Habermann, Thomas M.

Background: Immunochemotherapy is the current standard-of-care frontline therapy for diffuse large B-cell lymphoma (DLBCL). Our group previously reported that addition of the mTOR inhibitor everolimus to R-CHOP resulted in excellent efficacy in the Alliance N1085 trial (Witzig TE et al, Blood Cancer J, 2017, 7(6):e576), with 23 of 24 patients achieving event-free survival at 24 months (EFS24), supporting further investigation of PI3K/mTOR targeting in DLBCL. New insights into molecular classification of DLBCL suggest that multiple genetic subtypes of DLBCL (eg, MCD, BN2, ST2, and EZB per LymphGen classification) may be susceptible to PI3K/mTOR targeting. Therefore, we conducted a phase 1/1b trial to investigate the safety and efficacy of combination therapy with a novel PI3K inhibitor parsaclisib and standard immunochemotherapy. Methods: Adult patients with newly diagnosed DLBCL were eligible if any of the following was present: 1) non-GCB subtype per the Hans algorithm; 2) protein expression of either MYC (≥40%) or BCL2 (≥50%) by immunohistochemistry; or 3) MYC rearrangement by FISH. Patients with high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements were also eligible. Phase 1 followed a 3+3 design to determine the maximum tolerated dose (MTD) of parsaclisib (plus R-CHOP) to be used in Phase 1b (dose expansion). The primary efficacy endpoint in phase 1/1b was complete response (CR) rate by PET. A polatuzumab vedotin (Pola) safety lead-in cohort was added later to explore the safety and efficacy of parsaclisib (at MTD) plus Pola-R-CHP. Results: From July 2020 to May 2023, 50 patients were enrolled; 1 patient withdrew consent before study treatment and was excluded from this analysis. Nine patients were treated in Phase 1, 33 in Phase 1b, and 7 in the Pola cohort. The median age at diagnosis was 66 years (range 20-86), and 20 (41%) were female. Two (4%) patients had ECOG PS ≥2, 26 (53%) had elevated LDH, 19 (39%) had >1 extranodal site, 37 (76%) had stage III/IV, and 25 (51%) had high-intermediate or high-risk International Prognostic Index (3-5). 23 (47%) had non-GCB subtype, 23 (46.9%) had MYC or BCL2 single expression, 21 (42.9%) had MYC/BCL2 double expression, and 6 (12%) had MYC rearrangement (2 with BCL2 and/or BCL6 rearrangements). In Phase 1, 3 patients were treated at dose level 1 (parsaclisib 20 mg QD, d1-10) and 6 at dose level 2 (parsaclisib 20 mg QD, d1-14). No dose limiting toxicity was observed. Therefore, dose level 2 for parsaclisib was the MTD and was used in Phase 1b. In the Pola cohort (n=7), only 1 of 6 evaluable patients experienced significant toxicity (grade 3 diarrhea). Among all 49 patients, the most common treatment-related adverse event (TRAE) of any grade included neutropenia (83.7%), thrombocytopenia (79.6%), leukopenia (77.6%), lymphopenia (71.4%), anemia (71.4%), nausea (63.3%), fatigue (40.8%), peripheral sensory neuropathy (36.7%), constipation (24.5%), and diarrhea (22.4%), and the most common grade ≥3 TRAE included neutropenia (71.4%), leukopenia (69.4%), lymphopenia (49.0%), thrombocytopenia (20.4%), anemia (16.3%), febrile neutropenia (6.1%), and diarrhea (6.1%). In Phase 1/1b (n=42), the overall response rate (ORR) to parsaclisib plus R-CHOP was 97.6%, and the CR rate was 90.5%. After a median follow-up of 28.5 months (95% CI 27.7-32.7), the estimated 2-year progression-free survival (PFS) rate was 84.6% (95% CI 73.9-96.8), and the estimated 2-year overall survival (OS) rate was 95.1% (95% CI 88.7-100.0). In the Pola cohort, the ORR to parsaclisib plus Pola-R-CHP was 100% and the CR rate was 100%. After a median follow-up of 15.6 months (95% CI 13.5-NE), 1 patient had disease relapse at 11.95 months, and all patients were alive. Conclusions: Addition of the PI3K inhibitor parsaclisib to R-CHOP or Pola-R-CHP immunochemotherapy is considered safe in patients with newly diagnosed DLBCL. Combination of parsaclisib and standard immunochemotherapy resulted in high ORR and CR rate and encouraging preliminary PFS and OS outcomes patients with high-risk DLBCL. These data support further investigation of PI3K/mTOR targeting in newly diagnosed DLBCL in future trials.

