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Abstract Background In patients with myelofibrosis (MF) undergoing allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD) prophylaxis has traditionally included a calcineurin inhibitor (CNI) plus methotrexate (MTX). We conducted a retrospective study comparing the safety and efficacy of post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to CNI-based regimens. Methods This study was approved by the Mayo Clinic IRB. Patients with myelofibrosis who underwent allo-HCT after 2016 at Mayo Clinic in Arizona and Florida were included. Categorical variables were compared using Chi-square or Fisher's exact tests. Overall survival (OS) was defined from transplant to death, and progression-free survival (PFS) from transplant to relapse or death. OS and PFS were estimated using Kaplan-Meier methods; univariate differences were assessed with log-rank tests. The cumulative incidence of acute and chronic GVHD and time to neutrophil and platelet engraftment were analyzed using competing risk models, with death as a competing event; differences were tested using Gray's test. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Results A total of 110 patients were included. 53 patients received PTCy-based prophylaxis (43 PTCy/Tac/MMF, 1 PTCy/CSA/MMF, 9 PTCy/Siro/MMF), while 57 received non-PTCy regimens (54 Tac/MTX +/- 39 T-cell depletion, 2 CSA/MMF, 1 Tac/MMF). Median age at transplant was 63 (range: PTCy 40-76; others 38-74) years in both groups; 59 were male (58.5% PTCy vs 49.1% others). Median Karnofsky Performance Status (KPS) and HCT–Comorbidity Index (HCT-CI) in patients receiving PTCy vs non-PTCy were 90 vs 80 and 1 vs 3, respectively. Conditioning intensity was similar: 22.6% myeloablative vs 21.7%, and 77.4% reduced-intensity vs 76.7% in PTCy and non-PTCy, respectively (p=1.000). Stem cell source was peripheral blood in all patients except one in the non-PTCy group who received bone marrow. 58 patients had primary MF (54.7% PTCy vs 50.9% others), and 52 had secondary MF (45.3% PTCy vs 49.1% others), including essential thrombocythemia (28.3% PTCy vs 31.6% others), polycythemia vera (17.0% vs 15.8%), and MPN-NOS (0% vs 1.8%). Median follow-up was 26.2 months (95% CI: 20.7-52.7) in the PTCy and 60.6 months (95% CI: 53.1-70.6) in the non-PTCy cohort. CD3 and CD33 donor chimerism ≥95% at day +100 was 66.7% and 86.7% in PTCy vs 63.6% and 92.7% in others, respectively (p=0.50); day +100 driver molecular mutations were present in 32.1% of PTCy and 32.0% of others (p>0.99). Rates of acute GVHD grades ≥2 and ≥3 were not statistically significant, in the PTCy group (37.7% vs 49.1% p=0.229 and 17.0% vs 22.8% p=0.445, respectively). Chronic GVHD (any grade) occurred in 42.3% of PTCy vs 38.2% of others (p=0.664), while moderate-to-severe cGVHD was lower with PTCy (21.2% vs 27.3% p=0.461). Platelet engraftment was significantly delayed in the PTCy group (median 33 vs 21 days, p=0.030). Median time to neutrophil engraftment was also delayed in the PTCy group (20 vs 17 days, adjusted p=0.025). Age-adjusted HR for time to platelet engraftment was 0.60 (95% CI: 0.41–0.90; p=0.014), and for neutrophil engraftment 0.65 (95% CI: 0.44–0.95; p=0.025), indicating significantly delayed hematopoietic recovery with PTCy. Graft failure occurred in 9.4% vs 5.3% (p = 0.48); primary 7.5% vs 3.5%, secondary 1.9% vs 1.8% in PTCy vs non-PTCy groups, respectively. Relapse or progression occurred in 11.3% of PTCy vs 17.5% of others (p=0.355); four patients in the non-PTCy group progressed to AML post-transplant, versus none in the PTCy group (p=0.119). 1-year TRM was 22.6% in the PTCy group and 14.0% in the non-PTCy group, p = 0.324. Median OS was 72.8 months in the PTCy group (95% CI: 49.9 months, upper limit not estimable [NE]) and 93.4 months in the non-PTCy group (95% CI: 48.5 months, upper limit NE), although the difference was not statistically significant (p=0.739). After adjusting for age and HCT-CI, there were no significant differences in PFS (adjusted HR 1.37; 95% CI: 0.73–2.56; p=0.331) or OS (adjusted HR 1.27; 95% CI: 0.64–2.51; p=0.498). Conclusions In myelofibrosis patients undergoing allo-HCT, PTCy-based GVHD prophylaxis showed similar rates of grade ≥2 acute and moderate-severe chronic GVHD compared to non-PTCy regimens. Engraftment was significantly delayed, while OS and PFS were comparable. PTCy appears to be a safe and viable alternative to CNI-based prophylaxis.

