Progressive risk of carboplatin immediate-type hypersensitivity in gynaecological malignancies in Chinese: A 3-year longitudinal outcome study

Introduction Gynaecological malignancies rank among the leading causes of cancer-related mortality in women worldwide, with the majority of cases diagnosed at advanced stages and associated with high recurrence rates 1. In Asian populations, particularly among Chinese, the incidence and mortality rates have shown a steady rise over the past decade. This is particularly evident in ovarian cancer, with the majority deemed surgically unresectable 2. Consequently, effective chemotherapeutic agents have become essential for these patients. Platinum-based agents, such as carboplatin, serve as the cornerstone and first-line treatment for advanced gynaecological malignancies. However, immediate-type hypersensitivity reactions (IHSR), including anaphylaxis, to platinum compounds are frequent following repeated exposure, which restricts patients from this life-saving therapy 3. This problem is most pronounced in regions lacking adequate drug allergy services, such as Hong Kong 4,5. While substantial research has been conducted in Western countries, studies in Asia have primarily focused only on ovarian cancer, with limited epidemiological data available for other gynaecological malignancies 6. Understanding patterns of hypersensitivity is critical to ensuring uninterrupted treatment and patient outcomes. Therefore, we conducted this longitudinal outcome study for gynaecological malignancies over a 3-year period in Hong Kong. 2. Materials and methods We enrolled all patients diagnosed with newly diagnosed gynaecological malignancies at Queen Mary Hospital, a tertiary center specialized in gynaecological oncology, who received carboplatin-based chemotherapy starting from January 2021 and were followed longitudinally until December 2023. For this study, a “chemotherapy cycle” was defined as a single carboplatin dose within a treatment regimen. Per institutional protocol, 1 course of chemotherapy comprised 6 such cycles. Board-certified Specialists in Immunology HSR, hypersensitivity reactions.Among the 183 patients in the longitudinal cohort, the overall IHSR incidence rate was 8.7% (16/183). 83% (151/183) achieved a complete response after the first treatment cycle (CR1). Of these, 46% (69/151) experienced relapse, and 81% (55/69) received a second course of carboplatin-based chemotherapy. Among those retreated, 47% (26/55) achieved a second complete response (CR2). Of these, 54% (14/26) relapsed again, and 71% (10/14) underwent a third course, with 30% (3/10) achieving complete response (CR3). Time-to-event analysis by Kaplan–Meier is shown in Supplementary Table S3, Supplemental digital content 1, https://links.lww.com/PA9/A96 and Figure 2. A progressive decline in IHSR-free probability with increasing cumulative carboplatin exposure was observed (from 13.5% after 12 cycles, to 25.1% by 18 cycles, and 40.1% by 24 cycles).Figure 2.: Kaplan–Meier estimate of time to first carboplatin immediate hypersensitivity reaction. IHSR, immediate-type hypersensitivity reactions.Overall, 19% (34/183) experienced chemotherapy-related ADR, with 47% (16/34) classified as allergic, of which 69% patients experienced systemic involvement (grade 2–3). Details of these patients and reactions are summarized in Supplementary Table S2, Supplemental digital content 1, https://links.lww.com/PA9/A96. No patients were re-treated with other platinum-based chemotherapies. Among patients with confirmed chemotherapy hypersensitivity, diagnoses were established by clinical history review in 14 cases, by positive intradermal skin testing in 1 case, and by positive drug provocation testing in 1 case. Incidence of carboplatin IHSR progressed with additional cycles of chemotherapy exposure, from 0.4% (1/183) in the first cycle to 22% (12/55) in the second and 30% (3/10) in the third. The number of chemotherapy cycle exposure (94% vs. 30%, P < 0.001) and history of relapse (13 range, 8–43 vs. 6 range, 1–41, P < 0.001) were significantly associated with the incidence of carboplatin IHSR. The median number of carboplatin doses before development of IHSR was 10.5 (range, 7–23). Further exploratory multivariate analysis using Firth logistic regression was performed (Supplementary Table S4, Supplemental digital content 1, https://links.lww.com/PA9/A96). Relapse history remained independently associated with carboplatin IHSR (adjusted odds ratio OR, 12.55; 95% CI, 2.38–66.11; P = 0.003). In contrast, cumulative carboplatin exposure demonstrated a borderline association that did not reach statistical significance (adjusted OR, 1.08 per cycle; 95% CI, 0.99–1.19; P = 0.079). 4. Discussion This study represents one of the largest longitudinal outcome cohorts on carboplatin IHSR in patients with gynaecological malignancies in Asia. We identified a particularly high incidence among patients with disease relapse and exposure to ≥2 cycles (median 10 doses). Time-to-event analysis further demonstrated a progressive increase in cumulative IHSR risk with increasing carboplatin exposure, consistent with other international cohorts 6,8. In the majority of cases, diagnosis was established through a detailed review of clinical history when further testing was not clinically feasible, reflecting real-world practice in settings without a structured allergy pathway integrated into oncology care. Notably, because of the initial lack of formal access to allergy services, some patients continued treatment despite experiencing carboplatin-associated IHSR, resulting in more severe reactions during subsequent cycles 4,5. These findings reflect a clinically significant pattern observed in other populations yet rarely documented in Asian cohorts. Furthermore, there was a notably high prevalence of drug allergy labels (approximately double that of the general population) with disproportionately higher rates of reported allergies to iodinated contrast media and NSAID 9,10. These medications are particularly important in the care of cancer patients, as iodinated contrast media are essential for diagnostic imaging and NSAIDs are commonly used for pain management and inflammation control. Inaccurate allergy labeling may therefore lead to unnecessary medication avoidance, limiting analgesic options, increasing reliance on opioids, and hindering effective disease monitoring. These observations call for enhanced multidisciplinary efforts and broader access to drug allergy education and services, particularly chemotherapy desensitization 11,12. Such programs could be developed by drawing on the experience of other multidisciplinary drug allergy services in other specialties that have demonstrated notable success in the region 13–17. Limitations of this study mainly stem from its observational nature. Decisions on subsequent therapy following IHSR (switching agents, desensitization, or palliation) were predominantly decided based on the joint decision of patients and gynaecological oncologists. More granular data on disease and ADR beyond those to carboplatin were not available. The small number of hypersensitivity events limited the statistical power of our multivariate analysis. Per-protocol cohort analysis of progressive IHSR risk may introduce selection bias. Despite these limitations, this study provides unique longitudinal data on the progressive nature of carboplatin IHSR risk in a well-characterized cohort, with rigorous allergist-confirmed outcomes. In conclusion, our study highlights the progressive risk of carboplatin IHSR in Asian women with gynaecological malignancies, particularly among those with disease relapse and greater exposure to carboplatin. These findings underscore the urgent need for enhanced drug allergy services and integration of multidisciplinary initiatives into oncological care.