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Abstract Background: Intravenous (IV) isatuximab plus pomalidomide and dexamethasone (Isa-Pd) is approved for treatment in patients with relapsed/refractory multiple myeloma (RRMM) based on the ICARIA-MM study. Subcutaneous (SC) administration of Isa offers potential advantages such as shorter administration duration and greater patient comfort compared with IV routes. Isa SC via an on-body injector (OBI), an investigational wearable bolus injector, demonstrated safety and efficacy in a Phase 1b study in patients with RRMM. The IRAKLIA trial (NCT05405166) was the first Phase 3 trial evaluating the non-inferiority of Isa-Pd SC via an OBI vs Isa-Pd IV in patients with RRMM. Here, we report the findings of the IRAKLIA trial in the East Asian subgroup with RRMM. Methods: This global, multicenter, open-label study enrolledpatients aged ≥18 years with RRMM who had received ≥1 prior line of therapy (LOT) including lenalidomide and a proteasome inhibitor (PI). Patients were randomized 1:1 to Isa SC (1400 mg) or Isa IV (10 mg/kg) weekly in Cycle (C)1, then every 2 weeks in addition to P (4 mg orally daily, Day [D]1-21) and d (40 mg orally [20 mg if age ≥75 years] weekly). Treatment was administered in 4-week cycles and continued until disease progression, unacceptable toxicity, or patient withdrawal. Co-primary endpoints included overall response rate (ORR) and observed Isa concentration before dosing (Ctrough) at steady state (predose at C6D1). Key secondary endpoints included rate of very good partial response or better (≥VGPR), Ctroughlevel Cycle 2 Day 1 (C2D1), infusion reaction incidence, and patient satisfaction rate based on the patient experience and satisfaction questionnaire (PESQ) at C5D15. Results: The East Asian subgroup consisted of 105 patients from China (Mainland, n=82 and Taiwan, n=1) and Japan(n=22) (SC, n=50; IV, n=55). Baseline characteristics of the East Asian subgroup were generally balanced between the two arms and generally comparable to the overall global population (median age 62 years; median 2 prior LOT; 29.5% high-risk cytogenetics; 82.9% refractory to lenalidomide; 7.6% prior exposure to daratumumab). After a median of 13.0 months follow-up, ORR in the SC and IV arm was 74.0% and 70.9%, respectively (relative risk [95% CI] = 1.044 [0.815 – 1.335]). The mean (SD) of Ctroughat C6D1 was 502 (232) µg/mL for SC arm and 282 (123) µg/mL for IV arm. The geometric mean ratio (90% CI) comparing SC to IV for Ctrough at steady state was 1.756 (1.346 – 2.290). The ≥VGPR rates were 58.0% for SC and 50.9% for IV (relative risk [95% CI] = 1.139 [0.798 – 1.631]). The mean(SD) of C2D1 Ctroughlevel was 420 (161) µg/mL for the SC arm and 262 (111) µg/mL for IV arm. The geometric mean ratio (90% CI) comparing SC to IV for Ctrough at C2D1 was 1.673 (1.321 to 2.120). The infusion reaction incidence was 0% and 21.8% for SC and IV, respectively. Grade ≥3treatment-emergent adverse events were observed in 82.0% and 87.3% of patients in the SC and IV arms, respectively. Treatment discontinuation rates were 6% for the SC arm and 12.7% for the IV arm. Injection site reactions (ISRs) occurred in 4% (2/50) of patients in the SC arm and in 0.21% (2/964) of SC injections (all Grade 1), with 99.3% of SC injections completed successfully. Isa SC patients expressed higher satisfaction with their injection method, with 64.0% of patients reporting “satisfied” or “very satisfied” vs 52.7% of Isa IV patients (odds ratio [95% CI] = 1.594 [0.728 – 3.489]). Conclusions: The efficacy, safety and pharmacokinetic results between Isa SC vs IV + Pd in the East Asian population from the IRAKLIA study were consistent with the results of the overall global population, in which non-inferiority of ORR, Ctrough at C6D1, ≥VGPR and Ctrough at C2D1 was demonstrated and statistically significantly fewer infusion reactions and higher patient satisfaction were also noted for SC vs IV. These results support the potential use of Isa SC delivered via OBI in East Asian patients and demonstrate the potential of this delivery method to improve patient experience and practice efficiency.

