Durani, Urshila

ABSTRACTTransplant‐associated thrombotic microangiopathy (TA‐TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high‐risk features on the clinical outcomes of adult patients meeting the updated TA‐TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA‐TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34–283 days). The development of TA‐TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97–4.72). High‐risk features, including concomitant infection, acute graft‐versus‐host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA‐TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow‐up. The most common cause of death among these patients was worsening GVHD (69%; n = 18), followed by infection (11%; n = 3), disease relapse (8%; n = 2), other/unknown causes (8%; n = 2), or TA‐TMA (4%; n = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA‐TMA remains a significant contributor to non‐relapse mortality and is associated with worse survival following alloHCT. Not all high‐risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA‐TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement‐directed therapy, particularly among high‐risk patients.

Abstract Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma involving the brain, cerebrospinal fluid, or retina/vitreous without systemic involvement. Induction with high-dose methotrexate (HD-MTX) followed by consolidation with autologous stem cell transplant (auto-SCT) has become the standard treatment paradigm for most patients. However, limited data are available regarding the efficacy of a maintenance approach with HD-MTX. Herein, we retrospectively reviewed the characteristics and outcomes of 148 patients diagnosed with PCNSL between October 2010 and June 2022, who underwent HD-MTX–based induction therapy followed by either auto-SCT consolidation (n = 70) or HD-MTX maintenance therapy (n = 37). At a median follow-up time of 4.5 years, the progression-free survival (PFS) was 8.3 years and the overall survival (OS) was not reached. Compared to patients who underwent auto-SCT, patients who received maintenance HD-MTX had a higher median age at diagnosis of 72 vs 62 years and a trend toward higher proportion of patients being Eastern Cooperative Oncology Group 2 or higher (41% vs 29%). At 5-years postinduction treatment initiation, the PFS rates in the auto-SCT cohort and HD-MTX maintenance cohort were 74.6% and 72.6%, respectively, and the OS rates were 76.0% and 82.4%, respectively. Overall, there was no significant difference in PFS or OS based on postinduction management strategy. Our data suggest that maintenance HD-MTX may be a reasonable, time-limited treatment strategy for patients with PCNSL responding to initial induction therapy.

Background: Management of cytokine release syndrome (CRS) with chimeric antigen receptor T cell therapy (CAR-T) has evolved in the last decade. First line treatment tocilizumab (toci) was initially given for grade 2 or higher CRS in clinical trials (Toci/CRS≥2). Earlier use of toci in grade 1 CRS was found to be safe without negative impact on clinical response in cohort 4 of ZUMA-1 study for axicabtagene ciloleucel (axi-cel) for B-cell non-Hodgkin lymphoma (NHL; Toci/CRS1). This practice was also adopted for other CAR-T therapies for other disease indications. Subsequently, FDA also updated the package insert for axi-cel in 2021 to include the use of prophylactic dexamethasone (ppx dex) to be given on days 0, 1, 2 of CAR-T infusion based on the results from cohort 6 of ZUMA-1. We examined CRS and ICANS (immune effector cell associated neurologic syndrome) outcome of patients who received FDA approved axi-cel in standard-of-care (SOC) practice with these evolving practices. Of note, adoption of ppx dex has been variable across CAR-T treatment centers in the US (Khurana et al, Blood 2022). At Mayo Clinic Rochester, patients considered high-risk for severe CRS/ICANS (those who received bridging therapy and had LDH above upper limit of normal and/or with secondary CNS involvement or other CNS pathologies) would be considered for ppx dex. Methods: Medical records of patients who received axi-cel in SOC between 2018 and 2023 at Mayo Clinic Rochester were reviewed. ASTCT guideline was used for CRS and ICANS grading. Categorical variables were compared using Chi-squared test and continuous variables were compared using Kruskal-Wallis test. Results: Among 187 pts receiving SOC axi-cel, the median age was 60 years and 121 (65%) were males, 152 (81%) had CRS, of which 73 (39%) were grade ≥2; 97 (52%) had ICANS, of which 65 (35%) were grade ≥2. Of the 152 CRS pts, 54/152 (36%) pts never received toci or ppx/dex. Of the pts who received Toci, 35/152 (23%) received Toci when CRS is at least grade 2 (Toci/CRS≥2), 49/152 (32%) received Toci/CRS1 without ppx dex (Toci/CRS1), and 14 (9%) received ppx