Thompson, Carrie A.

Introduction: Assessing baseline cardiovascular (CV) risk factors is crucial for identifying cancer patients at higher risk of cardiotoxicity (CT). While both CT specific scores, including Heart Failure Association-International Cardio Oncology Society (HFA-ICOS) and our institutional score, as well as general CV scores like Atherosclerotic cardiovascular disease (ASCVD), have been used to assess CT risk; in lymphoma patients undergoing anthracycline therapy, their utility remains unknown. Aim: Evaluate the performance of each risk score to predict CT in a cohort of newly diagnosed lymphoma patients undergoing anthracycline treatment, followed for a median of 5.4 years. Methods: 326 Hodgkin and non-Hodgkin lymphoma patients treated and followed from 2013 to 2021 were prospectively assessed. Baseline measurements of the three risk scores were obtained. ASCVD score was not assessed in patients >80 or <40 years old or without baseline cholesterol. CT was defined during or after one year of chemotherapy as severe, moderate, or mild according to 2022 ESC guidelines. Logistic regression and AUC were used to assess the association of each score and compare the models. Results: Among 326 patients, 78 developed CT (8 severe, 21 moderate, 49 mild). A high-risk score from HFA-ICOS was significantly associated with severe and moderate CT(OR: 6.1, p=0.001), sensitivity 37%, and specificity 88%. A very high-risk classification of the institutional score was associated with severe and moderate CT (OR: 8.4, p=0.006), sensitivity 44%, and specificity 81%. No association was found between the ASCVD score stratification and CT. When mild CT was included in the analysis, the AUC values were lower (see Table 1). Conclusions: Cardio-oncology risk scores were associated with severe and moderate CT, outperforming ASCVD, but their predictive capacity was weak. Incorporating other serum or imaging biomarkers into the models may improve the predictive accuracy of CT risk assessment.

Background: Although marginal zone lymphoma (MZL) typically exhibits an indolent course, transformation to diffuse large B-cell lymphomas (DLBCL) is associated with a poorer outcome and remains a clinical challenge in managing patients with MZL. The limited existing literature reports various cumulative incidence rates, ranging from 2.5% and 4.7% (Finnish Cancer Registry, 1995-2018) to 6.6% and 8.4% (Florida Cancer Registry, 1995-2016) at 5 and 10-years, respectively, likely in part driven by varying study designs, ascertainment, and study population. Similarly, reported outcomes after transformed MZL (tMZL) have been variable. We evaluated the cumulative incidence of histological transformation (HT) to LBCL in a well-characterized prospective cohort of MZL patients from the upper Midwest, USA, and overall survival (OS) after transformation. Methods: Patients ≥ 18 years old with newly diagnosed MZL were prospectively enrolled in the University of Iowa/Mayo Clinic Molecular Epidemiology Resource (MER) cohort from 2002-2015. Clinical and treatment data were abstracted from medical records using a standard protocol. Patients were actively followed for retreatment, transformation, and death through 2022. Pathology