Khurana, Arushi

Abstract Introduction: Primary central nervous system T-cell lymphoma (PCNSTL) is a rare form of PCNSL, comprising 2–8% of cases. Prognostic factors remain undefined, and no standard treatment protocol currently exists. Prior studies have been limited by small sample sizes, incomplete molecular profiling, and poor representation of novel treatment modalities. In this study, we aimed to identify clinicopathologic factors associated with patient (pt) outcomes and delineate the spectrum of treatment regimens used to inform future clinical practice. Methods A multicenter retrospective study was conducted across 15 North American academic institutions. Pts aged ≥18 years with biopsy-confirmed PCNSTL between 2009 and 2025 with no evidence of systemic disease were included. Cases with CNS relapse of systemic T-cell lymphoma were excluded. Baseline characteristics were analyzed using independent t-tests, Fisher's exact tests, or Pearson's chi-square tests. Primary endpoints were overall survival (OS) and progression-free survival (PFS), evaluated by Kaplan–Meier, log-rank tests, and Cox regression. Results: Forty-two pts met inclusion criteria. Median age was 57 (range 19–77), 69% were male, and 79% were white. Most (69%) had ECOG 0–1. No patients had HIV, hepatitis B or C, or a history of solid organ transplant. LDH was elevated at diagnosis in 38%, and 24% had B-symptoms. Mean absolute lymphocyte count at diagnosis was 1.82/µL. The most common histologic subtypes were PTCL-NOS (76%), followed by ALK-negative ALCL (12%) and γδ T-cell lymphoma (5%). All patients had parenchymal brain lesions with 57% having multifocal disease. Additionally, CSF involvement was seen in 21%, vitreoretinal involvement in 3%, and deep brain involvement in 34%. Next-generation sequencing was performed in seven pts (17%), with disease-associated variants identified in three cases. Among these, two pts had mutations in TP53, and one had a mutation in DNMT3A. Cytogenetics were obtained in 7 pts with only one exhibiting a complex karyotype. Only one pt was EBV positive by EBER-ISH. Overall, 79% received HD-MTX-based therapy. First-line treatments were mainly HD-MTX alone (38%), HD-MTX + temozolomide (17%), or vincristine + procarbazine (12%). No patients were treated on clinical trials. Median treatment duration was 78 days and median number of treatment cycles was 4 (range 1–9 cycles). One patient received radiation alone; 5% received radiation with systemic therapy. A steroid pre-phase was used in 60%, with 44% exhibiting a clinical response. Overall response rate to first-line treatment was 63% (13 CR, 12 PR). Imaging alone was used in determining response in all patients. Repeated biopsy was not performed. Twelve patients (29%) underwent consolidative autologous transplant, most commonly with thiotepa/carmustine (TT/BCNU, 69%) or BEAM conditioning (25%). Median duration of follow-up was 10.4 months. Sixty-two percent of pts progressed during the study period, with 7% experiencing extra-CNS relapse. Median PFS was 8.2 months. Improved PFS was associated with >3 cycles of therapy (p=0.03) and transplant with TT/BCNU (p=0.0004). At last follow-up, 43% were in remission and 52% were deceased, mostly due to disease progression (77%). Median OS was 17.6 months. One- and two-year OS rates were 58% and 42%, respectively. OS was associated with Nottingham/Barcelona score <2 (p=0.02), >3 treatment cycles (p=0.0008), response to first-line therapy (p=0.0007), and TT/BCNU-based transplant (p=0.0001). IELSG, Taipei, and MSKCC risk scores were not significantly associated with survival, though IELSG approached significance (p=0.09). Discussion: This study is among the largest cohorts of PCNSTL pts compiled to date. PCNSTL remains rare and heterogenous. Treatment across centers largely mirrors management of B-cell PCNSL with high utilization of HD-MTX regimens and TT/BCNU conditioning autologous transplant. Survival outcomes within our cohort are consistent with those previously reported within the literature. Receipt of >3 cycles of therapy, TT/BCNU conditioning and Nottingham/Barcelona scores were associated with longer survival within our cohort. Limitations of our study include its retrospective design and heterogeneity within pt disease characteristics, treatments utilized and disease assessment intervals. Further exploration into pathophysiology and optimal management of this unique entity is needed.