dex with Toci given in CRS1 when pts developed CRS (PPX DEX). Baseline demographics were comparable except age (Toci/CRS≥2: 58y; Toci/ CRS1: 63y; ppx dex: 50y; p=0.001) and pre-LD CRP (Toci/CRS≥2: 34mg/L; Toci/ CRS1: 6mg/L; ppx dex: 16mg/L; p=0.002). Pre-LD LDH and ferritin were also comparable. PPX DEX or Toci/CRS1 had significantly lower rate of maximum grade CRS≥2 (PPX DEX: 4 (29%); Toci/ CRS1: 20 (41%); 35 (100%); p<0.001) and duration of CRS (PPX DEX: 2.5d; Toci/ CRS1: 3d; Toci/CRS≥2: 5d; p<0.001). Time to onset of CRS was not statistically different between the 3 groups. Not surprisingly, Toci/CRS1 group had higher overall rate of toci use, compared to . Interestingly, use rate of ≥2 doses of Toci or siltuximab was significantly higher in Toci/CRS1 or PPX DEX (PPX DEX: 8 (57%); Toci/ CRS1: 26 (53%); 9 (26%); p=0.02). Pt who received PPX DEX or Toci/CRS1 had a significantly lower rate of ICANS (PPX DEX: 6 (43%); Toci/ CRS1: 33 (67%); 32 (91%); p=0.001) and rate of max grade ICANS ≥2 (PPX DEX: 3 (21%); Toci/ CRS1: 23 (47%); 27 (77%); p<0.001). The time to onset and duration of ICANS was not different among the 3 groups. Conclusion: Our real-world study shows that earlier use of Toci in grade 1, compared to its first use in grade 2, can result in lower overall incidence of more severe CRS, duration of CRS, incidence of ICANS and more severe ICANS. While we selected patients at higher risk for having more severe CRS in our PPX DEX cohort, experience to date suggests that these patients, compared to toci/CRS>=2 cohort, could also have reduced severity of CRS and ICANS with this updated management.

Introduction: Outcomes from multidisciplinary lymphoma tumor boards in the molecular era are limited, and the effects of transitioning to virtual formats during the COVID-19 pandemic are not well-documented. This study evaluates how the transition of the Mayo Clinic Lymphoma Tumor Board to a virtual format has impacted its effectiveness and operations. The board, part of the International Mayo Clinic Care Network (MCCN), involves case presentations, subspecialist reviews, and collaborative recommendations. Methods: The Mayo Clinic Lymphoma Tumor Board, an integral part of the Mayo Clinic Care Network (MCCN), conducted a comprehensive review of lymphoma cases from 2014 to 2024. The board's review process involves a structured approach including the presentation of clinical case details, radiology and hematopathology findings, proposed treatment options, relevant literature review, and discussions. From 2014 to 2024, the Mayo Clinic Lymphoma Tumor Board reviewed a total of 722 patients. The review process involves a multidisciplinary team, including physicians, pharmacists, clinical research associates, and trainees. Recommendations and changes related to radiology interpretation, pathologic diagnosis, and treatment approaches were documented and tracked prospectively. In March 2020, the board transitioned to a virtual format due to the COVID-19 pandemic. This shift allowed for remote participation and continued collaborative review while maintaining the board's structured approach and documentation practices. Results: In a total of 722 patients, changes in care were identified in 423 patients, including 287 with newly diagnosed lymphoma and 136 with relapse or refractory disease. Among those who experienced changes, 94 had diffuse large B-cell lymphoma, 49 had follicular lymphoma, 39 had marginal zone lymphoma, 36 had classical Hodgkin lymphoma, and 29 had mantle cell lymphoma. Prior to the COVID-19 pandemic, 431 patients were analyzed, with 217 (50.3%) experiencing changes. A total of 268 changes were documented among these patients. Changes in radiologic interpretation occurred in 9 patients (2.1% of 431 total patients). Pathologic diagnosis changes were noted in 42 patients (9.7%). Additional testing was recommended for 73 patients (16.9%), and clinical management was altered for 144 patients (33.4%). After transitioning to a virtual format, 291 patients were reviewed post-COVID, with 206 (70.8%) having recommended changes. The total number of change recommendations was 322, reflecting increases across all components compared to previous data, with adjustments for varying numbers of patients reviewed. Specifically, radiologic interpretation changes occurred in 21 patients (7.2%), pathologic diagnosis changes in 57 patients (19.6%), additional testing recommendations for 85 patients (29.2%), and clinical management alterations in 159 patients (54.7%). Conclusion: Transitioning to a virtual format in the Mayo Clinic Lymphoma Tumor Board's continued to demonstrate the effectiveness, with increased changes in diagnostic interpretations and clinical management. These results illustrate the potential of virtual tumor boards to improve collaborative decision-making and adapt to evolving clinical needs.