was classified according to WHO 4/4R, including all transformations. The cumulative incidence of HT to LBCL was determined using death as a competing risk. Time to HT (TTHT) was defined as time from the date of MZL diagnosis to the date of transformation. We evaluated potential predictors of HT using a stepwise approach, and derived hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models. To assess predictors of OS after HT, patients ≥ 18 years old with newly diagnosed tMZL (into DLBCL) at Mayo Clinic between 1995 and 2002 (N=7) were combined with the MER cases. Results: We identified 524 patients with MZL in the MER cohort: 362 extranodal (EMZL; lung 18%, stomach 16%, orbit 13%, parotid 10%, skin 10%), 84 splenic (SMZL), and 78 nodal (NMZL). The median age at diagnosis was 63 years (range 18-92); 56% were female, and 83% were non-Hispanic white. During a median follow-up of 18.8 years (95% CI 16.7, NA), there were 25 HT (including 8 patients under observation) and 158 deaths. Eight Ten-year OS was 67% and 77% in the groups with and without HT, respectively. The overall cumulative incidence of HT was 1.5% at 2 years after diagnosis, 2.9% at 5 years, 4.5% at 10 years, and 5.7% at 15 years (Panel 1). The cumulative incidence of HT varied by subtype (e.g., at 5 years: 2%, 4% and 6%, in EMZL, NMZL and SMZL, respectively; Panel 2). The median time to HT also varied by subtype: 76 months (interquartile range (IQR) 43, 81) for EMZL, 30 months (IQR 16, 52) for SMZL, and 18 months (IQR 14, 23) for NMZL. In univariable analysis, predictors of HT were Stage III/IV (HR=3.4, 95% CI 1.36-8.53, p=0.009), elevated LDH (HR=2.98, 95% CI 1.25-7.12, p=0.014), and presence of ≥2 extranodal sites (HR=2.69, 95% CI 1.22-5.94, p=0.014). In multivariable analysis, elevated LDH was the only non-composite predictor of HT (HR=2.65, 95% CI 1.08-6.52, p=0.034). MALT-IPI score 2-3 (HR=3.61, 95% CI 1.06-12.25, p=0.040) and FLIPI score 3-5 (HR=2.19, 95% CI 1.22-8.22, p=0.018) also predicted HT. We analyzed OS after HT in 32 cases of tMZL (21 tEMZL, 7 tSMZL, 4 tNMZL). At HT, median age was 68 years (range 39-89); 24 (80%) patients presented with stage III/IV disease, 11 (58%) with elevated LDH, 12 (55%) with hemoglobin &lt;12g/dL, 3 (14%) with platelet count &lt;100x10 9/L and 9 (39%) with biopsy-proven bone marrow involvement. Twenty-six (81%) were treated with a systemic therapy, mainly CHOP-backbone therapy (R-CHOP n=13, CHOP n=4, R-EPOCH n=3, lenalidomide-R-CHOP n=1). Among these patients, the overall response rate was 85% (n=22/26). Three of the 4 non-responders died within 1 year. At last follow-up, 18/32 (56%) patients had died, and 6/13 (46%) alive patients had relapsed (MZL 3/6, DLBCL 3/6). After HT, 2-, 4- and 10-year OS were 76%, 55% and 55%, respectively. In univariable analysis, the only predictor of OS at HT was age ≥70 (HR 3.57 ,95% CI 1.34-9.48, p=0.011). Conclusion: In this North American prospective cohort of mainly non-Hispanic White patients, we found a low cumulative incidence of HT in MZL of 2.9% and 4.5% at 5- and 10-year, which was consistent with the Finnish findings (Kalashnikov et al., 2023). At HT, age was associated with OS and there was a high response rate to CHOP-backbone therapies.