Abstract Background Chimeric-antigen-receptor (CAR) T-cell therapy has transformed outcomes for relapsed or refractory hematologic malignancies, yet early identification of patients at highest risk for death remains elusive. A prognostic model that leverages only the information routinely available at the time of CAR-T evaluationcould guide pre-infusion counseling, intensity of follow-up, and resource allocation. Methods We analyzed a prospectively maintained cohort of CAR-T recipients treated at Mayo Clinic to develop and test our model. For each patient, data (vital signs, lab results, cardiac assessments [ECG and echocardiography], and PET/CT images) from initial CAR-T evaluation (up to 60 days prior to CAR-T infusion) was considered. Vital signs and labs were left un-imputed, while ECG, echocardiographic parameters, and PET/CT features were forward-filled from the preceding 60 days. Each patient-day was labeled as “outcome present” or “no outcome,” enabling supervised training of gradient-boosting models to predict overall survival (OS) at 6 months post CAR-T infusion. Model performance was evaluated using the area under the ROC curve (AUC) with 10,000-fold bootstrapping with data shuffling between each iteration to derive confidence intervals for stability. To enhance interpretability, we also developed a simplified model using the top 19 features (determined by Shapley value-based importance), aiming to preserve predictive accuracy with a smaller feature set. Results A total of 570 CAR-T cell treated patients were included in this study (476 patients in the training cohort and 94 patients in the validation cohort). The median age was 64 years and 61% males. The primary diagnoses were B-cell lymphoma (324 patients) and multiple myeloma (246 patients). A total of 4,851 individual vital-sign readings, 11,781 laboratory measurements were included. PET/CT images were available in 318 patients. The ML model demonstrated high discriminative ability for predicting OS at 6 months post CAR-T infusion. Vital signs alone produced a mean AUC of 0.63; radiomics features alone produced a mean AUC of 0.71, while laboratory tests alone produced a mean AUC of 0.84. The features most contributory to each single-modality model were then combined into a simplified multimodal model with a total of 19 features, which produced a mean AUC of 0.87, with a 95% CI of 0.73 - 0.97. The 19 features included in the simplified model were: LDH, ferritin, uric acid, eosinophils, fibrinogen, D-dimer, heart rate, mean arterial blood pressure, QTc, QT interval, and the radiomics features of sphericity, first-order Kurtosis, first-order mean, first-order energy, first-order total energy, shape maximum2D diameter (sagittal plane), SUV CoV, SUVp90, shape flatness. This multimodal predictive model was then applied to the validation cohort (uninvolved with model training or testing), which produced an AUC of 0.93, with a 95% CI of 0.84 - 0.98. Conclusions Our ML-driven approach successfully predicts overall survival 6 months post CAR-T infusion, highlighting those individuals at most risk of poor outcomes at the time of CAR-T evaluation. The strong performance of the multimodal version of the model suggests that each data domain contributes complementary resolving power, and by including novel data types, such as PET CT radiomics features, the most accurate predictions could be realized. By providing accurate, near-real-time risk stratification for poor outcomes within 6 months of CAR-T infusion, the model could facilitate proactive patient management. Prospective studies of the integration of this ML model into CAR-T treatment workflows will be crucial to confirm its clinical benefits and to facilitate its adoption in practice.