Abstract Introduction: The CAR-T therapies ide-cel and cilta-cel are approved for patients (pts) with relapsed/refractory multiple myeloma (RRMM). The aim of this study was to determine the incidence, subtypes, and associated risk factors for subsequent primary malignancies (SPMs) in MM pts treated with CAR-T therapy in the real-world setting. Methods: A retrospective, multicenter observational cohort study was conducted of pts who received CAR-T therapy between May 2021 and Dec 2024 at 15 centers within the US Multiple Myeloma Immunotherapy Consortium. Logistic models were used for univariable analyses of invasive SPMs (excluding non-melanoma skin cancers). Variables significant at p < 0.10 were included as candidate variables in the multivariable analysis. Time to event endpoints were analyzed using Kaplan-Meier curves. Results: Of n=1460 CAR-T recipients, median follow-up from the time of CAR-T infusion for the entire cohort, ide-cel, and cilta-cel pts was 13.1, 16.9, and 10 months, respectively. A total of 55 invasive SPMs were noted in 53 pts (SPM incidence 3.6%). The incidence rate of SPMs was 4.55 per 1,000 person-years, based on 53 SPMs occurring over 11,646.14 person-years (calculated from CAR-T to the SPM diagnosis, death, or last follow-up). Baseline characteristics were similar for pts with no SPM versus SPM including: age at CAR-T (median 67 vs 65), female (36% vs 43%), Black (13% vs 16%), prior autologous transplant (87% vs 80%), lenalidomide for ≥2 years (31% vs 27%), high risk cytogenetics (23% vs 29%), and known clonal hematopoiesis (7.5% vs 9.9%). Differences were observed in baseline characteristics among pts with SPM versus no SPM for ≥2 prior alkylator lines of therapy (LOT) (82% vs 60%, p=0.002) and median prior LOT (6 vs 5, p=0.008). There was a trend for more patients with SPMs being age ≥70 (35% vs 37%, p=0.074). Of the 53 SPMs, 26 (49%) were myeloid (MDS or AML), 19 (35.8%) were solid, 7 (13.2%) were of T-cell origin, and 1 was a B-cell lymphoma. Of the T-cell SPMs, three were of T-LGL, though one of the T-LGL pts later developed an invasive CNS T-cell lymphoma (CAR-negative). There were four cases of confirmed CAR-positive T-cell SPMs (all pts treated with cilta-cel), of which two were indolent T-cell lymphoma of the GI tract and two were cutaneous PTCL. There was no difference in total incidence of SPMs among pts who received ide-cel (total=4.4%; myeloid=2.2%, T-cell=0.04%) versus cilta-cel (total=3%; myeloid=1.4%; T-cell=0.5%) (p=0.21). Median OS from the time of CAR-T therapy was 40.8 months for pts without SPM compared to 27.6 months for pts with SPM (p=0.4). Median OS did not differ by myeloid, solid, and T-cell subgroup: 26.4, 37.2, and 24 months, respectively (p=0.21). Median time from CAR-T cell to SPM was 12 months overall, and by subtypes of myeloid, solid, and T-cell was 13.2, 9.6, and 9.6 months, respectively (p=0.74). There was no difference in time to any SPM among pts receiving ide-cel versus cilta-cel (p=0.61). An earlier time to diagnosis of myeloid SPM was observed for cilta-cel versus ide-cel (4.8 vs 20.4 months; p=0.003). Median OS from the time of diagnosis of any SPM, myeloid, solid, or T-cell SPM was 9.6, 7.2, 15.6, and not reached in months, respectively (p=0.006), demonstrating that pts diagnosed with myeloid subtype SPM had inferior OS from the time of their SPM diagnosis compared to other subtypes. The cause of death of 4/11 myeloid SPM pts was the myeloid SPM itself. In univariable analysis for the entire cohort, age ≥70 (p=0.079), ≥5 prior LOT (p=0.012), and ≥2 prior alkylator LOT (p<0.001) were associated with higher risk for SPM. In multivariable analysis, ≥2 LOT containing alkylators was associated with higher risk of SPM (p=0.005). For the univariable analysis of the myeloid subgroup, ≥2 prior alkylator LOT (p=0.016) and ≥2 years of lenalidomide maintenance (p=0.063) were associated with higher risk of SPM. In multivariable analysis, ≥2 years of lenalidomide (p=0.065) was associated with a trend toward increased risk of myeloid SPM. Conclusions: With a median follow up of 13.1 months, the incidence of developing a SPM following CAR-T in pts with RRMM was 3.6%, of which approximately half were myeloid malignancies. There was no difference in SPM incidence when comparing the two CAR-T products. Pts treated with ≥2 alkylator LOT had a higher risk of SPM in multivariable analysis and may warrant additional monitoring for SPM development.