Background: Approximately20% of patients with follicular lymphoma (FL) will experience disease progression or death within two years of years (POD24) of immunochemotherapy (IC) (Casulo et al, JCO 2015). A proportion of patients with POD24 have histologic transformation (HT), which heightens the risk of lymphoma-related death (Freeman et al, Blood 2019). To clarify the impact of HT on prognosis in POD24, we analyzed data from the Lymphoma Epidemiology of Outcomes (LEO) Consortium of Real-World Evidence (CReWE) to compare differences in outcomes among patients with POD24 with retained FL histology versus POD24 with HT. Methods: This was a multicenter study among 8 academic cancer centers. Eligible patients hadgrade 1-3a FL at diagnosis between 2003 and 2022, with POD24 following first line IC treatment with BR, R-CHOP, or R-CVP. POD24 was defined as disease recurrence within 24 months of IC. Patients with prior lines of treatment for FL were excluded. Patients with HT at first line IC were excluded. Biopsy at POD24 was obtained at the discretion of the treating physician. Three groups of POD24 were defined: POD24 with biopsy-proven retained FL histology (POD24_FL), POD24 with biopsy-proven HT to aggressive lymphoma (POD24_HT), and POD24 either without a biopsy or indeterminate histology on biopsy (POD24_I). We evaluated second-line treatments at time of POD24. Survival probabilities from second-line treatment initiation were estimated by the Kaplan-Meier method. Results A total of1,122 patients with FL were screened and308 patients with POD24 were identified.Median age at POD24 was 58 years (IQR 50-65).Among available data, race and ethnicity was reported as 76% non-Hispanic White, 3% non-Hispanic Black/African American, 9% Hispanic/Latino (any race), and 1% other minorities. First line therapy was R-CHOP in45% (140/308), BR in 33% (102/308) and R-CVP in 21% (66/308). Most patients (52%) had biopsy-proven retained FL at POD24 (162/308); 30% had no biopsy or indeterminate histology at POD24 (94/308), and 17% had biopsy-proven HT at POD24 (52/308). In the POD24_HT group, 52% received R-CHOP and 21% received intensive salvage chemotherapy as second line therapy. Patients with POD24_FL and POD24_I had similar rates of salvage chemotherapy (21% and 18%), BR (13% and 18%), R-CHOP (19% and 24%), and targeted therapies (8% and 5%), respectively, at second line. Consolidative autologous stem cell transplant was more common in POD24_HT patients at 21% versus 16% in POD24_FL and 6% in POD24_I. Patients with POD24_HT had significantly worse overall survival (OS) compared to POD24_FL (ref), with a hazard ratio of 3.79 (95% confidence interval [CI] 2.46-5.84), even after adjusting for age, FLIPI score, and first-line IC treatment. At 5 years, patients with POD24_HT had OS of 31% compared with an OS of 71% for patients with POD24_FL. Patients with POD24_I had similar outcomes to those with POD24_FL (5-year OS 75% versus 71%, respectively). Event-free survival (EFS) was also significantly lower in POD24_HT compared to POD24_FL: At 2 years, EFS was 27% for POD24_FL (21-35%) and 10% for POD24 _HT (4-23%). At 5 years, lymphoma remained the leading cause of death among patients with POD24, with 20% probability of lymphoma-related death in those with POD24_FL (95% CI 14.2-27.8) compared to 53% probability of lymphoma-related death in patients with POD24_HT (95% CI 40.6-70.7). Conclusions: In our multicenter cohort, we identified remarkable differences between the two biopsy-demonstrated entities of POD24 (i.e., with and without HT). Patients without a biopsy or indeterminate histology had similar outcomes as those with POD24_FL. Patients withearlyrelapse of FL after first-line IC remain a heterogeneous group with poor outcomes and a heightened risk of lymphoma-related mortality particularly compared with nonPOD24 groups. Even with retained FL histology, patients with POD24 had 20% probability of lymphoma-related death within 5 years of second-line treatment initiation. We demonstrate that poor survival is driven in part, but not entirely, by HT. Despite most patients receiving appropriate aggressive treatment, those with POD24_HT represent a distinctly vulnerable population warranting further study in directed prospective studies of both FL biology and clinical trials.

