outpatient. After the new workflow, zero took place in the ICU, 19/56 (33.9%) on SDU, and 37/56 (66.1%) outpatient, demonstrating a significant decrease in ICU utilization (p < 0.00001). While undergoing RDD, 22 total breakthrough reactions occurred out of 102 total encounters; 21 were classified as mild (most commonly cutaneous reactions such as urticaria), while one was severe. In 99/102 (97.1%) encounters, the RDD protocol was successfully completed. There was no difference in frequency of breakthrough reaction (p = 0.31) or RDD completion after breakthrough (p = 0.67) between the workflow groups. Conclusions: Our data supports that RDD is an effective method for achieving temporary tolerance and safely administrating antineoplastic treatment that otherwise would need to be discontinued. By implementing a standardized process for HSR identification and treatment we safely transitioned out of the ICU, which may optimize resource utilization, access to care, and cost reduction.

Update on desensitization to chemotherapeutics and biologicals.

Various adverse reactions to elexacaftor/tezacaftor/ivacaftor (ETI) therapy have been documented in the literature. Here, we present the first reported case in Croatia of severe rash following ETI therapy in a 19-year-old female cystic fibrosis (CF) patient. There were two attempts to introduce ETI therapy, spaced two months apart, both of which resulted in diffuse maculopapular rash, in the second attempt, the rash appeared on the same day as re-initiation. Given the clinical benefits of ETI treatment, andinspired by several case reports on drug desensitization, in July 2023, we started the patient on a modified 3-day-tolerance induction protocol which was successful.

We present a case of a 41-year-old female diagnosed with Granulosa Cell Tumor (GCT) EC IVB who developed a hypersensitivity reaction (HSR) to carboplatin during the sixth cycle of treatment and subsequently underwent successful intraperitoneal desensitization with cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC). The patient experienced a severe HSR 30 min after carboplatin infusion, presenting with generalized rash, pruritus, nausea, chest pain, and dyspnea. The infusion was halted, and she was treated with intramuscular epinephrine (0.50 mg), intravenous chloropyramine (20 mg), and 250 mL saline, resolving symptoms. Platinum skin tests were subsequently performed and yielded negative results for carboplatin, cisplatin, and oxaliplatin. Following multidisciplinary consensus, cytoreductive surgery with HIPEC and intraperitoneal desensitization to cisplatin was planned. The patient had a peritoneal carcinomatosis index (PCI) of 17. Cytoreductive surgery included omentectomy, appendectomy, resection of mesenteric implants, diaphragmatic and parietal peritonectomy, in bloc hysterectomy, bilateral salpingo-oophorectomy, and pelvic peritonectomy, achieving a completeness of cytoreduction (CC-0). HIPEC was performed with cisplatin (100 mg/m²) at 42°C for 140 min. A desensitization protocol with intraperitoneal cisplatin (180 mg in 8 incremental steps over 140 min) was successfully completed without adverse reactions. Platinum-based chemotherapeutics are frequently associated with HSR, with increasing incidence upon repeated exposure. Intraperitoneal administration, as in HIPEC, may reduce systemic hypersensitivity risks. While prior cases have demonstrated safe HIPEC administration of cisplatin in patients with oxaliplatin-induced HSR, no documented cases exist of intraperitoneal drug desensitization in this context. Our case suggests that intraperitoneal desensitization with cisplatin may be a viable alternative for patients with systemic HSR to platinum agents. Further research is required to establish safety protocols, cross-reactivity risks, and efficacy outcomes for this approach.

Rapid desensitization in patients with immediate hypersensitivity to antineoplastic drugs: Clinical outcomes and risk factors.

Rapid drug desensitization (RDD) is the cornerstone of managing patients with immediate drug hypersensitivity reactions (IDHR) to antineoplastic drugs in Southern Europe and the United States. As the first in Northern Europe, an allergy treatment program that includes RDD and drug provocation testing (DPT) was implemented for Danish patients with cancer. We report the results of this allergy intervention, the number of successful treatments, the fraction, timing and severity of breakthrough reactions (BTR) and the actual treatment duration of RDD procedures. This was a prospective observational study. Patients with IDHRs to antineoplastic drugs referred to the allergy treatment program were included. Patients were followed up until finalization of DPT and/or RDD. RDDs were performed according to one-bag RDD-protocols with drug concentrations strictly following manufacturer's instructions and infusion sets primed with flushing fluid. The outcome of DPTs and RDDs were recorded together with detailed information on BTRs and treatment duration of RDD-procedures. During 28months, 72 patients were included. With DPT, a safe drug alternative was found for five drugs, hypersensitivity was ruled out for six, and one treatment was discontinued after a positive DPT. RDD was performed in 60 patients. Of 248 initiated RDD procedures, 247 were completed. BTRs were observed in 53% of patients and 27% of RDD-procedures, with most BTRs being mild to moderate. The treatment duration was below 6hours in 96% of RDD procedures. The allergy treatment program, which included DPT and one-bag RDD-protocols, allowed patients to continue critical antineoplastic treatments despite IDHRs.