Introduction: Patients with non-Hodgkin Lymphoma (NHL), especially adolescents and young adults, can face late effects from treatment, including decreased fertility. Due to time constraints prior to treatment initiation and sometimes financial limitations, implementing fertility counseling and referral-based guideline care remains challenging. We aim to understand the occurrence and predictors of fertility counseling and preservation in patients with NHL in the Lymphoma Epidemiology of Outcomes (LEO) cohort study. Methods: The LEO cohort prospectively enrolled newly diagnosed patients with NHL from 2015-2020 at 8 academic medical centers in the US. Clinical. Treatment data were abstracted from medical records, pathology was reviewed and classified by a LEO pathologist, and participants completed a self-administered questionnaire. Participants were then prospectively followed to identify outcomes and collect additional patient reported data, including a survivorship questionnaire at follow-up 3 years (FU3) after diagnosis that included items on fertility counseling and preservation. The questionnaire contained two fertility questions analyzed: whether healthcare providers discussed the impact of lymphoma treatment on fertility, and whether providers discussed the process of fertility preservation. This analysis was based on participants aged 18-50 years at enrollment and who completed the fertility questions at FU3. Women who had undergone natural or procedural menopause and men who had undergone vasectomy pre-treatment were excluded. We estimated the association of demographic and clinical factors with fertility preservation using odds ratios (ORs) and 95% confidence intervals (CI) from univariate and multivariable logistic regression models. Results: Seventy-seven patients were included in the analysis: 36 females (46%) and 41 males (53%). The median age of diagnosis was 40 years (IQR 30-45), and 36 (47%) participants were in the age 18-39-year category. Participant self-identified race/ethnicity was 69% non-Hispanic White, 22% Hispanic, 4% Black and 3% Asian. Sixty (78%) patients were treated with alkylators, 12 (15.6%) with non-alkylators, and 5 (6.5%) with radiation. Fifty-five (71%) of the patients were classified as having aggressive lymphoma, with follicular, extranodal marginal zone, primary cutaneous follicle center, and nodal marginal zone B-cell lymphoma defined as indolent and remaining subtypes aggressive. Around 6% of female patients underwent fertility preservation after lymphoma diagnosis, compared to 12.2% of male patients. All the patients who had undergone fertility preservation after lymphoma diagnosis were in the 18-39-year age group. On univariate analysis, females were more likely to have undergone fertility toxicity and preservation discussions compared to males, with 72% of females and 59% of males recalling a discussion regarding fertility (OR 1.8, 95% CI 0.7-4.9, p=0.21). Those age 18-39 were significantly more likely to have undergone fertility discussion compared to those aged 40-50 (OR 10.2, 95% CI 3.3-39.2, p<0.001). Patients treated with alkylating therapy were significantly more likely to undergo fertility discussion when compared to those on non-alkylating therapy (OR 9.0, 95% CI 2.3-45.5, p<0.01). In addition, 75% of those with aggressive lymphoma compared to 41% of patients with indolent lymphoma had fertility discussion (OR 4.2, 95% CI 1.5-12.4, p=0.01). White patients were significantly less likely than Hispanic, Black and Asian patients to have fertility discussion (OR 0.2, 95% CI 0.04-0.6, p<0.01). In the multivariable analysis, alkylating therapy (OR 8.9, 95% CI 1.6-66.7) and age 18-39 years (OR 10.9, 95% CI 2.9-55.3) remained significant predictors of fertility discussion; White race was also trending towards significance (OR 0.2, 95% CI 0.04-1.0, p=0.08). Aggressive lymphoma subtype was not a significant predictor of fertility discussion. Conclusions: In this cohort of lymphoma survivors 3 years post-diagnosis, we found that Hispanic patients, those diagnosed at a younger age and exposed to alkylating chemotherapy agents were significantly more likely to undergo discussions regarding the effects of lymphoma treatment on fertility. Our study highlights the importance of all cancer patients of childbearing age having the opportunity to address fertility concerns during clinic visits.