Background Mantle cell lymphoma (MCL) is more common in males, with a male to female ratio of approximately 3:1. However, it is unclear whether disease characteristics and survival outcomes differ by sex. Additionally, the impact of race and ethnicity in MCL is understudied due to underrepresentation of minorities in clinical studies and trials. In this study, we utilized the National Cancer Database (NCDB) to examine patient and disease characteristics and survival outcomes of MCL by sex, race and ethnicity. Methods Patients diagnosed with MCL in 2004-2020 were identified from NCDB. Patient and disease characteristics were compared between groups using Chi-squared tests. Overall survival (OS) analysis was performed using the Kaplan-Meier method and the Cox proportional hazards model. Results A total of 35,135 patients was included. The median follow-up was 83.0 months (95% CI 81.9-84.1). 24,980 (71.1%) patients were male and 10,155 (28.9%) were female. Females had more elderly (age ≥65: 65.9% vs 59.0%; p<0.001), lower Charlson-Deyo Score (CDS ≥2: 7.0% vs 8.6%; p<0.001) and fewer stage III-IV diagnoses (80.5% vs 82.6%; p<0.001). Females were less likely to receive upfront treatment (80.7% vs 85.3%; p<0.001), treatment at academic centers (36.8% vs 40.9%; p<0.001) or transplant (11.0% vs 13.7%; p<0.001). Compared to males, females were more likely to live in metropolitan areas (83.7% vs 81.6%; p<0.001), had similar incomes, had more Medicare (60.4% vs 53.1%) and fewer private insurance (33.2% vs 38.6%; p<0.001). Female patients had better OS, with a median OS of 76.0 (95% CI 72.4-79.6) vs 67.8 months (95% CI 65.9-69.6; p<0.001). In the multivariable Cox model adjusting for age, race, ethnicity, CDS, stage, upfront treatment (vs surveillance or no treatment), facility (academic vs nonacademic), transplant, residence (metropolitan vs urban or rural) and insurance, female sex remained associated with superior OS (HR 0.84, 95% CI 0.793-0.890; p<0.001). For race, 32,399 (92.2%) patients were White, 1,465 (4.2%) were Black, 942 (2.7%) were others and 329 (0.9%) were unknown. Compared to White patients, Black patients had fewer elderly (52.9% vs 61.7%; p<0.001), higher CDS (≥2: 11.4% vs 7.9%; p<0.001), similar stage III-IV (80.7% vs 82.1%; p=0.276) and upfront treatment (84.7% vs 84.0%; p=0.074), were more likely to be treated at academic centers (50.6% vs 38.9%; p<0.001), were less likely to receive transplant (11.1% vs 13.0%; p=0.042), were more likely to live in metropolitan areas (91.0% vs 81.5%; p<0.001), had lower income, had more uninsured (4.4% vs 2.0%) and Medicaid (9.8% vs 3.7%) and fewer Medicare (47.4% vs 56.0%; p<0.001). Black and White patients had similar OS, with a median of 67.9 (95% CI 57.5-78.2) vs 69.6 months (95% CI 67.8 vs 71.3; p=0.697). In the multivariable Cox model, Black vs White race was not associated with OS (HR 1.086, 95% CI 0.952-1.240; p=0.219). For ethnicity, 31,717 (90.3%) patients were non-Hispanic, 1,894 (5.4%) were Hispanic and 1,534 (4.3%) were unknown. Hispanics had fewer elderly (51.3% vs 61.5%; p<0.001), lower CDS (≥2: 6.4% vs 8.2%; p=0.018), similar stage III-IV (81.2% vs 82.1%; p=0.467), were more likely to receive upfront treatment (86.0% vs 83.9%; p<0.001), more likely to be treated at academic centers (49.9% vs 39.5%; p<0.001), equally likely to receive transplant (13.0% vs 13.1%; p=0.943), more likely to live in metropolitan areas (95.4% vs 81.6%; p<0.001), had lower income, had more uninsured (9.6% vs 1.8%) and Medicaid (15.2% vs 9.6%) and fewer Medicare (40.3% vs 55.9%; p<0.001). Hispanics had better OS, with a median OS of 84.4 (95% CI 71.7-97.1) vs 70.5 months (95% CI 68.7-72.2; p<0.001). However, in the multivariable Cox model, Hispanic ethnicity was not associated with OS (HR 0.952, 95% CI 0.839-1.080; p=0.448). Conclusion This study is