Abstract Introduction Survival following allogeneic hematopoietic cell transplantation (allo-HCT) has improved over the last several decades. Implementation of reduced-intensity conditioning and improvement in graft selection, graft vs. host disease (GVHD) prophylaxis and treatment, and infection disease management, among others, have contributed to reducing non-relapse mortality (NRM). The use of post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis, in particular, has been associated with reduced incidence of acute and chronic GVHD in both HLA-matched related and matched unrelated donor allografts. In this study, we aim to determine prognostic factors for NRM (including early NRM defined as within 100 days post-transplantation), disease-related mortality (DRM), and overall survival (OS) in a large cohort of patients following allo-HCT. Methods Patients who received consecutive allo-HCT at our institution from 2009-2023 were included. Clinical data were collected from retrospective reviews of the electronic medical records. Patient- and transplant-related variables were compared between patients who died and those who were alive at 100 days post allo-HCT. Univariate and multivariate Cox proportional hazard models were used to identify prognostic associations between risk factors and OS. Kaplan-Meier method was used to evaluate OS. Log-rank test was used to compare OS between groups. Statistical significance was set to < 0.05. Results A total of 536 patients (male=285, 53%) were included. Median age at time of allo-HCT was 59 (range, 19-75) years. Most patients were White/Caucasian (n=232, 86%). The most common diagnoses included acute myeloid leukemia (AML) (n=110, 41%), myelodysplastic syndrome (n=52, 19.2%), myelofibrosis (n=23, 9%), B-cell acute lymphoblastic leukemia (B-ALL) (n=22, 8.1%), non-Hodgkin lymphoma (n=21, 8%), and chronic myeloid leukemia (n=10, 4%). The median follow-up for survivors was 4.2 (range, 1.1-14.4) years. A total of 80 (14.9%) patients died within 100 days with most deaths attributed to NRM (n=61, 76%). Specific causes of death included infection/sepsis in 22 (27.5%) patients, GVHD in 10 (12.5%), respiratory failure in 9 (11.2%), multiorgan failure in 5 (6.3%), graft failure in 5 (6.3%), and other causes in 10 (12.5%). Progressive disease was the cause of death in 19 (23.8%) patients. Male gender (HR=1.92; p= 0.006), remission status other than CR1 or CR2 for acute leukemia patients (HR=8.44; p<0.0001), non- PTCy strategies (HR=2.4; p= 0.0006), and earlier year of transplantation (HR=1.12; p=< 0.001) were associated with increased risk of mortality at 100 days on univariate analysis. Only use of TBI (HR=2.56, p=0.048) and earlier year of transplantation (HR=1.2; p=0.001) were associated with increased risk of DRM at 100 days post-allografting on univariate analysis. Pertaining to risk of NRM at 100 days, male gender (HR=1.89; p=0.02), diagnosis other than acute leukemia (HR=2.27; p=0.004), non-PTCy strategies (HR=2.44; p=0.003), and earlier year of transplantation (HR=1.1; p=0.004) were adversely associated with NRM. On multivariate analysis, only earlier year of transplantation was found to be associated with increased risk of DRM at 100 days (HR 1.15; p=0.049). Male gender (HR=1.78; p=0.035), diagnosis other than acute leukemia (HR=2.38; p=0.003), and non-PTCy strategies (HR=2.2; p=0.032), were associated with increased risk of NRM at 100 days. Conclusion Non-relapse mortality (NRM) accounted for most deaths within the first 100 days of allo-HCT, primarily due to infection/sepsis and GVHD. Factors associated with increased NRM included male gender and diagnoses other than acute leukemia. Significantly, post-transplantation cyclophosphamide (PTCy) was the only treatment strategy modification that decreased 100-day NRM and improved survival, independent of the transplantation year.

