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Abstract Background: Chronic graft-versus-host disease (cGVHD) is a leading cause of non-relapse mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Further investigation is needed to understand cGVHD risk, diagnostic features, and outcomes. Patient-reported outcomes (PROs) are important for characterizing the direct and indirect impact of cGVHD on patients, caregivers, and the healthcare system. THRIVE (NCT05919511) is a prospective, longitudinal observational study of patients at risk for cGVHD to describe the clinical course, burden, and practice patterns for cGVHD. THRIVE uses a novel app-based platform designed for rigorous collection of PROs related to symptoms, quality of life, and indirect costs to the healthcare system. We report preliminary patient demographics and clinical characteristics at study enrollment. Methods: THRIVE includes adults aged ≥18 years in the United States who were enrolled 90–180 days after allo-HCT. Follow-up is for 36 months at intervals determined by clinician standard practice; a virtual site is available for patients who return to community sites for follow-up. Presence or absence of GVHD symptoms, cGVHD therapies when applicable, and adverse events are captured in medical records at clinical visits every ~3 months. In all, 13 PROs are assessed (Cutaneous GVHD Questionnaire [CuGQ], General Anxiety Disorder [GAD-7], Lee Total Symptom Scale [TSS; 7-day], modified Frenchay Activities Index [mFAI], modified Patient-Generated Subjective Global Assessment [mPG-SGA], Oral Health Impact Profile [OHIP-14], Ocular Surface Disease Index [OSDI-12], Patient Health Questionnaire [PHQ-9], Patient-Reported Baseline Data [PRBD], Patient-Reported Caregiver Assessment [PRCA], Patient-Reported Economic, Income, and Insurance Data [PREIID], Patient-Reported Outcomes Measurement Information System–Sexual Function [PROMIS-SF], and Pulmonary GVHD Questionnaire [PulmGQ]). Patients are randomized to sequence groups to complete rotating sets of 4–5 PRO measures via digital platform, monthly (Year 1) then every 2 months (Years 2–3). Recruitment is ongoing (target, 1500 patients). Results: This interim report includes the first 340 patients enrolled in THRIVE (data cutoff: June 17, 2025) at 22 sites across the United States since August 1, 2023. Median (range) age was 60.5 (19–83) years (>70 years, n=60 [18%]). Most patients were male (n=190, 56%), White (n=276, 81%), and had college/graduate education (n=219, 64%). Underlying disease was malignant in 328 (96%) patients; most common malignancies requiring allo-HCT were acute myeloid leukemia (n=129, 38%), myelodysplastic syndrome (n=50, 15%), and acute lymphocytic leukemia (n=37, 11%). Most patients (n=212, 62%) were in complete remission at time of allo-HCT, 282 (83%) enrolled after their first allo-HCT, and median (range) time from allo-HCT to enrollment was 111 (77–211) days. Transplant source was most commonly peripheral blood stem cells (n=272, 80%) from unrelated (n=229, 67%) donors, of whom 169 (50%) were male. Overall, 188 (55%) patients had human leukocyte antigen identical HCT, 72 (21%) had mismatched HCT, and 55 (16%) had haploidentical HCT. Conditioning regimens were myeloablative for 177 (34%) patients, reduced intensity for 164 (48%), and non-myeloablative for 16 (5%). At data cutoff, 296 (87%) patients were continuing in THRIVE; 18/44 (41%) patients who discontinued were alive at discontinuation. There were 107 patients (31%) who developed acute GVHD before enrollment (grade I, n=52; grade II, n=35; grade III, n=9; grade IV, n=0; missing/unknown, n=11); 85 (79%) received systemic treatment for acute GVHD. Overall, 28 (8%) patients had cGVHD at enrollment (mild, n=25; moderate/severe, n=3). Organs affected by cGVHD were skin (n=13), eyes (n=4), and gastrointestinal tract (n=3). Conclusions: THRIVE aims to report on clinical practice for managing risk and treatment of cGVHD after allo-HCT in a prospective cohort of ~1500 patients in the United States for ≤3 years. Although real-world assessment of PROs can be associated with challenges including willingness to participate in an observational study and the collection of data without routine clinical visits, the virtual hybrid design is intended to improve patient access and facilitate data collection. In the 22 months since initiation, 340 patients have been enrolled at 22 sites, and the discontinuation rate is low.