the first of its scale to demonstrate that female MCL patients have superior survival outcomes compared to males. It also demonstrated that neither Black race nor Hispanic ethnicity appears to be associated with worse survival outcomes. Despite its size, the NCDB is limited in the treatment information and disease characteristics it provides, including MIPI score, Ki-67, blastoid/pleomorphic morphology, and TP53 status. Thus, additional real-world dataset studies are needed to gain a deeper understanding of potential differences in sex, race and ethnicity with regards to disease characteristics and survival outcomes.

Background: Disseminated marginal zone lymphoma (MZL) is an indolent disease often observable at diagnosis with treatment indications similar to other indolent lymphomas. First-line therapy is typically rituximab alone or in combination with chemotherapy (e.g. bendamustine). Due to the long-life expectancy, avoiding alkylating agents to reduce bone marrow damage could be beneficial. In addition, a “chemotherapy free” option could have fewer and less severe complications. Bruton tyrosine kinase inhibitors (BTKi) are active and approved or NCCN-recommended beyond first line therapy in MZL. Moreover, BTKi are approved for first line therapy in Waldenstrom's Macroglobulinemia, a disease with both diagnostic and pathophysiologic overlap with MZL. We conducted a multicenter randomized trial of rituximab induction plus ibrutinib/placebo (RI vs RP) for patients with MZL in need of first line systemic therapy. Complete response (CR) rate at 30 months was the primary endpoint and progression free survival (PFS) was secondary. The target sample size was 63 in each arm. The study was closed after 22 eligible patients enrolled due to low accrual. Methods: Patients (pts) with either nodal, splenic or extranodal MZL were eligible. Prior surgery, radiation, antibiotic or antiviral therapy for MZL were allowed if followed by disease progression requiring treatment. Documented evidence of need for treatment included, but was not limited to, threatened end-organ function, bulky disease (>5 cm), symptoms, requirement for transfusion or growth factor support, or significant need for intervention. Transformation to DLBCL was excluded prior to entry including bone marrow assessment. Randomization occurred prior to rituximab weekly x 4 to either daily placebo (RP) or ibrutinib (RI) 560 mg starting on day 1 and continued until disease progression (PD), intolerance or CR at 30 months. Those with partial response (PR) or stable disease (SD) at 30 months could continue placebo or ibrutinib. CR assessment required both a negative FDG-PET and bone marrow biopsy. RESULTS: 22 pts enrolled (Feb 2020-March 2023) with baseline characteristics including: median age 67 years (35-78) and White race 17. Stage II (3), III/IV (17). Subtype: splenic 16, nodal 4, extranodal 2. Prior therapy: splenectomy 1, radiation 0, other surgery 0, antiviral/antibiotic 0. Median maximal tumor dimension was 3.7 cm (range 1.6-23.6); with >5 cm in 9 pts. Median time from diagnosis to treatment was 32 days (5-4712 with only 3 > 1 year). 11 pts were randomized to each arm. Responses: RP: 3 CR, 4 PR, 3 SD, 1 inevaluable; RI: 7 CR, 4 PR. No patient achieved CR30, but 3 had CR at 29 months: 2 RP, 1 RI. With a median follow up of 35 months (13-50), the median PFS by Log Rank was 14 mo (RP) vs 29 (RI), though this difference was not statistically significant in the setting of small numbers. Treatment was well tolerated. Only 1 pt experienced grade 3 events at least possibly related: hypoxia and dyspnea. This was attributed to COVID-19 and occurred on the RP arm. 1 CR patient with baseline clonal hematopoiesis developed myelodysplasia. Treatment improved baseline activities in 4/5 pts (1 RP, 3 RI). Baseline pain improved in 8 pt: 4 RP, 4 