Abstract Background Neurolymphomatosis (NL) is a rare and frequently underrecognized manifestation of lymphoma, characterized by infiltration of peripheral or cranial nerves by malignant lymphocytes. Limited data exist to guide optimal management. We present the largest single-enterprise (included the 3 Mayo Clinic sites) cohort to date, evaluating disease characteristics, treatment patterns, and outcomes in patients (pts) with NL. Methods We conducted a retrospective analysis of pts ≥18 years (yrs) diagnosed with clinical, radiographic, or biopsy-confirmed NL at Mayo Clinic between January 2002 and December 2024. Baseline characteristics were compared using independent t-tests for continuous variables and Fisher's exact or Pearson's chi-square tests for categorical variables. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR) was a secondary endpoint. Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression were used to assess survival outcomes and associated factors. Results We included 149 pts. Median age at diagnosis was 64 yrs (range 22–83), and 23% were female. Most presented with stage IV disease (89%), and NL was part of the initial lymphoma presentation in 42% (primary NL). Diagnostic confirmation was based on histopathology and imaging in 55%, imaging alone in 26%, histopathology alone in 16%, and clinical features in 4%. Diffuse large B-cell lymphoma was the most common histology (61%), followed by marginal zone lymphoma (7%), and T-cell lymphoma (7%). Clinical presentation included painful neuropathy (65%), concurrent CNS involvement (37%), systemic disease (43%), elevated LDH (46.9%), and ECOG ≥2 (38%). Pattern of involvement included cranial nerves (29%), peripheral nerves (28%), and spinal nerve roots (27%). Median follow-up was 92 months (95% CI, 63–119). Among 137 treatment-evaluable pts, first-line regimens included methotrexate-based (MTX) (62%), bendamustine-based (B) (11%), cytarabine-based (Ara-C) (4%), and rituximab-based (R) (excluding MTX, B, or Ara-C) (15%) therapies. Radiation was used in 18%, and 21% underwent autologous stem cell transplant (ASCT). Among 103 response-evaluable pts, the ORR was 67% (52% complete response [CR], 16% partial response [PR]). ORRs by regimen were 78% (MTX), 92% (B), and 86% (R). On univariate analysis, primary NL (OR 4.3) and frontline ASCT (OR 8.47) were associated with higher odds of response (p<0.05), while ECOG ≥2 (OR 0.24) and localized disease (OR 0.33) were associated with lower odds. On multivariable analysis (MVA), primary NL (OR 5.0 [1.5–12.1], p=0.02) and ECOG >1 (OR 0.2 [0.06–0.79], p=0.018) remained significant predictors of response. Median PFS was 13 months (95% CI, 9–36), with a 2-yr PFS of 43% (95% CI, 35–53). On MVA, concurrent CNS involvement (HR 2.4, p=0.05), systemic disease (HR 2.7, p=0.02), and ECOG >1 (HR 2.4, p=0.02) were associated with inferior PFS, while primary NL was associated with improved PFS (HR 0.3, p=0.002). Patients undergoing frontline ASCT had a median PFS of 108 months (95% CI, 58–not reached) with a 7-yr PFS of 62% (95% CI, 46–84). Among those receiving second line and beyond (2+) therapy, 24 received MTX-based regimens, 10 received CAR-T, and 8 received tyrosine kinase inhibitors. Post-ASCT median PFS was 30 months (95% CI, 15–NR). Among CAR-T recipients, evaluable responses (n=8) included 4 CR, 1 PR, and 3 PD. Median OS was 56 months (95% CI, 29–133), with a 5-yr OS of 50% (95% CI, 41–60). On MVA, ECOG ≥2 (HR 2.5, p=0.02) predicted worse OS, while receipt of ASCT (HR 0.4, p=0.04) and primary NL (HR 0.5, p=0.04) were associated with improved OS. Conclusion This study represents the largest single-enterprise cohort of pts with NL, providing comprehensive insight into its clinical presentation, treatment patterns, and outcomes. Primary NL and preserved PS were independently associated with improved response rates and survival, while CNS and systemic involvement at diagnosis portended poorer PFS. MTX and bendamustine-based regimens achieved high ORR, and frontline ASCT was associated with significantly prolonged remission duration and OS. These findings highlight the prognostic importance of baseline disease burden and functional status, support the early incorporation of high-intensity regimens in eligible patients, and underscore the urgent need for prospective studies to guide evidence-based management in this rare and understudied population.