Abstract Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. In a multivariable analysis, receipt of ≥3 lines of therapy before tisa-cel (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.13-3.08; P = .015), any-grade cytokine release syndrome (HR, 1.78; 95% CI, 1.17-2.71; P = .007), and lack of neutrophil recovery (HR, 2.63; 95% CI, 1.47-4.69; P = .001) were associated with an increased risk for any infection. Similar associations were observed for bacterial infections, with the addition of younger age as an adverse risk (<6 vs 6-15 years; HR, 2.38; 95% CI, 1.23-4.61; P = .01). Risk factors for viral infections included increasing age (1-year increase; HR, 1.05; 95% CI, 1.01-1.09; P = .016), prior history of any infection (HR, 2.76, 95% CI, 1.40-5.46; P = .004), and prior hematopoietic cell transplant (HR, 2.10; 95% CI, 1.18-3.71; P = .011). D100 infection-related mortality (IRM) rate was low at 0.2% (95% CI, 0.0-0.8). In this multicenter real-world study, we observed a high incidence of infectious complications but a low IRM following tisa-cel for R/R B-ALL.

Abstract Allogeneic stem cell transplant (ASCT) remains the only curative option in chronic myelomonocytic leukemia (CMML). We retrospectively analyzed 138 CMML patients who underwent ASCT at the Mayo Clinic. Patients who transitioned to ASCT while in chronic phase (Group A) displayed superior post-transplant survival (PTS), compared to those in whom ASCT was performed after blast transformation (BT; Group B) (median 95 vs. 16 months; p=0.01). In Group A, PTS was superior in patients with <5% bone marrow (BM) blasts at time of ASCT (median 164 vs. 13.5 months; p=0.01). Other predictors of superior PTS included day-100 BM blast <5% or normal cytogenetics (median 164 vs 18 months; p=0.01) or presence of chronic graft-versus-host-disease (GVHD; median 164 vs. 26 months; p=0.01). Pre-ASCT hypomethylating agent exposure (HR=2.03; p=0.03), and receiving more than one line of pre-ASCT chemotherapy (p=0.01) predicted inferior PTS. In multivariable analysis, predictors of superior GVHD-free and relapse-free survival (GRFS) included the use myeloablative conditioning and the absence of morphologically or cytogenetically apparent disease at day-100. The use of post-transplant cyclophosphamide (PTCy) was associated with higher cumulative incidence of relapse (p=0.02) and numerically inferior PTS (p=0.1). Group B patients also appeared to benefit from achieving BM blast <5% at time of ASCT (p=0.4) as well as at day-100 (p=0.01), in terms of PTS, while full chimerism and normal cytogenetics at day-100 were associated with superior GRFS. These observations support the value of ASCT in CMML, especially if performed prior to BT and in the presence of <5% BM blasts at time of ASCT. Additionally, the observed detrimental impact of PTCy requires additional studies to confirm and investigate the underlying mechanisms.

