Murthy, Hemant S.

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 .

Abstract Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.

e18508 Background: BPDCN is a rare and aggressive hematologic malignancy. Despite the advent of targeted therapies, median overall survival (mOS) remains <1 year (y) in the absence of stem cell transplant (SCT). This study evaluates clinical and molecular predictors of outcomes in a large cohort of BPDCN patients at a tertiary center. Methods: BPDCN patients seen at Mayo Clinic (AZ, FL, MN) between 2000-2024 were identified retrospectively. Analyses considered parameters at diagnosis. Next generation sequencing (NGS) was performed using a 47-gene assay. Standard statistical methods were used; calculations used R. Results: Among 69 patients, the median age was 70y (range 19-94) with male predominance (83%). At presentation, skin (80%), bone marrow (73%), lymph nodes (52%), spleen (27%), and CNS (12%) were involved; 26% had a concurrent hematologic malignancy. Among 20 cases with NGS, the median number of mutations was 3 (range 0-5), most frequently TET2 (n=16), ASXL1 (n=13), SRSF2 (n=7), and NRAS (n=5). Frontline therapy (Table) yielded a complete response (CR) rate of 63% and overall response rate of 76%. CR rates were similar among regimens, but patients who received an ALL (hyper-CVAD based) regimen (8/13) or tagraxofusp (6/9) were more likely to be bridged to SCT (6/29, p<0.01). After median follow up of 38 months (mo), mOS for all was 15 (95% CI 12-21) mo; 44 (64%) were deceased at last follow up. Among 62 evaluable patients, 20 (32%, median age 60 vs 74y, p<0.01) underwent SCT which improved survival (mOS 51 vs 10 mo, 3y OS 52% vs 5%, p<0.01); mOS was not different between allogeneic (n=17) and autologous (n=3) SCT (54 vs 38 mo, p=0.45). When censored for SCT, the 1y OS for patients receiving an ALL regimen, tagraxofusp, or other regimen was 82%, 67%, and 47%, respectively (p=0.15). In univariate analysis, age ≥50y, lymph node involvement, bone marrow involvement, hemoglobin <10 g/dL, leukocytes (WBC) >11 x10 9 /L, abnormal karyotype, and HCT were significantly associated with OS. In multivariate analysis, WBC >11 x10 9 /L (HR 3.7, p<0.03), abnormal karyotype (HR 5.4, p<0.01), and SCT (HR 0.23, p<0.01) remained significant. Separately, SRSF2 mutation was associated with inferior OS (15 vs 51 mo, p=0.02), but significance was lost when adjusted for age, abnormal karyotype, and SCT. Conclusions: Newly-diagnosed BPDCN patients treated with an ALL regimen or tagraxofusp followed by SCT had longer OS compared to those treated with all other regimens. WBC >11 x10 9 /L and abnormal karyotype were independent predictors of inferior survival whereas SCT was beneficial. Regimen N Age (y) ANNOVA CR Chi Sq HCT Chi Sq 1y OS mOS (mo) Log-rank Tagraxofusp 9 68 (40-70) <0.001 7 (78%) 0.548 6 (67%) 0.018 88% 20.8 0.121 ALL 13 43 (20-72) 8 (67%) 8 (62%) 74% 50.7 Hyper-CVAD 11 43 (20-72) 6 (60%) 6 (60%) 67% 35.8 AML 18 70 (48-80) 13 (76%) 5 (28%) 58% 14.2 Intensive 8 66 (48-77) 7 (88%) 3 (38%) 57% 12.4 HMA+Venetoclax 8 69 (65-80) 6 (75%) 2 (25%) 50% 14.0 Lymphoma 8 74 (49-85) 3 (43%) 1 (13%) 50% 14.0 CHOP 6 74 (49-85) 3 (50%) 1 (17%) 50% 17.7 Other 3 66 (63-73) 1 (33%) 0 (0%) 33% 12.0