Abstract Introduction There is currently no standard-of-care for patients (pts) who cannot tolerate full dose anthracycline regimens in frontline large B-cell lymphoma (LBCL). R-miniCHOP is a commonly used regimen that provides curative intent treatment with manageable toxicity. Despite this, lymphoma and treatment-related mortality are the leading causes of death in these pts. Additionally, many pts may not be eligible to receive R-miniCHOP due to comorbidity or frailty. There are limited clinical trial and real-world data focused on this population. Methods Pts with LBCL age 18 years (yrs) and older were identified from the Lymphoma Epidemiology of Outcomes (LEO) cohort, a prospective study of newly diagnosed pts with non-Hodgkin lymphoma enrolled from 2015-2020 at 8 academic medical centers in the US. Pts with LBCL were included in this analysis if they had received R-miniCHOP or a regimen that did not include an anthracycline (nonAC). NonAC regimens included R-CVP, BR, rituximab, radiation and lenalidomide and rituximab. Pts completed the Vulnerable Elders Survey (VES-13) and were considered vulnerable if they had a score >3. Event-free survival (EFS) was defined as the time from start of treatment until progression/relapse, retreatment, or death due to any cause; EFS at 24 months (EFS24) was a secondary endpoint. Overall survival (OS) was defined as the time from start of treatment until death due to any cause. EFS and OS for R-miniCHOP and non-IC groups, as well as vulnerable and not vulnerable by VES-13 were estimated using Cox models. Results A total of 190 pts received R-miniCHOP (N=139) or nonAC (N=51). R-miniCHOP-treated pts were older (median 82 vs 72 yrs) and more commonly female (55% vs 35%). The majority in both groups (86% vs 78%) received their treatment at a LEO center and did not receive therapy on a clinical trial (89% vs 100%). Most pts receiving R-miniCHOP had high-intermediate (32%) or high (30%) international prognostic index (IPI) score, while both high-intermediate (22%) and high (20%) IPI were lower in the nonAC-treated pts. Cell of origin was determined by immunohistochemistry as available clinically, with GCB 42% vs 31%, non-GCB 32% vs 29%, and not done/unknown 26% vs 39% in R-miniCHOP vs nonAC pts. Double-hit status by FISH was known in 115 pts and was positive in 13% of R-miniCHOP pts and 10% of nonAC pts. The diagnosis-to-treatment interval (DTI) was ≤14 days in 30% of R-miniCHOP pts and 24% of nonAC pts. Of pts who had a VES-13 score (N=119), vulnerable status trended higher in the R-miniCHOP (66%) vs the non-IC group (50%; p=0.15). With a median follow-up of 50.5 months, the median EFS was 37.1 months and median OS was 50.0 months. R-miniCHOP, compared with non-IC, was associated with improved EFS (unadjusted HR=0.54, 95% CI 0.36-0.81; p=0.003) and OS (unadjusted HR=0.58, 95% CI 0.38-0.88; p=0.011). When adjusted for age, IPI, LBCL subtype (diffuse large B-cell lymphoma, not otherwise specified vs other), DTI and VES-13, R-miniCHOP was strongly associated with improved EFS (HR=0.26, 95% CI 0.14-0.50; p<0.001) and OS (adjusted HR=0.29, 95% CI 0.15-0.57; p<0.001). EFS24 rate was 56% in all pts and was superior in pts treated with R-miniCHOP vs non-IC (62.7% vs 34.1%; p=0.001). In the R-miniCHOP group, vulnerable status (adjusted for IPI) was associated with inferior OS (HR=2.22, 95% CI 1.09-4.50; p=0.028) and trended towards inferior EFS (HR=1.76, 95% CI 0.93-3.32; p=0.083). In a competing-risk cumulative-incidence analysis, lymphoma was the leading cause of death for pts receiving R-miniCHOP at 2 (0.16, 95% CI 0.11-0.24) and 5 (0.20, 95% CI 0.14-0.28) yrs, as well as for those receiving non-IC at 2 (0.35, 95% CI 0.24-0.53) and 5 (0.38, 95% CI 0.26-0.56) yrs. Treatment-related mortality was similar in both groups. In the R-miniCHOP group, the 2-yr (0.20 vs 0.03) and 5-yr (0.20 vs 0.11) lymphoma-related mortality was higher in pts who were vulnerable vs not by VES-13, while there were no differences for mortality due to therapy or other causes by vulnerable status. Conclusions These data support R-miniCHOP as a curative regimen in older and frail pts with the majority achieving EFS24. R-miniCHOP compared to non-IC use is strongly associated with improved EFS and OS when adjusted for disease and patient related variables. Within the R-miniCHOP group, vulnerable status is associated with inferior OS. Additional research efforts are needed to optimize outcomes for this group of pts.