Background: QOL can be affected by disease burden, side effects of treatment, and psychosocial effects of living with cancer. Although MZL is considered incurable, we previously found that patients diagnosed from 2002-2015 had a good QOL both at baseline (BL) and the first decade after diagnosis, regardless of treatment choice (Bommier et al., submitted). Here, we evaluate whether these findings can be extended to the 2015-2020 treatment era and a more diverse US cohort. Methods: Adults with newly diagnosed MZL from 8 academic centers were prospectively enrolled within 6 months of diagnosis from 2015-2020 in the LEO cohort (NCT02736357). Participants were actively followed for disease progression/relapse, retreatment and death. QOL was measured at BL, and at 1, 2, 3 and 5 years after diagnosis using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) scale (range 0-164), which consists of the FACT-General (FACT-G, range 0-104) plus a lymphoma-specific scale (range 0-60). Total FACT-G measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). We also used the Trial Outcome Index (TOI; range 0-112), which consists of FACT-G physical and functional WB plus the lymphoma-specific scale and is commonly used as an endpoint in treatment trials. All MZL patients with both BL and at least one follow-up QOL questionnaire were eligible for analysis. Patients were grouped by initial management: active surveillance (observation), local/antibiotic therapy (radiation, surgery, or anti- H. pylori therapy), or systemic therapy (chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and initial treatment groups were compared. Results: Of 384 patients, 60% were female, 91% were White, 6.6% were Black/African American, and 13% were Hispanic (all races). The median age was 64 years (range 19-94). For initial management, 28% (N=106) were observed, 31% (N=118) received local/antibiotic therapy, and 42% (N=160) received systemic therapy. Across treatment groups, there were no significant differences by age, gender, race, or performance status, while there were differences by Hispanic ethnicity (p=0.006), Ann Arbor stage (p&lt;0.001) and MALT-IPI score (p&lt;0.001) (Table). At BL, patients receiving systemic therapy had lower physical WB (p=0.008), emotional WB (p=0.04), functional WB (p=0.03), FACT-G total score (p=0.008), lymphoma subscale (p&lt;0.001), FACT-Lym (p=0.001) and TOI (p&lt;0.001) compared to observation and local/antibiotic therapy (Table). While FACT-G total scores were largely stable through 5 years after diagnosis, social/family WB declined from BL for patients initially receiving either local/antibiotic therapy (mean at 1-year -1.4, p&lt;0.05; 2-year -2.1, p&lt;0.05; 3-year -1.6, p&lt;0.05; 5-year-2.9, p&lt;0.05) or systemic therapy (mean at 2-year -1.2 , p&lt;0.05; 3-year -1.4, p&lt;0.05; and 5-year -1.2, p&lt;0.05), while this was stable for observed patients. In patients receiving initial systemic therapy, there was a transient improvement in the lymphoma-specific scale (mean +1.7, p&lt;0.05) and TOI (mean +3.7, p&lt;0.05). Otherwise, QOL remained stable over time and global QoL (FACT-G, FACT-Lym), TOI, Lymphoma-specific scale (Figure), and the other FACT-G subscales (physical, emotional, or functional WB) did not differ by initial treatment strategy. Conclusions: In the diverse LEO cohort from the recent treatment era, we confirm our prior findings for newly diagnosed MZL patients that QOL is globally stable over the first 5 years after diagnosis; emotional WB is not associated with initial treatment type, providing evidence that being initially observed does not negatively impact emotional health; and there is a decline in social/family WB (support from friends and family, family acceptance of illness, family communication, close to partner), which supports the need to consider interventions for patients to address these unmet needs. In addition, this study extends these findings to the lymphoma-specific scale, FACT-Lym, and TOI, which all showing largely stable trends in the 5 years after diagnosis and suggest that recent MZL treatment strategies, including systemic therapies, neither impair nor improve QOL.