All chemotherapy agents have the potential risk of developing hypersensitivity reactions (HSRs). In patients who develop HSRs, rapid drug desensitization (RDD) enables the use of a treatment option that prevents disease progression. If RDD fails to elicit the desired results or in patients with baseline HSRs Brown grades 2-3, omalizumab may also be a treatment option. Our primary aim is to share the demographic and clinical characteristics of our patients who underwent RDD. Our secondary aim is to share our experience with omalizumab during RDD in difficult cases. This was a retrospective study of patients with immediate-HSRs to chemotherapeutic (CHT) agents. Initial HSRs were classified as grades 1, 2, or 3 based on severity. Prick/intradermal skin tests were performed with implicated agents. In grade 3 reactions and skin prick test (SPT)-positive patients, a 16-step desensitization was applied. A 12-step desensitization was applied in other patients. In 10 patients, omalizumab was administered for premedication. The study analyzed data from 80 patients (F/M: 60/20). The number of patients who received different medictions was as follows: carboplatin-23, paclitaxel-22, oxaliplatin-21, dasotaxel-9, etoposide-1, docorubicin-1, pertuzimab-1, paclitaxel+herceptin-1, and bevacizumab+oxaliplatin-1. Inıtıal HSRs were grade 1: 27(%33,7) , grade 2: 30 (%37,5), and grade 3: 23(% 28,7). A total of 22 patients (27.5 %) had atopy based on SPT. Skin tests with implicated agents were done on 78 patients. For the inıtial HSR grades 1, 2, and 3, the number of positive skin test responses was 25/27, 27/29, and 17/22, respectively. A total of 377 RDDs were performed completely, but 22 patients developed 3 reactions during RDD (grade 1: 77.2%, grade 2: 13.6%, and grade 3 9%). All patients received a mean of 4.7 (minimum: 1, maximum: 23) RDDs. There was no statistical difference in the severity of reaction, system involvement, and distribution of symptoms between platinum and taxanes groups. The rate of reaction during RDD was higher in patients receiving platinum compared with taxan. Ten patients received omalizumab before RDD. Initial HSRs were grade 3 in 8 patients; the responsible agent was platinum in 5 patients; and 1 patient developed grade 3 HSR during RDD. In four patients, ınıtıal HSRs were grades 2 and 3, and desensitization was not continued when HSR developed during RDD. A total of 373 successful RDDs were performed. RDD is a very important treatment applied to patients with immediate-HSRs to CHT agents. Omalizumab facilitated the continuation of chemotherapy in patients with index reaction grades 2-3. It provided an opportunity for 8 of 10 patients with Grade 2-3 severe reactions to continue treatment. In our population, 98.9% (373/377) successful completion of RDDs in all chemotherapy groups demonstrates the safety of this procedure.

Comparison of three-bag and single-bag protocols in rapid drug desensitization with chemotherapeutic and biological agents.

One-bag protocol for cancer drug hypersensitivity: A meta-analysis of safety and effectiveness.

Background: Rapid drug desensitizations (RDD) provide a means for patients with a history of acute hypersensitivity reactions (HSR) to platinum-based chemotherapeutics to continue their first-line oncologic treatment. Approximately one third of RDDs have been associated with breakthrough reactions (BTR) but identifying which patients are at risk is challenging. Objective: The objective was to identify factors predictive of patients at risk of developing BTR during their initial RDD. Methods: Forty-three patients who developed HSRs to a platinum drug and subsequently underwent RDDs were included for analysis. A retrospective manual chart review was performed to obtain demographics and information with regard to oncologic history, incident HSR, and RDD. The severity of HSRs and BTRs was determined by using the Brown criteria. Results: BTRs developed in 37% of patients during their initial RDD. Compared with those who tolerated RDDs, the patients who developed BTRs were significantly more likely to have positive allergy skin test results with a platinum drug (100%) than those who tolerated their RDD (47%, p = 0.01). The median (interquartile range) time between incident HSR and initial RDD was significantly shorter among patients who developed BTRs (31 days [21-49 days]) than those who did not develop BTRs (46 days [28-826 days]) (p = 0.04). Only 46% of patients with severe incident HSRs developed a BTR. However, severe BTRs occurred only in patients who had severe incident HSRs (p = 0.02). Conclusion: Severe clinical signs and symptoms of incident HSRs do not always predict if BTRs will occur during initial RDDs. However, patients with severe BTRs are more likely to have had a severe incident HSR.