Abstract Background: De novo secondary central nervous system (CNS) lymphoma (SCNSL), characterized by concurrent systemic and CNS aggressive B-cell lymphoma at diagnosis, is a rare entity with a dismal prognosis. The prognostic significance of the initial anatomical compartment of CNS involvement (parenchymal vs. leptomeningeal) is not well-defined. We sought to analyze outcomes based on CNS localization in a single-institution cohort. Methods We retrospectively reviewed 34 patients with de novo SCNSL (including diffuse large B-cell lymphoma [DLBCL], high-grade B-cell lymphoma, not otherwise specified (HGBCL NOS), and double-/triple-hit lymphoma) treated at the Mayo Clinic between 2002 and 2025. Clinicopathological features, radiologic findings, treatment details, and survival outcomes were abstracted from the medical records. Patients were categorized by the primary site of CNS involvement. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and groups were compared with the log-rank test. Results The study cohort had a median age of 61.5 years (range 19-79) and a median International Prognostic Index score of 3 (range 2-4). Pathological subtypes included double-/triple-hit lymphoma (n=14, 41.2%), non-germinal center B-cell like (non-GCB) DLBCL (n=11, 32.4%), germinal center B-cell like (GCB) DLBCL (n=8, 23.5%), and HGBCL NOS (n=1, 2.9%). Among patients with available data, 14 (43.8%) were positive for MYC rearrangement, 13 (54.2%) for BCL2 rearrangement, and 10 (45.5%) for BCL6 rearrangement. First-line regimens received by patients included MR-CHOP (n=18, 52.9%), DA-R-EPOCH (n=5, 14.7%), combined CODOX-M/IVAC (n=4, 11.7%), R-CHOP with intrathecal methotrexate (n=3, 8.8%), miscellaneous therapies (n=3, 8.8%), and MRT (n=1, 2.9%). The complete response rate was 58.8% (n=20). Intrathecal chemotherapy was administered to 61.8% of patients, and consolidation with autologous stem cell transplant was performed in 35.3%. Based on the CNS compartment involved, de novo SCNSL (DN-SCNSL) were classified into two subtypes: the leptomeningeal subtype, defined as leptomeningeal involvement with or without parenchymal CNS disease (LM-DN-SCNSL; n=22, 64.7%), and the parenchymal subtype, defined as parenchymal-only CNS involvement (P-DN-SCNSL; n=12, 35.3%). Parenchymal disease was multifocal in 75% of cases, supratentorial in 58.3%, and associated with a midline shift in 30%. Although no tested factors (including pathological subtype, age, sex, and bone marrow involvement) were significantly associated with the anatomical compartment, a non-significant trend was noted for BCL6 rearrangement to be more common in the leptomeningeal group (8/13, 61.5%) than the parenchymal group (2/8, 25.0%) (P = 0.18). Survival outcomes were analyzed for both anatomical and pathological classifications. For the parenchymal versus leptomeningeal cohorts, 2- and 5-year Overall Survival (OS) rates were 75.0% vs. 45.1% and 41.0% vs. 38.7%, respectively (P = 0.34). For Progression-Free Survival (PFS), the 2- and 5-year rates were 48.6% vs. 32.5% and 29.2% vs. 26.0%, respectively (P = 0.53). The 2-year OS rates by pathological subtype were 81.8% for non-GCB DLBCL, 45.8% for DHL/THL, and 37.5% for GCB DLBCL (P = 0.27). Survival outcomes (OS/PFS) were not significantly associated with patient age, sex, pathological subtype, or anatomical compartment. Conclusion DN-SCNSL can be anatomically classified into two subtypes: LM-DN-SCNSL and P-DN-SCNSL. While a prognostic trend favoring the parenchymal subtype was observed, the difference did not achieve statistical significance, a finding likely attributable to the small cohort size. This classification may hold clinical utility for guiding risk stratification, and larger studies are needed to validate these findings and identify the most optimal treatments for each subtype of DN-SCNSL.