RI. All pts were alive at the data cuff off. Conclusions: This study is a chemotherapy free frontline trial in MZL and the first to utilize ibrutinib in frontline MZL. All pts received rituximab induction and were randomized at entry to RP vs RI. The COVID-19 pandemic affected site activation and accrual, ultimately contributing to low accrual and early study termination. Nonetheless, the results suggest a marked difference in median PFS favoring the RI arm, although small numbers preclude a statistically significant result. Notably, our results are qualitatively similar to those of Dimopoulos (NEJM, 2018) in Waldenstrom's Macroglobulinemia, a disease with similar characteristics to MZL. In that study, the median PFS by Log Rank was 20 months (RP) vs not reached (RI); and 30-month PFS 28% (RP) vs 82% (RI). (Hazard ratio for progression or death, 0.20; P<0.001). Further, our trial supports pursing a chemotherapy free first line approach in MZL.

Introduction: Kikuchi-Fujimoto disease (KFD), is a rare inflammatory disease of unknown etiology, typically presenting with transient fever and cervical lymphadenopathy. It is recently classified as a tumor-like lesion in the World Health Organization Classification 5th Edition. There are few large-scale studies on patient demographics and clinical course. This study aims to report detailed clinicopathological features of KFD. Methods: We reviewed 112 cases of KFD diagnosed at Okayama University Department of Pathology and Oncology, Okayama, Japan between 2012 and 2022. Patients who were diagnosed with autoimmune diseases or bacterial/tuberculous lymphadenitis after the initial presentation as KFD were excluded. Results: The average age of the included cases was 29.4 years (range:6 to 77 years) with slight female predominance (n = 51/115, 44.3% for male; n = 61/115, 53.0% for female). For the included cases of 30 years or older, there were more females than males. The cervical lymph nodes were the most commonly affected sites (85%). For the 70 patients who had complete follow-up data available in the electric medical records, the recurrence rate was 23%, without a difference between males and females. Laboratory tests demonstrated significantly lower complement 4 (C4) levels (p = 0.038) and a higher rate of positive antinuclear antibodies (p = 0.007) in the relapsed cases than in the cases without documented recurrence. The mean number of days prior to confirm the diagnosis was 71.5 days. Among the representative lymph node histology classification, proliferative type was the most common (n = 75; 77%), followed by necrotizing (n = 22; 22%), and xanthomatous (n = 1; 1%). The patients with necrotizing type had significantly enlarged lymph nodes (p = 0.047) and longer duration of symptoms (p = 0.009) compared to the proliferating type. Discussion: The present study provides data from a large KFD cohort to provide comprehensive clinicopathological information to date. While KFD is known to predominantly affect female, there were considerably more males up to age 30 than females, Being young and adolescent male KFD patients was associated with atypical features. Future studies are warranted to confirm the findings noted in the results, to clarify clinicopathological differences in the male young adolescent KFD, and further characterize the classical female KFD cases, including histological features, treatment responses, and association with autoimmune or malignant hematology conditions. Conclusion: In this study, we analyzed a large number of KFD cases and clarified characteristics. The comprehensive clinicopathological features provided by the present results may be useful in elucidating the pathogenesis and predicting the clinical course of such clinically challenging cases, including association with autoimmune diseases and its long-term outcomes.