Abstract Introduction: Axatilimab is an anti–colony-stimulating factor 1 receptor (CSF-1R) monoclonal antibody that targets monocytes and macrophages, key mediators of inflammation and fibrosis in chronic graft-versus-host disease (cGVHD). Axatilimab is approved by the US Food and Drug Administration at a dose of 0.3 mg/kg (up to a maximum dose of 35 mg) every 2 weeks (Q2W) for patients with cGVHD after ≥2 prior lines of therapy, based on results from the pivotal phase 2 AGAVE-201 clinical trial (NCT04710576). Patients treated with the 0.3 mg/kg Q2W dose in the AGAVE-201 study were able to transition to 0.6 mg/kg every 4 weeks (Q4W) dosing based on the investigator's discretion and per study protocol criteria. Aims: To describe the safety and feasibility of transition from axatilimab 0.3 mg/kg Q2W to 0.6 mg/kg Q4W dosing using data from AGAVE-201. Methods: Patients treated with axatilimab 0.3 mg/kg Q2W in AGAVE-201 who had their Cycle 7 assessment and achieved a partial or complete response (PR/CR) per National Institutes of Health criteria that was sustained for ≥20 weeks or had not progressed were able to change their dosing schedule to 0.6 mg/kg Q4W (without dose capping) per the study protocol and investigator discretion. Safety and treatment duration were assessed in this post hoc analysis; patients who received additional systemic therapies were excluded. The data cutoff was March 30, 2025. Results: In the first 6 treatment cycles, 59 of the 80 patients (73.8%) randomized to axatilimab 0.3 mg/kg Q2W had a response to treatment (primary endpoint). Of these 59 patients, 19 (32.2%) transitioned to 0.6 mg/kg Q4W dosing. Among these 19 patients, demographics (median [range] age, 50.0 [20–73] y; male, 63.2%) and baseline clinical characteristics (median [range] number of organs involved at baseline, 3.0 [2–8]; severe disease, 73.7%; prior use of ibrutinib, ruxolitinib, or belumosudil, 89.5%) were comparable to the full cohort initially randomized to 0.3 mg/kg Q2W. Overall response rate in the first 6 treatment cycles among the 19 patients who switched to 0.6 mg/kg Q4W was 94.7% (95% CI, 74.0%–99.9%; CR, 5.3%; PR, 89.5%); 1 patient had stable disease and thus was eligible to switch, per investigator discretion. Patients were on treatment for a median (range) of 20.9 (2–32) months after switching doses; 16 of 19 patients (84.2%) maintained the 0.6 mg/kg Q4W dose after dose switching. The safety profile for axatilimab was generally similar before and after the dosing change. After switching to 0.6 mg/kg Q4W, 10 patients (52.6%) had grade ≥3 treatment-emergent adverse events (TEAEs); pneumonia was the only grade ≥3 TEAE reported in >1 patient (n=2). TEAEs led to treatment interruptions in 4 patients (21.1%) and discontinuations in 3 patients (15.8%) after switching. The most common TEAEs after switching to 0.6 mg/kg Q4W were fatigue (n=5 [26.3%]), upper respiratory tract infection (n=5 [26.3%]), and headache (n=4 [21.1%]); 1 patient (5.3%) had an infusion-related reaction (n=1 [rash]). Incidences of on-target TEAEs were generally similar before and after the switch, including elevations in alanine aminotransferase (n=3 before switching and n=1 after) and amylase (n=0 and n=1).Conclusion: Transition to 0.6 mg/kg Q4W (without dose capping) is feasible and well tolerated in patients treated with axatilimab 0.3 mg/kg Q2W on the AGAVE-201 study. The Q4W dosing strategy at the 0.6 mg/kg dose identified no new safety signals. Patients had a prolonged duration of therapy, with a median of 20.9 months (1.7 y), and 84% of patients continued treatment, suggesting ongoing clinical benefit. These data provide evidence of the safety and feasibility of a 0.6 mg/kg Q4W dosing strategy in alignment with the AGAVE-201 protocol.

Abstract Background In the current Canadian treatment landscape for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), eligibility for autologous stem cell transplantation (ASCT) guides the choice of salvage treatment. CD19 chimeric antigen receptor T-cell (CAR-T) therapies have improved outcomes in patients with chemorefractory DLBCL, but access is limited to eligible patients. This subanalysis of the RE-MIND2 observational retrospective cohort study investigated treatment patterns for R/R DLBCL in Canada. Patients and methods Data from patients enrolled in RE-MIND2 treated between 2010 and 2020 at 2 Canadian centers were retrospectively collected from health records. Descriptive statistics were used to analyze baseline characteristics, treatment initiated, and duration of treatment by line of therapy. Results One hundred and nine patients were included; 74.2% of patients were eligible for ASCT as 2L therapy, and 45.4% received transplants. ASCT eligibility for third- (3L) and fourth-line (4L) therapy declined to 17.1% and 5.9%, respectively. Patients received a wide variety of treatments in 3 and 4L. CAR-T therapy became available in 3 and 4L by the end of 2019. Median durations of treatment were <2.6 months in all lines of therapy; median time to next treatment ranged from 3.4 months in 4L to 5.3 months in 2L. Conclusion Results of our study support that ASCT-ineligible patients have a poor prognosis with conventional salvage chemotherapy. Before the availability of novel immunotherapies, no apparent standard of care was observed for Canadian patients with R/R DLBCL who were ineligible for or did not receive ASCT, especially after 2L treatment.