Background: Financial toxicity (FT), or the negative impact of medical expenses experienced by patients, is a known adverse effect of cancer treatment that result in worse health outcomes for patients. However, there is limited literature investigating FT in lymphoma with even less data on predictors such as age, gender, and socioeconomic factors. As lymphoma treatment options expand, it is vital to understand the impact of these treatments on patients' financial well-being. We investigate FT through patient reported outcomes from the Lymphoma Epidemiology of Outcomes (LEO), a large multi-institution prospective cohort study of non-Hodgkin lymphoma (NHL). Methods: Patients with newly diagnosed NHL were enrolled into the LEO cohort from 2015-2020. Clinical, pathology and treatment data were abstracted from medical records, and participants were offered self-administered surveys at enrollment and selected follow-up time points. Participants were included if they completed at least four of six survey questions on FT adapted from the Medical Expenditure Panel Survey (MEPS) within the first year after diagnosis. Questions focused on either material hardship (unable to cover costs; file for bankruptcy; borrow money; work extra job or hours) or psychological stress (worried about paying large medical bills). We evaluated FT as answering positively to any question (any vs none). Associations with FT were evaluated using chi-squared tests. All analyses were performed using R (v4.2.2). Results: 3202 patients completed at least four survey questions relating to FT. Mean age at diagnosis was 62 years (18-94), 56% were male, and majority identified as white (90%). Characteristics associated with FT are reported (p<0.001). FT was more likely in younger patients: 18-25 years (64%, 30/47), 26-44 years (73%, 299/313), and 45-64 years (58%, 799/1375) as compared to those 65-79 years (36%, 459/1272) and ≥80 years (35%, 69/195). FT was highest in patients without a high school diploma (54%, 45/84), followed by patients with a high school diploma (52%, 209/402), and an associate's degree (57%, 358/627). It was lowest in patients with a bachelor's (45%, 224/296) or post-graduate degree (39.6%, 216/545). Higher FT was seen in those receiving disability income (65%, 47/72); whereas less FT was seen in retired patients (36%, 299/828). FT rates inversely correlated with income: 65% for income < $21,000 (184/283), 61% for $21,000- $39,999 (224/370) and 60% for $40,000-$65,999 (293/491). Lower FT noted for income range of $66,000-$106,000 (47%, 323/681) or > $106,000 (37%, 324/872). Patients separated from a partner (82.9%, 19/23) had the highest FT, followed by patients living with a partner (64%, 48/75), divorced (56%, 103/184), and never married (53.4%, 79/148). Patients who were married (47%, 793/1672) or widowed (41%, 60/146) reported the lowest FT. Higher FT was reported in DLBCL (55%, 631/1146), MCL (55%, 172/315), and TCL (53%, 119/226) when compared to FL (44%, 327/746), MZL (44%, 137/316), and other NHL (44%, 200/453). This is likely related to treatment as more FT was seen in patients who received an anthracycline and/or alkylator containing therapy (54%, 1066/1963) versus non-systemic (43%, 120/278) and observation (35%, 168/483). In multivariable analyses, FT strongly correlated with age at diagnosis, household income, and treatment type. The odds ratio and 95% confidence intervals for the most significant category within each variable are as follows: age per 1 year (0.96, [0.95-0.97]), income > $106,000 vs < $21,000 (0.28, [0.21-0.38]), and observation vs anthracycline and/or alkylator (0.56, [0.44-0.71]). Conclusion: Nearly 50% of patients with lymphoma experience FT, seen as material hardship and psychological stress, within the first year of diagnosis. Patients with a younger age (18-44), less education, and lower household income reported higher levels of FT; whereas those who were retired or married/widowed reported lower FT. Lymphoma subtypes that require more anthracycline and/or alkylator containing therapy imposed higher FT. Understanding these risk factors can help clinicians identify patients who may benefit from additional resources during lymphoma management.