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: The landscape of classical hematology has undergone substantial evolution over the last decade, marked by new diagnostic tools, nuanced therapeutic strategies, and an expanding understanding of underlying pathophysiology. This increasing complexity often presents unique diagnostic and therapeutic challenges. These challenges are further compounded by workforce shortages in classical hematology marked by educational gaps, geographic limitations, and difficulty accessing prompt specialty care. Unlike the well-established “Tumor Boards” in oncology, a comparable dedicated, widely accessible forum for classical hematology has largely been absent. This gap contributes to potential practice heterogeneity and isolation, especially across dissimilar care settings and geographic regions, impacting the consistent application of evidence-based practices and access to specialized expertise. To address this critical need, the “Blood Board” initiative was created to serve as an informal, virtual resource for discussing classical hematology topics and cases, fostering diverse perspectives, and collaborative problem-solving. Methods: The Blood Board was formally launched in April 2025, operating as a bi-monthly, hour-long virtual meeting conducted via non-recorded videoconferencing. The forum was designed with broad inclusivity in mind, welcoming all healthcare professionals involved in the care of adult patients with classical hematologic disorders, including trainees such as hematology/oncology fellows, academic and community-based hematologists, and any other interested providers. To date, dissemination of this initiative has been by word of mouth and e-mails containing a calendar invitation have been sent to anyone interested in participating (https://forms.gle/doyHNSx1SVFBJZmy8). To facilitate participation from various practice models and geographical locations, the virtual format was prioritized, eliminating barriers of travel and time commitment often associated with traditional in-person conferences. Participation is voluntary, encouraging an open and informal environment for de-identified case presentations, didactic discussions, and expert opinion sharing. Self-reported data on participant demographics (e.g., role, practice setting) and geographical representation have been collected to assess the initiative's reach and impact. Results: To date, sessions have consistently garnered engagement with a median of five participants in attendance at each session. There have been over 20 unique participants representing a broad spectrum of roles including both trainees and practicing hematologists/hematologist-oncologists and drawing from private practice, community-based hospitals, and academic medical centers. Over half of all participants were either in fellowship or within five years of completion of training. The virtual format has successfully overcome geographical limitations, attracting attendees from numerous states including Alabama, Florida, Georgia, Maryland, Minnesota, Missouri, Pennsylvania, South Dakota, and Wisconsin highlighting its broad appeal and potential for knowledge dissemination across a wide professional network. Conclusions: The Blood Board has demonstrated utility and met a previously unaddressed need. Sustained intellectual interest in Blood Board, coupled with a wide geographical and professional reach underscores a critical role for accessible, free, and multidisciplinary collaborative platforms in the evolving field of classical hematology. Similar to Tumor Boards, Blood Board promotes knowledge exchange and evidence-based care, garners expert support for challenging cases, and harmonizes clinical approaches, which we hope may ultimately improve patient care outcomes across diverse settings. Furthermore, this platform facilitates a national classical hematology community to support workforce development. Future goals include expanding dissemination efforts, measuring specific educational benefits, analyzing impacts on patient care, and increasing participant diversity, including recruitment of advanced practice providers and pharmacists.