Background: Helicobacter pylori (H. pylori) infection plays a critical role in the pathogenesis of gastric MALT lymphoma and its eradication can lead to tumor regression with a complete response (CR) rate of 78% in early-stage disease and a 5-year survival rate &gt; 95%. However, 10% of patients have gastric MALT lymphoma with no detectable H. pylori infection (Zullo et al., J Clin Gastroenterol 2010). There is controversy regarding whether H. pylori-negative gastric MALT patients should receive a trial of antibiotic therapy. The NCCN guideline recommends skipping antibiotics and proceeding directly to radiation therapy. On the other hand, the ESMO guideline recommends H. pylori eradication (HPE) as the first-line therapy for every patient with gastric MALT lymphoma irrespective of H. pylori status. This report aimed to evaluate the effectiveness of H. pylori eradication therapy in patients with limited-stage gastric MALT lymphoma. Methods: A retrospective analysis was performed to identify patients diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. H. pylori infection was determined by immunostaining of gastric mucosa, serology, stool antigen, or urea breath test. H. pylori status was considered positive when at least one of those tests showed positive results and negative when all of the performed test results in that patient were negative. The primary outcome was the CR rate defined as no macroscopic findings of lymphoma and negative biopsy resultsfrom the follow-up endoscopy 3-6 months following completion of treatment. Results: A total of 52 patients were identified; the median age was 68 years (range 52-87), and 29 (55.8%) were male. H. pylori infection was detected in 36.5% (19/52) patients by at least one of the methods - 14 cases by immunostaining, 3 cases by serology, and 1 each by stool antigen and urea breath test. The PCR or FISH for t(11;18) was performed in 10 cases (19.2%) and 2 cases of t(11;18) were detected (both were H. pylori-negative). All 19 H. pylori-positive patients were treated for H. pylori eradication (HPE) and 63% (12/19) achieved a CR. Of the 33 H. pylori-negative patients, 8 (24.2%) received HPE as the initial treatment and 1 (12.5%) responded with a CR. The treatment outcomes after HPE therapy showed the CR rate was significantly higher in H. pylori-positive patients than in H. pylori-negative patients (63.2% vs 12.5%, p=0.033) (Table 1). Only 2 of the 12 H. pylori-positive patients achieving CR have relapsed after a median follow-up of 89.7 months (range 2.9-227.8); the one H. pylori-negative patient that received HPE also remains in CR at 9+ months. The other first-line treatments applied for the 25 H. pylori-negative patients were radiation therapy in 18 (54.5%), single-agent rituximab in 3 (9.0%), surgical resections in 2 (6%), oral chlorambucil in 1 (3%), and observation in 1 (3%) The outcomes are shown in Figure 1. Conclusion: In our United States patient population, the incidence of H. pylori-negative gastric MALT lymphoma was 63%, much higher than previously reported (Zullo et al., J Clin Gastroenterol 2010) and similar to that found by other US investigators (Strati et al. 10.1002/ajh.25447). For limited-stage H. pylori-positive gastric MALT lymphoma, HPE is an effective first-line treatment and should be used. For patients who have no detectable H. pylori infection with multiple methods, the CR rate with HPE is very low in our experience. Although there is likely little harm to trying HPE (as ESMO guidelines suggest), this delays definitive radiation therapy. These data will be useful in patient counseling and treatment decision-making.

Background: Marginal Zone Lymphoma (MZL) is considered indolent but incurable, with a variety of initial treatment strategies including observation. Quality of life (QOL) can be affected by disease burden, side effects of treatment, and psychosocial effects of living with an incurable cancer. However, little is known about long-term QOL in patients with MZL. We investigated QOL at baseline (BL), and up to nine years after a diagnosis of MZL. Methods: Newly diagnosed MZL patients aged 18 years and older were prospectively enrolled within 9 months of diagnosis in the Iowa/Mayo Clinic Molecular Epidemiology Resource from 9/2002 - 6/2015. Pathology was reviewed by a hematopathologist. All MZL participants with both BL and at least one follow-up (FU) QOL questionnaire were eligible for this analysis. QOL was measured at BL and years 1-, 2-, 3-, 6- and 9-year FU with the Functional Assessment of Cancer Therapy-General (FACT-G) scale (range 0-108), which measures 4 QOL domains (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being (WB). Clinical data were abstracted according to a standard protocol and patients were systematically followed for events (progression, re-treatment, and death). Patients were grouped into initial management