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has shown substantial promise in treatment of hematological malignancies, including non-Hodgkin Lymphoma (NHL). A subset of patients develop prolonged cytopenia, comprising quality of life, increasing healthcare utilization, and imparting considerable morbidity and mortality. Therapy-related myeloid neoplasms (t-MN), typically seen in patients who receive DNA-damaging agents such as radiotherapy and alkylators, have also been observed in CAR-T recipients. CAR-Hematotox score predicts the development of hematotoxicity in CAR-T recipients using laboratory parameters obtained at lymphodepleting (LD) chemotherapy, a timepoint when the patient has already gone through leukapheresis thus committed to the CAR-T process. Therefore, it is critical to identify patients at the highest risk of prolonged cytopenia and/or t-MN prior to apheresis, making it possible for a better triage of those who will proceed with CAR-T and those who might benefit from other strategies. Methods: A retrospective analysis was conducted in NHL patients who received commercial CAR-T products between January 2018 and March 2024 at Mayo Clinic Rochester, Arizona and Florida. Clinical and laboratory data including age, hemoglobin (Hb), absolute neutrophil count (ANC), platelet (PLT), ferritin, and LDH, obtained at the initial CAR-T evaluation, typically within 1 week of leukapheresis, were used for analysis. Prior lines of therapies including autologous stem cell transplant (ASCT) were collected. Prolonged cytopenias were defined as Hb < 8 g/dL, ANC < 0.5 x 109/L, and/or PLT < 50 x 109/L at 3 months after CAR-T. t-MN was diagnosed per WHO 2016. For prolonged cytopenia, the optimal cutoff points for continuous variables were determined by maximizing the sum of sensitivity and specificity. Logistic regression was then used to determine the factors associated with cytopenia at 3 months post-CAR-T. For t-MN, maximally selected log-rank statistics was used to determine the optimal cutoffs. We used competing risk analysis to determine the factors associated with development of t-MN. Death without t-MN was considered a competing risk. For both analyses, the factors with P < 0.1 in univariate analysis (UVA) were included in multivariate analysis (MVA). Results: Among the 387 NHL patients, with a median follow-up of 11 months (95% CI 8.7 - 12.2 months), 56 (14.4%) developed (41, 10.5% with 1 cytopenia; 14, 3.6% with 2 and 1, 0.2% with cytopenia in all 3 lineages), 20 (5.2%) developed and 315 (81.2%) did not have either. Factors associated with prolonged cytopenia: were age >, PLT ≤ 150, ferritin ≥ 600, and LDH ≥ 250. Univariate analysis identified baseline Hb, ANC, PLT and ferritin to be significantly associated with prolonged cytopenia. MVA identified Hb ≤ 11 (HR = 1.98; 95% CI 1.03-3.85, P = 0.042) and PLT ≤ (HR = 2.56; 95% CI 1.39-4.78; P = 0.003) to be associated with the development of prolonged cytopenia. Factors associated with t-MN:were age > 65 years, Hb ≤ 9 g/dl, ANC < 3.8, PLT ≤ 80, Univariate analysis identified age, Hb, ANC, PLT, ferritin, and ≥ 3 prior lines of treatment to be significantly associated with t-MN. On MVA, age ≥ 65 (HR = 3.91; 95% CI 1.52-10.03; P = 0.004), Hb ≤ 9 (HR = 3.49; 95% CI 1.38-8.85; P = 0.008), ferritin ≥ 300 (HR = 3.06 ; 95% CI 1.08-8.67; P = 0.035) and ≥ 3 prior lines of therapy (HR = 3.25; 95% CI 1.33-7.94 ; P = 0.010) were associated with t-MN development. Association of prolonged cytopenia with t-MN development: Prolonged cytopenia was noted in 45% of patients who developed t-MN and 15% of those who did not (P = 0.002). Cumulative incidence of t-MN at 1 year was 3.3% and the presence of prolonged cytopenia was associated with a higher 1of t-MN (HR 8.93, 95% CI 2.15 - 37.1, P = 0.003). Conclusions: Readily accessible clinical and lab data such as blood count and inflammatory markers at the time of CAR-T evaluation were associated with the development of prolonged cytopenias. Similarly, advanced age, anemia, high ferritin levels and history of ≥3 lines of therapy were associated with the development of t-MN. These findings, when validated in larger dataset, can be used for patient counseling and therapy selection by identifying patients at high-risk of developing hematotoxicity and/or t-MN development.