Abstract Zieve's syndrome is a rare and often overlooked complication of alcohol misuse, likely under-recognized due to limited physician awareness. We present a unique case with an atypical and misleading clinical presentation that initially raised concern for a hepatic mass. Despite the diagnostic uncertainty, the astute clinical vigilance and thoughtful evaluation by the treating team led to the correct diagnosis of Zieve's syndrome. This case highlights the importance of maintaining a broad differential and considering alcohol-related syndromes even when initial findings suggest alternative etiologies. We present the case of a 29-year-old man with a history of essential tremor managed on propranolol, who was transferred for further evaluation of worsening jaundice following a brief, self-resolving viral-like illness. He denied abdominal pain, ongoing gastrointestinal symptoms, intravenous drug use, or alcohol intake. Initial CT abdomen/pelvis showed hepatic steatosis and a 4.5 × 2.5 × 7.0 cm lobulated hypodense lesion in the right hepatic lobe, raising concern for pyogenic abscess versus neoplasm. Gallbladder wall was mildly thickened (5 mm) without pericholecystic fluid or biliary dilation. He was transferred for further evaluation. Laboratory evaluation revealed macrocytic anemia (Hb 9.9 g/dL, MCV 102 fL), thrombocytopenia (PLT 148), markedly elevated bilirubin (total 12.9 mg/dL, direct 6.8 mg/dL), transaminitis (ALT 93 U/L, AST 217 U/L), and evidence of hemolysis with low haptoglobin (30 mg/dL), elevated LDH (339 U/L), and a low reticulocyte count (0.39%). Sodium was 127 mmol/L, and INR was normal. Hepatitis viral panel, urine drug screen, and urinalysis were negative. Lipid panel revealed extreme hyperlipidemia with triglycerides 1500 mg/dL, LDL 687 mg/dL, and total cholesterol 1300 mg/dL. Peripheral smear showed macrocytic anemia with mild anisocytosis, slight polychromasia, and mild red blood cell agglutination. RUQ ultrasound showed hepatic steatosis with no focal lesion. MRI liver protocol revealed hepatomegaly and diffuse hepatic steatosis with sparing in the falciform ligament, gallbladder fossa, and portions of the right hepatic lobe explaining the CT “lesion” as focal fat sparing rather than a true mass. Although the patient denied alcohol misuse, phosphatidylethanol (PEth) testing was positive, confirming recent heavy alcohol consumption. The clinical picture was consistent with alcohol-associated liver injury, hemolysis, and secondary hyperlipidemia. In conclusion, Zieve's syndrome is characterized by a triad of hemolytic anemia, cholestatic jaundice, and transient hyperlipidemia. Prompt recognition of this underdiagnosed condition is crucial, as it can prevent unnecessary invasive interventions and shift the clinical focus toward supportive care and alcohol cessation, which remains the cornerstone of treatment.

Abstract Background: Philadelphia chromosome–negative (Ph–) ALL is a genetically heterogeneous entity defined by recurrent cytogenetic and molecular aberrations that shape its clinical trajectory and prognosis. Historically poor outcomes in adults prompted significant changes in therapeutic approaches over the past decade, resulting in improved survival. Currently, blinatumomab is a bispecific T-cell engager targeting CD19 in leukemic cells and CD3 on T Lymphocytes. It has shown significant results in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, its role in the frontline treatment of Philadelphia chromosome–negative (Ph–) B-ALL, particularly in combination with chemotherapy, is continuously being explored. Objective: Our purpose is to evaluate the efficacy of blinatumomab-based frontline regimens in adolescents and adults with newly diagnosed Ph– B-ALL through a systematic review and meta-analysis of proportions. Methods: We systematically searched PubMed, Embase, and Cochrane from inception through May 2025. Eligible studies included adolescents or adults with a cut off age of 15 years old, with newly diagnosed Ph– B-ALL where blinatumomab was used in the induction phase, consolidation phase, or both. Primary outcomes were complete remission (CR), measurable residual disease (MRD) negativity, and 3-year overall survival (OS). Random-effects proportional meta-analyses were conducted using logit or Freeman–Tukey transformations. Risk of bias was assessed using RoB 2 for Randomized Controlled Trials and ROBINS-I for prospective trials. Subgroup analysis