The increasing use of biologics in cancer treatment is associated with an increase in drug-related hypersensitivity reactions (HSR) of varying severity. Pembrolizumab is a humanized monoclonal antibody specifically targeting the programmed cell death protein 1 (PD-1) receptor, largely used in lung cancer and other malignancies. Pembrolizumab-related HSR has rarely been described, with very few reported positive allergy tests.We describe the case of a 77-year-old man treated for metastatic lung adenocarcinoma, who presented a severe anaphylactic reaction during the 8th pembrolizumab administration. Allergy tests confirmed the type I IgE-mediated hypersensitivity mechanism.Based on the four published cases, immediate HSR induced by pembrolizumab can occur after several treatment courses with potentially severe anaphylactic reactions. Mild symptoms during the preceding courses might occur and should be monitored. Skin tests are reliable, safe, and useful to guide management. When immediate HSR induced by pembrolizumab is confirmed, rapid drug desensitization may be considered. Further studies are needed to identify risk factors for immediate HSR induced by pembrolizumab.

e23326 Background: Platinum compounds carry a significant risk of hypersensitivity reactions (HSR), and repeated exposures can lead to IgE-mediated sensitization, culminating in allergic symptoms and anaphylaxis. Drug desensitization offers a temporary immunological tolerance, allowing for the safe reintroduction of platinum-based therapies in allergic individuals. Methods: To evaluate the safety and effectiveness of rapid drug desensitization (RDD) for platinum-related hypersensitivity reactions, we conducted a systematic review. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered our study in PROSPERO (CRD42023473211). A thorough literature search was performed across the Medline, Embase, Web of Science, and Scopus databases. Results: A total of 53 studies were included (n = 2853) from 11 countries between 1998 and 2024, patients with initial HSR to platinums, carboplatin (n = 44), oxaliplatin (n = 30) and cisplatin (n = 23) that underwent a desensitization. The symptoms of HSR to platinum were skin and respiratory. There was variability in the type of desensitization protocols used, the most frequent being 4 bags-4 steps and 3-4 bags and 12-16 steps, with an average duration of 5.7 2.5 hours. Premedication was reported in most cases (n = 49), consisting mainly of antihistamines, corticosteroids and leukotriene antagonists. Patients tolerated the desensitization protocol; the success rate at desensitization with carboplatin and oxaliplatin varied between 67-100%, while it was 100% in all cases of desensitization for cisplatin. An incidence of HSR during desensitization was reported, ranging from 4.4% to 96.7% (median of 24%), and no associated deaths. Conclusions: Rapid drug desensitization (RDD) is an effective procedure for patients with platinum-induced hypersensitivity reactions, enabling safe re-exposure to carboplatin, cisplatin, and oxaliplatin, thereby improving quality of life and ensuring the continuation of first-line therapy.

11057 Background: Hypersensitivity reactions (HSRs) are a significant challenge in oncology, often leading to treatment modifications or interruptions. Rapid Drug Desensitization (RDD) is a method to reintroduce chemotherapeutic agents and monoclonal antibodies in patients with previous HSRs. This study focuses on safety, comparing the severity of initial HSRs with breakthrough reactions (BTRs) during desensitization. Methods: An observational, ambispective study was conducted from August 2020 to August 2024 at the University Hospital in Mexico. Patients with HSRs underwent RDD using a 12-step, 3-bag protocol. HSR severity was classified using Brown’s scale. The primary endpoint was BTR severity compared to initial reactions, with secondary endpoints assessing BTR frequency and RDD completion rates. Data were sourced from electronic medical records under a protocol reviewed and approved by the hospital's research ethics committee. Inclusion required documentation of HSRs, the need to continue treatment with the implicated drug, and completion of the RDD protocol. Missing severity data were inferred from clinical notes or excluded. Chi-square tests compared severity grades (mild, moderate, severe) between initial reactions and BTRs, including cases without reactions for comprehensive analysis. Proportional frequencies were applied to address the difference in sample size. Results: A total of 927 RDD procedures were performed in 219 patients, with 84% female and a median age of 43 years. The severity of initial reactions was classified as mild in 12.1%, moderate in 43.3%, and severe in 44.6%. During the 927 desensitizations, breakthrough reactions occurred in only 8.6% of cases, distributed as mild (4.5%), moderate (1.8%), and severe (2.3%). Chi-square analysis confirmed a statistically significant difference in severity distribution between initial HSRs and BTRs (χ² = 834.72, p < 0.0001). This demonstrated a substantial reduction in severity for BTRs compared to initial reactions. Despite the occurrence of BTRs, all patients completed the RDD protocol, received the full therapeutic dose, and no fatalities were reported. Conclusions: The comparison between initial HSRs and breakthrough reactions during RDD highlights the distinct nature of these events: initial HSRs represent baseline sensitivity, whereas BTRs occur as controlled outcomes during desensitization. The analysis confirms that desensitization is a safe and effective tool in oncology, significantly reducing both the frequency and severity of breakthrough reactions compared to initial reactions, ensuring treatment continuity and minimizing risks for patients. Severity distribution of initial HSRs and BTRs. Severity Mild (%) Moderate (%) Severe (%) Total (%) Reference Population Initial HSRs 27 (12.3) 95 (43.3) 97 (44.2) 219 (100) 219 patients BTRs 42 (4.5) 17 (1.8) 21 (2.3) 80 (8.6) 927 desensitizations