Background: Indolent non-Hodgkin lymphomas (iNHL) are incurable and disproportionately affect adults age >65 in whom frailty and functional impairment can impact disease management. The Vulnerable Elders Survey (VES-13) is a 13-item screening tool that incorporates age, self-rated health, physical function limitations, and functional disabilities to identify vulnerable older community-dwelling adults. Adults with a VES-13 score of >3 have a fourfold increased risk of death or functional decline over 2 years as compared to adults with a score <3 (Saliba et al, JAGS 2001). Our team previously showed that VES-13 >3 was associated with a higher risk of 1-year mortality in NHL (OR 3.26, 95% CI 2.15-4.96, Fama et al, ASH 2019), including in adults age <65. In this study, we determined whether VES-13 scores >3 were associated with quality of life (QOL) changes in adults with iNHL across the age spectrum. Methods: We used the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study to identify adults enrolled from 2015-2020 with grade 1-3A follicular and marginal zone lymphoma (FL, MZL) who completed the VES-13 at enrollment and QOL surveys at enrollment and follow-up. The LEO Cohort Study enrolls participants within 6 months of diagnosis and collects information on disease status, QOL, health behaviors, and patient-reported functional assessment. For this analysis we included QOL measured using the Functional Assessment of Cancer Therapy-General (FACT-G) at years 1 and 2 post-enrollment. The FACT-G total score was the sum of 4 subscales (range): physical (PWB, 0-28), social/family (SFWB, 0-28), emotional (EWB, 0-24), and functional (FWB, 0-28) well-being. A higher FACT-G total score (range 0-108) indicated better overall QOL. VES-13 scores ranged from 0 (lowest risk for death or decline) to 10+ (highest risk). Generalized linear mixed models evaluated changes in QOL from baseline based on VES-13 score >3 (vulnerable) vs <3 (non-vulnerable), within groups by age at enrollment >65 and <65. Results: Our study included 1,186 participants: 42% age >65, 54% female, 84% non-Hispanic White, 10% Hispanic, 3.3% Black, and 1.4% Asian/Pacific Islander. Most (68%) were diagnosed with FL. FLIPI was high risk for 20%, and MALT-IPI was high risk for 23%. In the VES-13 <3 group, the mean (SD) baseline FACT-G total score was 86.5 (12.0), PWB 21.0 (3.5), SFWB 24.3 (4.3), EWB 18.8 (3.7), and FWB 22.3 (4.9). In the VES-13 >3 group, the mean (SD) baseline FACT-G total score was 70.4 (16.5), PWB 15.4 (5.6), SFWB 22.3 (5.5), EWB 17.5 (4.5), and FWB 15.3 (6.4); all significantly lower than the VES-13 >3 group (all p<0.01). In adults <65, 63 (9%) had a VES-13 >3, which was associated with a significant improvement from baseline in PWB at years 1 and 2 when compared to VES-13 <3 (changes in baseline PWB were 2.1, 2.9 for VES-13 >3 vs 0.2, 0.1 for VES-13 <3, all p<0.05). Similarly, we observed improvement in FWB from baseline at years 1 and 2 in the VES-13 >3 vs <3 group (2.4, 2.9 vs 0.4, -0.1, respectively all p<0.05). The VES-13 >3 group had a decline in their EWB at 1 year vs the VES <3 group (-0.5 vs 1.2, respectively, p=0.003). At year 2, total FACT-G improved from baseline in the VES-13 >3 group (5.6 for VES-13 >3 vs -0.5 for VES-13 <3, p=0.002). SFWB changes from baseline did not differ between groups. In adults >65, 83 (17%) had a VES-13 >3, which was associated with a significant improvement from baseline PWB (1.3, 1.5 for VES-13 >3 vs. 0.1, -0.1 for VES-13 <3), FWB (3.3, 2.2 for VES-13 >3 vs. 0.5, 0.1 for VES-13 <3), and total FACT-G score (5.2, 3.4 for VES-13 >3 vs. 1.0, -0.4 for VES-13 <3) when compared to VES-13 <3 at years 1 and 2 (all p<0.05). SFWB and EWB changes from baseline did not differ between groups. While there was improvement from baseline PWB and FWB in the VES-13 >3 group, QOL scores across all subscales remained below the VES-13 <3 group in the study period for both age groups. Statistical significance was maintained in models adjusted for baseline characteristics, including initial treatment strategy (observation, systemic, vs local) for both age groups. Conclusion: Although the vulnerable group reported worse QOL throughout the study period compared to the non-vulnerable group, survivors in the vulnerable group saw greater improvement in their physical and functional well-being at 1- and 2-years post-diagnosis. Additional analyses are underway to identify drivers of improvement in physical and functional well-being in vulnerable adults diagnosed with iNHL.