Background: Due to recent advances, patients with follicular lymphoma (FL) have multiple treatment options with high response rates and durability. However, there is a gap in understanding how patient preferences influence treatment selection. To close this gap, we conducted a qualitative study using focus groups of adults with FL to understand their knowledge of treatment options, priorities, and decision-making process. We designed this study to inform the content of a planned discrete choice experiment in a larger population of patients with FL to better understand patient preferences and trade-offs around treatment delivery, side effects, outcomes, and quality of life. Methods: We conducted focus groups lasting 60-90 minutes, each with 3-5 participants recruited from the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study. The LEO Cohort Study is a multi-institutional prospective cohort study of newly diagnosed adults with non-Hodgkin lymphoma from July 2015 to present. Each focus group was co-led by two investigators (U.D. and M.T.) and conducted using Zoom video technology. Participants were asked to comment on their understanding about FL and available treatments, their ideal treatment, their decision-making process about prior therapies, and quality of life and side effects associated with treatment. We performed exploratory content analysis of participant understanding of FL and their treatment preferences. We will continue to conduct focus groups until we reach thematic saturation, which we anticipate will occur with one additional focus group. Themes from all focus groups were identified and agreed upon by both investigators (U.D. and M.T.) and were verified by additional investigators (J.D., M.L, M.H., B.K.L, C.C., M.M.). Results: To date, we conducted five focus groups with a total of N=21 participants (median age 60 [range 41-88], 66.7% female, 71.4% non-Hispanic White, 14.3% Hispanic, 9.5% Asian, 4.8% Black/Hispanic). We identified the following themes and representative quotes: 1) Holistic approach:Participants wanted their oncologists to view their care from a holistic perspective, discussing their individual priorities and options that would accommodate their fitness routine and ability to work. “[I wish] if doctors can consider not just the physical choices, but also the mental and emotional choices as well, the holistic person.” - Participant 13 “There's zero chance I can go back to working in the type of career where other people rely on me for things. I can't keep things straight.” - Participant 16 2) Ideal treatment:An ideal treatment would limit impact on fatigue, cognitive function, and have minimal toxicity to preserve quality of life and an active lifestyle. “I would say something that has minimal impact on daily life would be ideal and something that would make you feel better.” - Participant 6 3) Shared decision-making: Participants wanted to be better informed about available treatment options and often utilized second opinions to inform their decisions. “It helped to get the second opinion versus not. It would've been a completely different set of events.” - Participant 17 4) Treatment burden:Financial impact and effort required by patients to receive care (e.g., travel, number of office visits, and duration of therapy) were key factors in patient decision-making. “Part of my quality of life went down because I had to fight with my insurance company consistently, and we pay a lot of money.” - Participant 11 “Really explain the time options and calendarize the treatment and be more specific about the amount of time that you're going to spend at the hospital and the process.” - Participant 20 5) Representation: Minority participants raised concerns about not knowing if the available treatment data pertained to them. “[My end-goal would be] having an understanding of how the treatment is going to be for minority people. Many times the treatments are tested, they are not tested for minorities.” - Participant 21 Conclusions: The patient perspective is critical for treatment decision-making and education. People living with FL expressed a desire for a holistic and individualized approach to treatment decision-making that incorporated their lifestyle, minimized side effects, and limited overall treatment burden. These focus groups identified emerging themes that warrant further investigation for survivors with FL.