with active surveillance (observation), local/antibiotic therapy (including radiation, surgery, and anti- H. pylori therapy), or systemic therapy (including chemotherapy, targeted agents, or antibody therapy). Change in QOL scores over time was analyzed using mixed models for repeated measurements, and comparisons were made according to initial treatment group. Results: Of 324 participants in the analysis, 59% were female, 98% were White and the median age was 63 years. For initial management, 36% (N=118) were observed, 30% (N=96) received local/antibiotic therapy and 34% (N=110) received systemic therapy. Across the initial treatment groups, there were no statistically significant differences by age, gender, or performance status, while there were differences for Ann Arbor Stage IV (observation 50%, local/antibiotic 27%, systemic 67%, p&lt;0.001) and MALT-IPI score 2+ (observation 23%, local/antibiotic 18%, systemic 28%, p&lt;0.001). At BL, mean FACT-G total score was 85.7 (SD 13.1), and physical, social/family, emotional, and functional WB scores were 20.3 (SD 4.2), 24.4 (SD 3.9), 18.9 (SD 3.5), 22.1 (SD 5.3); these scores were similar across initial treatment groups (all p&gt;0.05). FACT-G total score was largely stable over time by treatment group (Panel 1). However, it declined at years 6 (mean -4.0, p&lt;0.05) and 9 (mean -3.7, p&lt;0.05) in the observation group (Panel 2), driven by a decline in functional WB, although this change was not significantly different from the other treatment groups. Further, in comparison with other treatment groups, local therapy was associated with a short-term 1-year improvement of FACT-G total score (mean +2.8, p=0.04), driven by improvements in both functional and emotional WB. For the subscales, we identified two major trends irrespective of treatment group: an overall improvement from BL of emotional WB at years 1 (mean +0.6, p&lt;0.05), 2 (mean +0.7, p&lt;0.05), 3 (+1.3, p&lt;0.05), 6 (+1, p&lt;0.05), and 9 (+1.3, p&lt;0.05) and an overall decline of social/family WB at years 1 (mean -1.1, p&lt;0.05), 2 (mean -1.7, p&lt;0.05), 3 (-2.1, p&lt;0.05), 6 (-2.7, p&lt;0.05), and 9 (-2.2, p&lt;0.05). There was no notable change from BL for physical or functional WB. Conclusions: This analysis is the first to provide prospective real-world QOL data on a longitudinal cohort of MZL patients with long follow-up. At BL, initial treatment was associated with stage and MALT-IPI score, but not QOL. Except for the transient 1-year QOL improvement in patients under local/antibiotic therapy, initial treatment groups had no impact on QOL over time. Irrespective of treatment group, emotional WB showed improvement over time, suggesting psychosocial adaptation by the patient, as it was found in aggressive lymphomas (Thompson et al., 2018). Further, emotional WB over time did not vary across treatment groups, suggesting that being initially observed did not lead to more emotional stress than being actively treated. Finally, decline in social/family WB (support from friends, family, family acceptance of illness, family communication, close to partner) suggests a need to consider interventions to patients and families to address these needs.

Introduction: The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past two decades, from finite duration chemoimmunotherapy (CIT) to an era of targeted agents such as Bruton Tyrosine Kinase (BTK) inhibitors, BCL2 inhibitors, and anti-CD20 monoclonal antibodies. Little is known about how initial management strategy (watch and wait [W&W] vs. treatment) at diagnosis impacts patient reported outcomes (PROs) in CLL survivors over time, particularly in light of therapeutic advances over the last decade. Methods: Newly diagnosed CLL patients were prospectively enrolled within 9 months of diagnosis in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER1) study between 9/1/02 and 6/30/15, and within 6 months of diagnosis in the MER Phase 2 (MER2) study between 7/1/15 and 5/1/20. PROs were measured using the Functional Assessment of Cancer Therapy-General scale (FACT-G), which generates Physical (PWB, range 0-28), Social/Family (SFWB, 0-28), Emotional (EWB, 0-24), and Functional Well-Being (FWB, 0-28) scores and a Total Score (0-108), with higher scores indicating better WB. In both cohorts, FACT-G was measured at enrollment and at years 1, 2, and 3 after diagnosis, while the timing of later assessments varied slightly by study (MER1: 6 yrs and 9 yrs; MER2: 5 years). We employed a generalized linear mixed