was performed, dividing subgroups by phase of Blinatumomab utilization; either induction, consolidation or both. To tackle heterogeneity in the MRD pooled results, we conducted a Meta-regression to evaluate the link between different treatment phases and sample sizes. Results: Thirteen studies (n = 878 patients) met the inclusion criteria. The pooled CR rate after induction-phase blinatumomab was 78% (95% CI: 71–85%; I² = 21.2%). The pooled MRD negativity rate was highest in the induction-only group, at 90% (95% CI: 83%–95%), with no significant heterogeneity (I² = 0%). The consolidation group showed a pooled MRD negativity rate of 88% (95% CI: 75%–96%), though heterogeneity was substantial (I² = 74.2%, p = 0.0087). For patients treated during both induction and consolidation, the pooled MRD negativity rate was 89% (95% CI: 82%–94%), also with no observed heterogeneity (I² = 0%). The overall pooled MRD negativity rate across all ten studies was 89% (95% CI: 84%–93%), using a random-effects model with Freeman–Tukey double arcsine transformation. A meta-analysis of four studies reporting 3-year overall survival (OS) following frontline blinatumomab-based therapy was performed, stratified by treatment phase. In the consolidation subgroup, the pooled 3-year OS was 83% (95% CI: 76%–88%), with no heterogeneity (I² = 0%, p = 0.4032). In contrast, for patients treated during both induction and consolidation, the pooled 3-year OS was 52% (95% CI: 22%–81%), with substantial heterogeneity (I² = 88.6%, p < 0.0001). Conclusions: Blinatumomab-based regimens in the frontline setting are associated with high MRD clearance and complete remission rates, particularly when used during induction or consolidation. However, the predominance of non-randomized studies, small sample sizes, and heterogeneity in MRD assessment limit definitive conclusions. Prospective randomized trials are needed to clarify the optimal integration of blinatumomab in frontline Ph– B-ALL therapy.

Abstract Background: Clostridioidesdifficile infection (CDI) represents a significant infectious complication in both Chimeric Antigen Receptor(CAR) T-cell therapy and hematopoietic stem cell transplant (HSCT) recipients. We sought to investigate the incidence and outcomesof CDI among various CAR-T therapy products. Methods: This retrospective study used the 2022 National Inpatient Sample Database to identify and include adult patients with a primary diagnosis of four hematologic malignancies (Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), Acute Lymphoblastic Leukemia (ALL), and Acute Myeloid Leukemia (AML). In this cohort, we isolated patients who developed CDI using ICD-10 codes. Subgroup analysis was performed based on the type of CAR-T cell therapy and HSCT recipients. Multivariate regression analysis was performed to identify independent risk factors for CDI and mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 8,739 patients with CDI were identified among 507,559 patients with four hematologic malignancies, representing an overall incidence of 1.72%. Patients receiving CAR-T cell therapy (5% vs 2%, p<0.05), bone marrow transplant (BMT, 3% vs 2%, p<0.05), and those with a history of BMT (6% vs 2%, p<0.05) were at significantly higher risk for CDI. Among individual CAR-T products, the incidence was: for CD19-directed CAR-T, Brexu-cel 5%, Axi-cel 6%, Tisa-cel 5%, and Liso-cel 3%; for BCMA-directed CAR-T, Ide-cel 4% and Cilta-cel 5%. There was no significant difference in CDI rates between these individual CAR-T products. Among CAR-T recipients by cancer type, CDI incidence was NHL 5%, MM 4%, ALL 7%, and AML 5% (p=0.79). Multivariate regression identified history of HSCT (OR 2.11, 95% CI 1.09–4.08), cytokine release syndrome (OR 1.7; 1.26–2.52), protein-energy malnutrition (OR 2.08; 1.83–2.36), graft versus host disease (OR 2.52; 2.02–3.15), and female sex (OR 1.23; 1.10–1.38) as significant independent risk factors for CDI (all p<0.05). Overall mortality in those with CDI was 6% compared to 5% without, and mortality increased substantially to 36% in those requiring surgical intervention for CDI. Conclusion: In patients with hematologic malignancies, identifying risk factors and rates of CDI in CAR-T cell therapy is essential for prompt recognition and effective management. Future research on optimizing CDI screening protocol and prevention strategies can help reduce mortality and morbidity in this immunocompromised population.