Background: Mature T-cell lymphomas (MTL) are a heterogenous group of diseases representing about 10-20% of non-Hodgkin lymphomas (NHL). Standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy yields poor long-term outcomes. Allogeneic hematopoietic cell transplantation (allo-HCT) is often considered as consolidation to improve outcomes, especially in younger patients. Methods: The study included adult patients (pts) with MTL who received an allo-HCT at Mayo Clinic (Rochester, Arizona and Florida) and the City of Hope Cancer Center between 2007 and 2023. Patients with cutaneous T-cell lymphomas (mycosis fungoides/Sezary syndrome) were excluded. The primary aim of the study was to evaluate long-term outcomes of allo-HCT in patients with MTL. Primary endpoints included progression-free (PFS), overall survival (OS), relapse rates, non-relapse mortality (NRM), and cumulative incidence of acute and chronic graft vs host disease (aGVHD and cGVHD). Our second aim was to assess the impact of specific disease and transplant related factors on outcomes of allo-HCT in MTL. These included a) disease status prior to allo-HCT, b) the intensity of the conditioning regimen, c) inclusion of total body irradiation (TBI) in conditioning regimens and the use of posttransplant cyclophosphamide (PTCy) based GVHD prophylaxis Results: A total of 75 pts, median age 48 (22-72) years, with MTL underwent allo-HCT between 2007 and 2023 and were included in the study population. Peripheral T cell lymphoma not otherwise specified (PTCL-NOS; n=42, 56%) was the most common histology followed by angioimmunoblastic T cell lymphoma (AITL; n=13, 17%). Patients had a median of 3 (range 1-8) prior therapies and 26 (35%) pts had undergone a prior autologous HCT (auto-HCT). At the time of allo-HCT, 45 (63%) pts were in complete remission (CR) and 26 (36%) pts were in partial remission (PR). The most common donor source was HLA-matched unrelated donor (MUD; n=34, 45%) and matched related (MRD; n=24, 32%) followed by haploidentical donors (haplo; n=8, 10.7%), mistmatched unrelated donors (MMUD; n=7, 9.3%) and umbilical cord blood (UCB; n=2, 2.6%). Fifty-four pts (72%) received reduced intensity conditioning (RIC) and 20 (26.7%) received total body irradiation as part of their conditioning regimen. The median radiation dose was 1200cGy. Ten pts (13%) received PTCy-based GVHD prophylaxis. Median follow-up of was 3 yrs (0.05-11.34). The 5-yr PFS and OS were 64.2% (53.5%-77%) and 71.3% (61.3%-82.9%), respectively; cumulative incidence of relapse and NRM were 14.5% (5.2 - 23%) and 23.5% (12.2%-33.4%), respectively. Cumulative incidence of grade II-IV and grade III-IV aGVHD at 100 days was 45.3% (32.3%-55.9%) and 9.8% (2.6%-16.5%), respectively. One-year rate of all grade cGVHD was 50.7% (36.5%-61.8%). Patients who underwent allo-HCT while in complete remission compared to those in partial remission were noted to have superior survival with OS of 77.4% vs. 60.7% (p=0.022); no difference was noted between the two groups regarding PFS and incidence of relapse. No difference in long-term outcomes was observed based on the intensity of conditioning regimens but patients who received conditioning regimens containing TBI vs those who did not were noted to have inferior PFS of 44.9% vs 70.5% (p=0.019), with no difference in OS (58.4% vs 75.6% [p=0.059]), relapse rates (30.4% vs 10.7% [p=0.086]) and NRM (30.5% vs 20.3% [p=0.18]). Patients who received PTCy based vs. non-PTCy based GVHD prophylaxis had lower rates of chronic GVHD at 1 yrs (22% vs 56% [p=0.038]) with no difference in other outcomes. Conclusion: Results of our analysis show that allo-HCT represents a curative option for patients with MTL with excellent long-term outcomes. These outcomes were further improved for patients who achieved a complete remission prior to allo-HCT. The intensity of the conditioning regimen did not affect outcomes but TBI containing conditioning regimens were associated with adverse PFS. Within the limitations of a retrospective analysis and a relatively small sample, these data suggest that, a non-TBI RIC regimen, especially when combined with PTCy based GVHD prophylaxis can lead to long term disease control with limited morbidity.