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare but aggressive non-Hodgkin lymphoma with limited prospective data to guide optimal therapy. This study evaluates real-world treatment patterns and survival outcomes using a large national cohort. Methods We analyzed data from the National Cancer Database (NCDB) for patients diagnosed with PCNSL between 2004 and 2020. Baseline demographics and treatment characteristics were analyzed using descriptive statistics. Survival outcomes were estimated using the Kaplan-Meier method and compared using log-rank tests. Multivariable Cox proportional hazards models were constructed to identify independent predictors of overall survival (OS). Results A total of 14,450 patients with PCNSL were included; 14,439 had first-line treatment data available, and 13,390 had survival data. Median age at diagnosis was 67 years (range 18-90), 49.2% were female, and 6.6% were African American. Chemotherapy alone was the modality of treatment for 81.6% (n=11,787), 12.2% (n=1,769) received chemoradiation, 3.8% (n=545) received chemotherapy and underwent autologous stem cell transplant (ASCT) but no radiation, and 2.4% (n=348) received radiation only. The median follow-up time was 73.5 months (95% CI 71.4-75.6), and the median OS for the group was 17.4 months (95% CI 16.2-18.6). Survival differed significantly by age group (median OS: <65 yrs, 46.1 months [95% CI 41.7 -50.6]; 65-79 yrs, 12.5 months [95% CI 11.2-13.7]; ≥80 yrs, 3.2 months [95% CI 2.9-3.5]; p<0.001), by year of diagnosis (median OS: 2004-2009, 11.0 months [95% CI 9.9-12.1]; 2010-2015, 20.0 months [95% CI 17.4-22.6], 2016-2020, 29.7 months [95% CI 26.0-33.4]; p<0.001), and by frontline treatment strategy (p<0.001). Patients treated with chemotherapy followed by ASCT had the longest median OS (not reached), while those receiving radiation alone had the poorest outcomes with a median OS of 3.9 months (95% CI 3.2-4.7); chemoradiation patients had a median OS of 31.8 months (95% CI 27.5-36.1), and chemotherapy only patients had a median OS of 13.9 months (95% CI 12.7-15.1)(p<0.001). African American patients had an inferior outcome with a median OS of 10.2 months [95% CI 7.2-13.1], compared to “other” races with a median OS of 36.9 months [95% CI 27.6-46.1] (p<0.001), although this is more similar to the median outcome for white patients (17.0 months [95% CI 15.8-18.3]). Treatment at an academic center (25.7 vs 11.0 months) and a high case-volume center (defined as >median number of cases per facility) (18.6 vs 10.5 months), and lower Charlson-Deyo comorbidity scores (CDS) (defined as CDS 0-1) (21.7 vs 6.8 months) were also associated with superior OS (p<0.001). In multivariable analysis, increasing age ( 65-79 y.o HR 1.60 [1.52-1.1.68], ≥80 y.o HR 2.95 [2.75-3.17]), CDS≥2 (HR 1.36 [1.28-1.44]), and African American race (HR 1.12 [1.02-1.24]) were adverse predictors of OS (all p<0.001), while treatment strategy (ASCT [HR 0.17], chemoradiation [HR 0.53], chemotherapy only [HR 0.68] compared to radiation alone), more recent year of diagnosis (2010-2015 [HR 0.81], 2016-2020 [0.70]), and treatment at an academic center [HR 0.81] remained predictors of superior OS (all p<0.001). Conclusion In this large national cohort of patients with PCNSL, treatment with chemotherapy followed by ASCT was associated with the most favorable survival outcomes. Patients treated with chemoradiation or multi-agent chemotherapy also demonstrated improved survival compared to those receiving radiation monotherapy or single-agent chemotherapy alone, respectively. Age, comorbidities, race, and treatment at academic centers were also significant independent predictors of OS. These findings highlight substantial disparities in outcomes and underscore the importance of optimizing treatment strategies, improving access to high-intensity therapies, and supporting timely referral to academic or high case-volume centers, particularly for younger and medically fit patients.