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 Background Accurate reconstruction of electronic health record (EHR) treatment sequences is essential for leveraging real-world data (RWD) in clinical research and trial-eligibility platforms in multiple myeloma (MM). However, inconsistencies in RWD treatment documentation and the complexity of line-of-treatment (LOT) assignments in MM hinder reproducibility and limit comparisons against published trials. To address these limitations, we developed HEAL-MM, an automated rule-based algorithm that systematically parses structured medication data to calculate LOTs and segment treatment into standardized, clinically meaningful phases. The algorithm is designed to be interpretable, adaptable to evolving therapeutic frameworks, and compatible with widely adopted EHR data standards. Here, we report its real-world validation against expert-adjudicated treatment sequences to assess concordance, identify edge-case failure points, and support RWD integration. Methods A stratified cohort of 100 MM patients (9,136 structured treatment events) was curated from 114 unique healthcare systems compiled from the multi-institutional HealthTree Foundation harmonized registry. Cohort selection was randomized to ensure coverage across diagnostic eras (pre-2010, 2015–2020, 2022–2025) and treatment exposures, including CAR T-cell therapies, bispecific antibodies, and anti-CD38-based regimens. HEAL-MM sequenced MM regimens chronologically and applied predefined logic rules to identify LOT transitions, the initiation of a new therapeutic course based on drug changes, treatment gaps, and procedural anchors such as stem cell transplant or CAR T. Within each LOT, the algorithm segments and labels therapy into phases, clinically distinct intervals (e.g., induction and maintenance) using rule-based clinical logic. Outputs were benchmarked against expert-labeled adjudications. Concordance was evaluated using concordance index (C-index), stratified by patient, LOT depth and diagnostic era. Results: HEAL-MM demonstrated high concordance with expert-labeled treatment sequences: 0.94 for LOT identification, 0.98 for treatment phase segmentation, and 0.96 for phase label assignment. Achieving complete agreement with all expert annotations in 90% of patients for LOT assignment, 94% for the number of treatment phases identified, 77% for the specific labels applied to each phase, and 75% across all three dimensions simultaneously. Among discordant patients, the absolute difference in final LOT count was 0.5 ± 0.9. Performance was highest in early lines (LOTs 1–3; C-index: 0.97), with seven patients showing discrepancies at this stage. Concordance declined in later lines (LOT ≥4; C-index: 0.87), where 50% of the discordant cases (n=4) were attributable to misclassifications in earlier LOTs, such as medication restarts following >3-month gaps, demonstrating the compounding effect of early errors on longitudinal accuracy. Temporal stratification revealed improved accuracy in post-2020 cases (C-index: 0.94) compared to 2015–2020 cohorts (0.91), reflecting the increasing adoption of structured treatment standards and EHR data quality improvements. To assess HEAL-MM performance at clinically significant junctures, we analyzed treatment transitions that initiated a new LOT or marked a change in phase, achieving C-indices of 0.97 for LOT transitions, 0.97 for treatment phase shifts, and 0.94 for phase label assignment. Conclusions: HEAL-MM provides a validated, scalable solution for standardizing MM treatment structures in RWD environments, as it accurately detects the exact treatment entry of a new LOT 97% of the time. This rule-based framework enables reproducible LOT and phase assignment across heterogeneous EHR systems, supporting real-time cohort identification across institutions and EHR platforms. The algorithm's modular design allows for continuous integration of novel therapeutic categories and evolving treatment logic. While the algorithm maintained high fidelity overall, early-stage misclassifications consistent with increased heterogeneity and documentation ambiguity occasionally propagated downstream, underscoring the compounding effect of upstream errors in longitudinal reconstruction. With its generalizable structure and compatibility with industry-standard data models, HEAL-MM lays the foundation for structured treatment reconstruction in MM across RWD infrastructure and serves as a transferable blueprint for other hematologic malignancies.