ABSTRACTDiffuse large B‐cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non‐PTR DLBCL. We found a significant increase in the frequency of TP53 (34% vs. 15%, p = 0.005) and ARID1A mutations (21% vs. 7%, p = 0.007) in PTR cases, with pathway analysis further demonstrating a downregulation of TP53 and an increase in chromatin modifying pathways. These results suggest that TP53 and ARID1A may be key mediators of PTR and important pathways contributing to the poor outcomes. We found that the current molecular classifiers were unable to identify PTR cases at diagnosis. However, our newly identified high‐risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.

Abstract Progression of disease within 24 months of initial immunochemotherapy (POD24) is a negative prognostic factor for patients with follicular lymphoma (FL). There is no standard treatment after POD24. Assembling an academic-based cohort from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence, we evaluated patterns of care and outcomes for 220 patients with FL with POD24 and retained FL histology. Therapy after POD24 was heterogeneous, with no treatment category accounting for >25% of the total. Among patients initially treated with bendamustine-rituximab, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was the predominant second-line choice (48%). Among patients initially treated with R-CHOP, aggressive salvage therapy was the predominant second-line choice (38%). Overall response rate to therapy after POD24 was 64% (95% confidence interval [CI], 56-70); complete response rate was 39% (95% CI, 32-46). The median event-free survival for therapy after POD24 was 9.8 months (95% CI, 7.3-12.1); 5-year overall survival (OS) was 71% (95% CI, 65-78). OS was inferior for patients aged >70 years (hazard ratio [HR], 2.31; 95% CI, 1.27-4.20) and those with high-risk FL International Prognostic Index scores at diagnosis (HR, 2.10; 95% CI, 1.23-3.60). No treatment category stood out with more favorable results. Cause of death was predominantly lymphoma related. Patients with follicular histology at their POD24 event had a low cumulative incidence of transformation (1.1% at 5 years). Our study is among the largest cohorts describing contemporary patterns of care for patients with POD24, providing a focused data set useful for interpreting and designing prospective clinical trials in this population.

Background: Major adverse cardiovascular events (MACE), including myocardial infarction, acute coronary syndrome, ischemic heart disease requiring revascularization, stroke, and heart failure, have been documented as significant contributors to mortality in cancer survivors. Coronary artery calcium (CAC) can predict MACE in non-cancer populations, while calcium in the aorta (CA) has not been evaluated as a prognostic marker. Every patient diagnosed with cancer undergoes a standard-of-care Positron Emission Tomography-Computed Tomography (PET-CT) or a chest CT before the initiation of chemotherapy. Hypothesis: To determine whether the CAC or CA of patients with Hodgkin's or non-Hodgkin's lymphoma, derived from standard-of-care PET-CT/chest CT, can predict the incidence of MACE. Methods: Patients treated with anthracycline-based chemotherapy, diagnosed and followed from January 1, 2013, through June 30, 2023, were included. Patients who did not undergo a PET-CT or CT, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CAC, CA, or CAC-CA was associated with the development of MACE. Calcium was retrospectively quantified using TeraRecon software (Durham NC) and categorized as: 0, 1-99, and >100. Outcome analyses was estimated using the Kaplan-Meier method. Results: 326 patients were included, mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was found in 89 patients and CA in 140. In the univariate regression model, a statistically significant association was found with values >100 for CA, CAC and CAC-CA with the risk of MACE. (Fig 1a/b/c). CAC equal to 0 demonstrated a significant protective effect against MACE. (Fig 1a). In the multivariable analysis, these associations persisted even after adjusting for comorbidities. (Table 1). Conclusion: CAC, CA and CAC/CA >100 in the standard-of-care CT/PET CT are predictors of MACE in lymphoma patients undergoing anthracycline treatment, a CAC equal to 0 has protective effect, these relationships remained statistically significant after adjusting for comorbidities.