CT-1060: Comparative Safety and Efficacy of Calcineurin Inhibitor (CNI)-Free vs CNI-Based GVHD Prophylaxis Following Allogeneic HCT: A Real-World TriNetX-Based Propensity-Matched Analysis
Year: 2025
Type: conference-abstract
Abstract: Background CNI-based regimens have long been standard for GVHD prophylaxis post allo-HCT. Emerging evidence supports the use of CNI-free strategies incorporating sirolimus and post-transplant cyclophosphamide. However, comparative data on long-term safety and efficacy remain limited. Methods We conducted a retrospective cohort study using the TriNetX US Collaborative Network (69 healthcare organizations). Adults (≥18 years) with hematologic malignancies who underwent allo-HCT in 2017–2025 were identified using ICD-10-CM and -PCS codes. Patients were categorized into two groups: those receiving CNI-based prophylaxis (tacrolimus/cyclosporine ± methotrexate/mycophenolate mofetil [MMF]) and those receiving CNI-free prophylaxis (sirolimus + MMF + post-transplant cyclophosphamide), based on RxNormcoded medication exposure within 100 days post-transplant. Propensity score matching (1:1) was performed on 205 CNI-free and 2,899 CNI-based patients, yielding 199 patients per arm. Outcomes were assessed over 730 days post index using risk analyses and Kaplan-Meier survival methods. Results CNI-free prophylaxis was associated with significantly lower incidence of GVHD (rate difference [RD], –26.6%, CI, –35.6 to –17.7, P < 0.001; RR, 0.662, CI, 0.570–0.770; HR, 0.592, CI 0.462–0.759, P = 0.000) and neutropenia (RD, –15.1%, CI, –24.7 to –5.4, P = 0.002; RR, 0.712, CI, 0.569–0.890; HR, 0.767, CI, 0.569–1.033, P = 0.004). Emergency department visits were also significantly reduced (RD, –12.1%, CI, –20.1 to –4.0, P = 0.004; RR, 0.571, CI, 0.388–0.842; HR, 0.615, CI, 0.398–0.949, P = 0.027). Conversely, all-cause mortality was significantly higher in the CNI-free arm (RD, 7.0%, CI, –2.4 to 16.5, P = 0.146; RR, 1.209, CI, 0.935–1.564; HR, 1.390, CI, 1.005–1.921, P = 0.045). Febrile neutropenia was more frequent in CNI-free patients (RD, 9.5%, CI, –0.1 to 19.2, P = 0.054; RR, 1.253, CI, 0.995–1.579; HR, 1.619, CI, 1.194–2.196, P = 0.002). Renal toxicity was less frequent with CNI-free prophylaxis (RD, –24.8%, CI, –36.8 to –12.9, P < 0.001; RR, 0.499, CI, 0.344–0.724; HR, 0.441, CI, 0.280–0.693, P = 0.000). No statistically significant differences were observed for relapse of hematologic malignancies, pleural effusion, pneumonia, sepsis, anemia, ventilation assistance, or hospital dependence. Conclusions CNI-free GVHD prophylaxis post allo-HCT demonstrated lower GVHD incidence and improved renal safety but was associated with higher mortality and febrile neutropenia. These findings suggest that while CNI-free regimens offer certain advantages, careful patient selection and infection surveillance are critical. Further prospective trials are warranted.
Authors: Pramod Singh, Abdul Rafae Faisal, Ahmed Sajid, Zainab Zaib Khan, Muhammad Faizan, Asad Zaman, Ahila Ali, Shaikh Muhammad Daniyal, Syed Zaeem Ahmed, Ali Shan Haffeez, Farva Zaib Khan, Kashif Amin, Henna Qadri
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,890
OpenAlex ID: W4413774329