Long-Term Efficacy and Safety of Benralizumab Treatment for PDGFRA-Negative Hypereosinophilic Syndrome.

New Approaches to Chemotherapeutic Drug Allergy: From Drug Challenge to Desensitization.

Background: Rapid drug desensitization (RDD) is a procedure that provides temporary tolerance to chemotherapeutics for appropriate patients who experience hypersensitivity reactions (HSR), which allow them to continue their treatments. Due to the labor-intensive and time-consuming nature of the commonly used multiple-bag RDD procedure, there is a need to develop an alternative protocol. We aimed to share our experiences with single-bag RDD in patients experiencing HSRs with chemotherapeutics. Methods: The study was conducted by retrospectively reviewing the files of patients who experienced immediate-type HSRs to chemotherapeutics and underwent single-bag RDD. The severity of HSRs was classified according to the Brown grading system. Prick and/or intradermal skin tests were performed with the relevant agents. The protocols were applied as a single-bag, 12-step process. Results: The study comprised 46 patients (women/men, 35/11; mean ± standard deviation age, 55.9 ± 11.9 years; 27 HSRs to platinums; 16 HSRs to taxanes; and 3 HSRs to biologic agents). Nine patients (19.6%) had an initial HSR of grade 1, 26 patients (56.5%) had an initial HSR of grade 2, and 11 patients (23.9%) had an initial HSR of grade 3. The skin testing result with the responsible drug was positive in 15 of 42 (35.7%), and the rate of positive responses in patients with grade 1, 2, and 3 initial HSRs was 37.5%, 33.3%, and 40%, respectively. A total of 163 single-bag RDDs procedures were performed, and 17 breakthrough reactions (BTR) occurred during the procedure (five of these reactions [29.5%] were grade 1; nine [53.9%] were grade 2; three [17.6%] were grade 3). Of these BTRs, 16 occurred with platinums and one with rituximab; no BTRs were observed with taxanes. In conclusion, 99.3% of the total 163 single-bag RDD procedures were successfully completed. Conclusion: Our experience indicates that single-bag RDD can be a safe and effective alternative that saves time and labor in appropriate patients.

Immediate drug hypersensitivity reactions (IDHRs) complicate the treatment of patients with cancer. Rapid drug desensitization (RDD) is not a standard treatment option in Northern Europe as in Southern Europe and the US. Thus, in Denmark, allergists are not involved when cancer treatments are complicated by IDHRs. The purpose was to investigate whether Danish patients could benefit from the implementation of an allergy work-up including RDD by investigating the magnitude of the problem with IDHRs in Danish antineoplastic drug therapy, in addition to describe characteristics of IDHRs, re-treatment strategies, and outcomes. This prospective observational single-center study was conducted at a large university hospital. Patients were included over 17 months. Patients were interviewed during index reaction. Information on culprit drug, infusion procedure, and premedication was obtained, together with reaction phenotype and severity. After 3 months, information on re-treatment strategies and outcome were obtained from medical records. In total, 126 patients experienced IDHRs during the study period. This corresponds to 2.5% of patients receiving antineoplastic drug therapy. Re-treatment, using increased premedication and/or decreased infusion rate, was attempted in 97 patients and tolerated by 69. However, 57 out of 126 patients (45%) discontinued treatment. This corresponds to 1.1% of patients receiving antineoplastic drug therapy. Patients with gynecologic cancers had a particularly high risk. IDHRs are infrequent in antineoplastic drug therapy, but due to the large number of patients with cancer, the number of IDHRs is significant. Patients discontinuing treatment could benefit from an allergy work-up including RDD.