Abstract Background: For LS-DLBCL, clinical trials (FLYER, LYSA/GOELAMS 02-03, LYSA LNH09-1B, S1001) have shown that 4 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP4) without radiation (RT) leads to durable remissions in >90% of cases. However, only patients (pts) with non-bulky disease and/or international prognostic index (IPI) of 0 and complete metabolic response (CMR) on interim positron emission tomography (PET) scan, if performed, were eligible for RCHOP4 alone in these studies. Outcomes in trial-ineligible LS-DLBCL and the appropriate real-world candidates for RCHOP4 are still undefined. Methods: We conducted a multicenter retrospective study of adult pts with stage I/II DLBCL of any tumor bulk, IPI and with or without B-symptoms diagnosed after 2011 and treated with RCHOP4 +/- 2 cycles R from 21 U.S. centers. Pts with PMBCL, PTLD or receiving non-standard dose RCHOP for cycle (C) 1 or planned consolidative RT were excluded. The primary endpoint was PFS from C1 by Kaplan-Meier method, not counting indolent lymphoma relapse. Event free survival (EFS) was time to next therapy without progression (including unplanned RT for non-CR), progression or death. A competing risks analysis of non-relapse mortality (NRM) vs. DLBCL progression was performed. Results: The characteristics of the 428 pts were: median age 60 (18-88), 60% male, 11% Hispanic and 4% non-Hispanic Black, 62% stage I, 15% elevated LDH, 3% ECOG PS>1, 5% tumor bulk >7cm, 9% had B-symptoms and median Charlson Comorbidity Index (CCI) was 4 (2-12). IPI was 0, 1 and 2-3 in 42%, 46% and 12% and stage-modified IPI (smIPI) was 0, 1, 2 and 3-4 in 25%, 48%, 21% and 6% of pts. 66% had nodal (59% head/neck, 11% pelvic, 9% multiple above diaphragm, 7% abdominal) and 46% extranodal sites (37% head/neck, 20% gastric/intestinal, 9% spleen, 8% skin/soft tissue); 6% had transformed/concurrent FL/MZL or grade 3B FL, 33% (138/408) were non-GCB cell of origin (COO), 25% (90/357) double expressor (DEL) and 0.5% (2/379) double-hit. 13% had completely resected disease, 97% staging PET and 47% bone marrow biopsy. Median diagnosis to treatment interval was 30 days (IQR 20-43), 6% had dose reductions after C1, 77% had an interim PET (iPET) after C2 (33%) or C3 (67%), 15% received 2 additional cycles R and 4% CNS prophylaxis. CMR rates by iPET were 83% after C2 and 94% after C3, and 95% by end-of-treatment PET. iPET PMR was more likely if smIPI>2 or bulky disease. Median follow-up time was 2.7 years. There were 32 progression events: 14 occurred at the primary site and 17 at distant sites (1 unknown), and 12 occurred after 2 years. Another 11 pts received unplanned RT after RCHOP4 for non-CR. There were 24 deaths, 12 without prior progression. Cause of death was DLBCL in 7 and non-DLBCL in 17 cases (6 infection, 2 ILD, 2 heart failure, 2 second cancer, 1 seizure, 4 unknown). EFS, PFS and OS rates were 88%, 90% and 96% at 3 years. By univariable Cox regression, Black race, elevated LDH, smIPI>2, DEL, increasing CCI, multiple subdiaphragmatic nodal sites and iPET PMR were associated with worse PFS. Non-significant variables of note included COO, extranodal sites, complete resection, missing bone marrow biopsy, missing iPET and additional cycles R. By multivariable analysis (including age>60, stage, ECOG PS>1, elevated LDH, bulky disease, CCI, B-symptoms and DEL), ECOG PS>1 (HR 3.95 p=0.050), CCI (HR 1.29 p=0.003) and DEL (HR 2.02 p=0.069) were associated with worse PFS. Cumulative incidence of DLBCL progression and NRM were 8% and 2% at 3 years. Competing risk analysis by univariable models found that age>60, ECOG PS>1, smIPI>2, elevated LDH, CCI and bulky disease were associated with NRM, while DEL and B-symptoms were associated with DLBCL progression.Conclusion: Presented is the largest retrospective cohort of LS-DLBCL treated uniformly with RCHOP4 to date. Despite modest follow-up time and lack of an “intention-to-treat“ population, this study shows that abbreviated RCHOP4 leads to excellent outcomes in the real-world, albeit with continuous risk of late relapse. smIPI risk factors were associated with worse PFS, though this may in part be driven by risk of non-lymphoma death. As pts with advanced age, poor performance status or comorbidities may benefit from reduced treatment exposure, RCHOP4 should still be considered for these and other “trial-ineligible” pts, particularly if other high-risk features (iPET PMR, DEL or B-symptoms) are absent.