207 Background: CAR-T & bispecific antibodies (BsAb) for large B-cell lymphoma offer deep responses, but have unique toxicities requiring close monitoring. Different practice settings have varied strategies for managing these toxicities, leading to increased costs, healthcare resource use, & reduced quality of life. With no direct comparison, rationale for therapy selection may vary. This study explores provider choices, sequencing strategies & access barriers. Methods: A survey of US-based Hematologists was conducted on practice demographics, therapy availability, preferences, & barriers in LBCL. Responses were analyzed across clinical scenarios. Results: Responses were received from 45 physicians. Availability of CAR-T & BsAb varied with 75% prescribing both, & only BsAb being available at 9% of providers’ centers. There was a strong preference for CAR-T over BsAb—higher among academic vs. nonacademic providers (96% vs. 78%; p = 0.03) & at CAR-T vs. non-CAR-T centers (100% vs. 72%; p = 0.001). Even at BsAb-only centers, preference leaned toward CAR-T, though notably lower compared to CAR-T centers. Among centers without either, 86% preferred CAR-T. Practice volume had no impact. Reasons for favoring CAR-T included perceived better outcomes (55%), shorter treatment (26%), center choice (19%), more experience (48%), & curative potential (21%). BsAb selection was driven by CAR-T unavailability & logistical barriers (distance to specialized center, insurance delays, referral complexity, manufacturing time, & hospitalization needs). Axi-cel was preferred by 69% ( p = 0.0001) vs. other CAR-T for third-line or later due to experience with use, response rates, center choice, & logistical ease. Liso-cel (26%) & Tisa-cel (2%) were chosen for perceived favorable toxicity over Axi-cel. Axi-cel was also preferred second-line vs. Liso-cel (73% vs. 24%; p < 0.0001) for similar reasons. Among BsAb, Epcoritamab was favored by 56% for administration ease (subcutaneous), experience, & center preference; Glofitamab by 42% for shorter duration, experience, & center preference. There was no difference by academic vs nonacademic practice & volume for both CAR-T & BsAb. In patients with prior non-CAR-T anti-CD19 therapy, providers chose CD19 CAR-T over CD20 BsAb (80% vs. 18%; p < 0.0001). For relapse after second-line CAR-T, 78% providers preferred BsAb as the next line over other options ( p < 0.0001) due to more favorable response rates, toxicity profile, & experience with use. Providers prioritized response rates, survival, & toxicity profile in their treatment decisions. Logistics, duration, frequency, & cost were less important. There were no differences based on practice setting & CAR-T experience. Conclusions: Despite higher preference for CAR-T due to perceived superior outcomes, access barriers exist. Efforts to streamline referral pathways, logistics, & expand availability are crucial to improve outcomes.

Abstract Monomorphic posttransplant lymphoproliferative disorders (PTLDs) beyond diffuse large B-cell lymphoma (DLBCL) are rare, biologically heterogeneous entities with limited prospective data to guide treatment. DLBCL-PTLD, which comprises most cases, is managed using approaches informed by prospective phase 2 studies, including reduction in immunosuppression and a risk-adapted sequential immunochemotherapy approach. In contrast, non-DLBCL subtypes such as Burkitt lymphoma, PTLDs of T/NK-cell origin, and plasmacytic variants are less common and are typically treated using strategies extrapolated from established treatment algorithms used in immunocompetent patients and sporadic case reports. Classic Hodgkin lymphoma PTLD, although not classified as monomorphic, represents another distinct and clinically relevant subtype. This review summarizes the epidemiology, clinical features, treatment strategies, and outcomes associated with these less common PTLDs, aiming to provide a practical framework for their management.