LBA1551 Background: Traditional cancer therapy is primarily delivered in clinical settings, imposing logistical, emotional, and financial burdens, particularly on rural and underserved patients. While international studies have demonstrated the safety of home-based chemotherapy, no randomized U.S. trials have evaluated this approach. Mayo Clinic’s CCBW program aims to expand access to high-quality cancer care by providing in-home cancer treatment, lab testing, telemedicine, remote patient monitoring, command center and paramedic support. This pragmatic randomized controlled trial evaluates feasibility and impact of home-based versus in-clinic cancer directed therapy on patient preference, acceptability, safety, and patient-reported outcomes. Methods: Adult patients (ECOG 0-2) receiving chemotherapy or hormonal therapy at Mayo Clinic Florida were randomized 1:1 after confirmation of treatment tolerance in clinic to receive (1) home-based care for 24 weeks or (2) in-clinic care for 8 weeks followed by home-based care for 16 weeks. Target accrual is 200 patients. A planned interim analysis after 50 enrollments assessed accrual, data completeness, technical challenges, safety, and study outcomes. The primary endpoint is patient ratings of their overall cancer care experience (0–10 scale, CAHPS Cancer Care Survey) at 8 weeks. 200 patients provide 80% power to detect a 0.45 standard deviation difference in mean ratings between arms with a 2-sided 2-sample t-test (α=0.05) and 20% missing data rate. Secondary endpoints are patient preference, comfort with home infusions, treatment worthwhileness, functional/symptom assessments (EORTC QLQ-F17, PRO-CTCAE, GP5), grade ≥3 AEs, hospitalizations, and overall survival. Cost is a tertiary endpoint. The trial is IRB-approved (#23001719) and registered (NCT05969860). Results: Enrollment began 8/23/23. As of 2/21/25, 52 patients (26 per arm) were enrolled and 36 started protocol treatment. Common cancers were breast (38%), colorectal (21%), prostate (19%), and multiple myeloma (14%). 64% (28/44) of patients were female; 84% identified as White, 14% as Black, and 2% as multiple races. Median distance to clinic was 20 miles (range 2-66). After 8 weeks, patients in both arms rated their overall cancer care experience highly (mean [SD]=9.69 [0.85] versus 9.54 [0.66] for home-based vs. in-clinic care, n=26). After 24 weeks, 73% preferred home-based care, 18% had no preference, and 9% preferred in-clinic care; 100% felt comfortable with home infusions. No grade ≥3 AEs related to location of care have occurred. Conclusions: Early findings support the feasibility, safety, and high patient acceptability of home-based cancer therapy. No safety concerns related to care location were observed and most patients preferred home-based treatment. Ongoing accrual and analysis will assess clinical outcomes and cost implications. Clinical trial information: NCT05969860 .

e23020 Background: Precision medicine studies must overcome the challenges of identifying patients with uncommon molecular targets and small cohort sizes for correlative studies. BASECAMP-1 (NCT04981119) is a prescreening study that uses a single assay to address both problems by: 1) efficiently screening potentially eligible patients for subsequent clinical trials of Tmod logic-gated chimeric antigen receptor T-cell (CAR T) therapies; and 2) providing a large dataset available for translational studies. Methods: Initially, patients were identified for BASECAMP-1 by consenting and genotyping all potentially eligible patients for human leukocyte antigen (HLA)-A*02 heterozygosity. To improve screening efficiency, we co-developed a patient-matching program with Tempus AI, Inc (Tempus), in which Tempus informs the principal investigators of next-generation sequenced (NGS) patients with HLA-A*02 heterozygosity within their health system who may be eligible for BASECAMP-1. Patients are screened using the Tempus xT platform, which uses genomic and RNA sequencing (RNAseq) analyses to determine gene mutations and expression. Enrolled patients with colorectal (CRC), non-small cell lung, ovarian (OVCA), and pancreatic cancers (PANC) were analyzed for tumor purity, mutation distribution, HLA-A*02 loss of heterozygosity (LOH) status, and RNAseq to validate the data available for future clinical analyses. Results: As of January 3, 2025, 80 participants have been enrolled in BASECAMP-1. Through individual screening methods, 1684 patients were screened at 13 study sites, of which 30 patients had tumor-specific HLA-A*02 LOH and were enrolled (~1 eligible patient identified per 56 screened). The patient-matching program identified 282 patients with HLA-A*02 LOH at 12 sites; of these, 50 consented to the BASECAMP-1 study (~1 patient enrolled per 6 identified), demonstrating higher efficiency than the individual patient screening method. Correlative data from xT were available for 360 patients with germline HLA-A*02 and provided insights into mutational distribution and target expression. LOH status was not associated with tumor-specific differences in missense mutational distribution. RNAseq data demonstrated higher CEACAM5 expression in CRC and higher MSLN in PANC and OVCA vs other tumor types, while EGFR was consistently expressed with reduced variance across tumor types, confirming these as potential target antigens for Tmod CAR T interventional trials EVEREST-1, EVEREST-2, and DENALI-1. Conclusions: Identification and enrollment of HLA-A*02 LOH patients into BASECAMP-1 for logic-gated CAR T therapeutic studies were accelerated by the patient matching program. Concurrent xT analysis provides opportunities to augment analyses from robust propensity-matched comparisons, response correlation studies, and other translational discovery. Clinical trial information: NCT04981119 .