Background: In the ZUMA2 study, a higher peak chimeric antigen receptor (CAR) T cell expansion correlated with better outcomes in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) receiving brexucabtagene autoleucel (brexu-cel). However, in clinical practice, peak CAR T cell expansion is not routinely assessed for. Since patients receive lymphodepleting agents prior to CAR T cell infusion, it is hypothesized that peak absolute lymphocyte count (ALC), which can be easily measured, in the first two weeks after CAR T cell infusion represents peak CAR T cell expansion. Our group previously showed that peak ALC was associated with response durability and outcomes in patients with R/R large B-cell lymphoma receiving axicabtagene ciloleucel. In this retrospective study, we assessed the association of peak ALC with clinical outcomes after brexu-cel infusion in patients with R/R MCL. Methods: Patients with R/R MCL who received brexu-cel between March 2020-March 2024 at Mayo Clinic were included in this analysis. Peak ALC was defined as maximum ALC value in the first 14 days after CAR T cell infusion. Progression-free survival (PFS) was defined as time from CAR T cell infusion to lymphoma relapse, progression, or death, and overall survival (OS) was defined as time from to CAR T cell infusion to death. The optimal cutoff point for peak ALC that correlated with PFS was determined by the log-rank method using the Cutoff Finder application, a computational method which fits Cox proportional hazard models to the dichotomized variable and survival. The optimal cutoff was the point with the most significant PFS split by log-rank test. Results: A total of 43 patients were identified. The median age at time of CAR T cell infusion was 68 years (IQR 58, 73). 34 (79%) were male, 28 (74%) had Ki-67 >30%, 14 (33%) had blastoid or pleomorphic histology, and 19 (44%) had TP53 mutation or deletion. Median number of prior lines of therapy was 3 (IQR 2, 4) and 13 (30%) received prior autologous stem cell transplant. 32 (74%) received bridging therapy prior to CAR T cell infusion. All patients received fludarabine plus cyclophosphamide for lymphodepletion. The best overall response rate was 88%, with a complete response rate of 84%. After a median follow-up of 25.6 months (95% CI 14.4-31.4), the median PFS and OS were 16.6 (95% CI 8.6-NE) and 35.1 (95% CI 24.5-NE) months, respectively. The incidence of cytokine release syndrome (CRS) was 95% (4.7% grade ≥3). The median time to initial CRS and maximum grade CRS onset was 4.5 days (IQR 1, 6.25) and 5.5 days (IQR 2.75, 7), respectively. The incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) was 65% (18% grade ≥ 3). The median time to initial and maximum grade ICANS onset was 9 days (IQR 6, 11) and 10.5 days (IQR 7, 12), respectively. The median ALC at time of CAR T cell infusion was 0.03 x109/L (IQR 0.02, 0.05). Among 37 patients with identifiable ALC peaks, the median ALC peak was 0.84 (IQR 0.41, 2.45) and the median time to peak ALC was 12 days (IQR 9, 12). 6 patients had no identifiable peak ALC due to no frequent CBC differentials post CAR T cell infusion. A peak ALC of ≥0.45 × 109/L correlated significantly with PFS, with median PFS not reached for the group with peak ALC of ≥0.45 × 109/L (n=27) compared to 9.3 months for the group with peak ALC of <0.45 × 109/L (n=10) and a 1-year PFS rate of 68% vs 33% (p=0.02). OS was also significantly higher in patients with a peak ALC of ≥0.45 × 109/L (median OS not reached vs 11 months, 1-year OS rate of 84% vs 44%, p=0.01). The incidence of ICANS was significantly higher (74% vs 30%, p=0.02) in patients with a peak ALC of ≥0.45 × 109/L. Numerically, the group with peak ALC of ≥0.45 × 109/L had a later onset of initial and maximum grade ICANS, but the difference was not statistically significant. Peak ALC was not associated with ICANS severity. There was a trend towards higher incidence of CRS (100% vs 80%, p=0.07) and earlier CRS onset (3 vs 5 days, p=0.07) in the high peak ALC group. There was no difference in CRS severity. Conclusion: Peak ALC after CAR T cell infusion was significantly associated with better PFS and OS and higher incidence of ICANS in patients with R/R MCL receiving brexu-cel. Peak ALC may serve as a surrogate measure for peak CAR T cell expansion in routine practice, but confirmatory studies are needed. Larger studies are warranted to confirm the association of peak ALC with PFS, OS and toxicities in patients with R/R MCL receiving brexu-cel.