model to evaluate change from baseline between groups with groups defined by each participant's initial management strategy (W&W vs. upfront systemic treatment). Initial management strategy was determined by the treating physician. The study was approved by the Mayo Clinic IRB. Results: A total of 722 patients were identified in MER1 and 256 patients in MER2. The median age at diagnosis was 63 years in MER1 and 66 years in MER2 (P&lt;0.05); 66% were male in MER1 and 68% were male in MER2 (P&gt;0.05). More patients initiated upfront systemic therapy in MER1 (n=380, 53%) than in MER2 (n=110, 43%). Other baseline clinical characteristics were similar between the cohorts ( Table 1). There was no statistical difference in the mean FACT-G total score at baseline between MER1 (85.0, SD 12.5) and MER2 (85.2, SD 12.7). In the MER1 cohort, statistically significant lower baseline QOL scores were observed in patients initiating upfront treatment compared to W&W on the FACT-G total score (P=0.002) as well as the PWB (P=0.01), EWB (P=0.03), and FWB (P=0.006) subscales. We also observed that over time, EWB and FWB scores were consistently lower amongst those treated upfront compared to W&W. Further, EWB scores steadily improved over time regardless of initial management ( Figure 1), whereas the FWB and PWB subscales were largely stable over time. Mean SFWB scores dropped amongst patients who received upfront therapy at 3 years, which then steadily improved through year 9 but did not recover back to baseline. SFWB scores were stable among W&W patients. In the MER2 cohort, no statistically significant differences in any of the baseline QOL scores were noted between the W&W vs. initial treatment groups. Despite this, we observed consistently lower mean EWB scores among patients who initiated upfront treatment compared to W&W pts over time. No other statistically significant differences in mean QOL scores over time were observed between groups. Similar to MER1, we did observe a drop in mean SFWB scores amongst patients initiating upfront therapy at 3 years of follow-up that remained decreased at year 5. Conclusion: This is the largest longitudinal study of CLL survivors that spanned over 18 years and two treatment eras. We demonstrated that in the novel treatment era, QOL metrics were similar between initial management strategies (W&W vs. treatment), suggesting that initial management had little to no impact on QOL at baseline or over time. In contrast, in the CIT era, we observed differences in QOL metrics at baseline between groups. In both treatment eras, patients with CLL who required upfront therapy demonstrated a decrease in SFWB from baseline at year 3 of follow-up, and the mean EWB scores were lowest at baseline regardless of initial management strategy (W&W vs. upfront treatment) or treatment era (CIT vs. novel agents), but steadily improved over time. These findings suggest opportunities for interventions to improve QOL in patients with CLL, and additional analyses are ongoing. Further follow-up in the era of novel agents is needed.

Background: Understanding the symptoms and quality of life (QOL) over time of adults with follicular lymphoma (FL) is important for treatment decision-making and clinical management. However, there are limited population-level data on the long-term QOL of adults with FL. We aim to describe the real-world, long-term QOL of adults with newly diagnosed FL up to 5/6 years after diagnosis. Methods: We used the Mayo Clinic/Iowa Molecular Epidemiology Resource (MER) and the multi-institutional Lymphoma Epidemiology of Outcomes (LEO) to identify adults with grade 1-3A FL who completed QOL surveys at baseline and follow-up. Participants with lymphoma were prospectively enrolled within 9 months of diagnosis in the MER cohort from 2002-2015 and within 6 months of diagnosis in the multi-institutional LEO cohort study across 8 cancer centers from 2015-2020. The LEO/MER cohort studies systematically collected information on disease status, QOL, health behaviors, and functional assessment. Treatments, disease relapses, and deaths were verified by medical record review. Treating physicians determined clinical management. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G) at years 1, 2, 3, and 5/6 post-diagnosis. A higher FACT-G total score (range 0-108) indicated better QOL across 4 subscales (range): physical (0-28), social/family (0-28), emotional (0-24), and functional (0-28) well-being. We categorized participants based on their frontline management at time of diagnosis: “observation” (surveillance), “treatment” (systemic treatment with immunotherapy +/- chemotherapy), and “local” (radiation) groups. We employed a generalized linear mixed model to evaluate and compare the changes in QOL scores (as a continuous variable) from baseline for the observation, treatment, and local groups, adjusting for sex, race/ethnicity, age, FLIPI risk, and cohort (i.e., LEO or MER). We also evaluated QOL changes by FLIPI risk. Results: Our study included 1,544 participants with FL and QOL data. At the time of enrollment, median age was 61 years (range 19-91), 88% were non-Hispanic White, and 49% were female. Based on initial management, 529 (34%) were in the observation group, 880 (57%) were in the treatment group, and 135 (9%) were in the local group. FLIPI risk was high for 17% in the observation group, 29.3% in the treatment group, and 3% in the local group. The mean (standard deviation) baseline FACT-G total score was lowest in the treatment group with the following baseline scores: 86 (13) for the observation group, 83 (14) for the treatment group, and 88 (12) for the local group (Table 1). The observation and local groups reported a greater worsening of their baseline FACT-G total score vs the treatment group at both the 2-year (-1.2, -0.8 vs +1.8, respectively) and 5/6 year (-5.4, -6 vs. -1.6, respectively) timepoints (Figure 1). This appeared to be driven by worsened physical and functional well-being in the observation (-1.3, -2.2, respectively) and local (-0.9, -2.4, respectively) groups vs the treatment group (0, -0.3, respectively). These differences were statistically significant between the observation vs treatment groups. There were no statistically significant differences in the other subscales, i.e., social/family and emotional well-being, by frontline management. Social/family well-being decreased across all groups by 5/6 years (-2.3 in observation, -2.2 in treatment, and -3 in local, p&lt;0.05). Regardless of FLIPI risk, the total FACT-G scores decreased within each FLIPI risk group at 5/6 years (-4.4 for low, -3.8 for intermediate, and -4.9 for high, p&lt;0.05). This was primarily due to worsened social/family well-being (-2.4 for low, -2.2 for intermediate, and -3 for high, p&lt;0.05) at 5/6 years. There was no statistically significant difference in QOL between FLIPI risk groups. Conclusion: This is one of the first and largest studies with real-world longitudinal QOL data for FL. Our study suggests that frontline systemic treatment initially improved QOL and resulted in a lower degree of QOL decline over time. Social/family well-being decreased over time regardless of frontline management or FLIPI risk. Further research is warranted to explore the impact of timing and specific systemic treatments on QOL, incorporate the patient/caregiver experience to address social/family well-being, and identify the clinical significance of our findings.

Background Central nervous system (CNS) involvement is a rare complication (&lt;5% of cases) of mantle cell lymphoma (MCL) and is associated with poor outcomes, highlighting the need for novel treatment approaches. We report the outcomes of a large cohort of patients (pts) with CNS MCL from Mayo Clinic and Memorial Sloan Kettering Cancer Center (MSKCC). Methods MCL pts with CNS involvement seen at Mayo Clinic and MSKCC between 1/2000-1/2021 were included. CNS involvement was defined by histologically confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS lymphoma. Medical records were reviewed for baseline characteristics, treatment, and outcomes. First-line MCL chemotherapy was categorized into higher intensity chemotherapy (i.e., anthracycline-based +/- high-dose cytarabine), moderate intensity chemotherapy (i.e., bendamustine-based regimens or single agent chemotherapy), and other. CNS treatment regimens were categorized as intrathecal (IT) therapy alone, systemic therapy (with CNS penetration such as IV cytarabine or IV methotrexate) with/without IT therapy, regimens with Bruton's tyrosine kinase inhibitors (BTKi), chimeric antigen receptor T cell (CAR-T) therapy, or radiation alone. Kaplan-Meier method was used for time to event analysis. Forest plots were developed using univariable Cox proportional hazards models. Results Seventy patients were included in the cohort, 34 from MSKCC and 36 from Mayo Clinic. Median age at MCL diagnosis was 65 years (range 56-72) and 52 were male (74%). MIPI score was available in 60 pts: low (n=10, 17%), intermediate (n=20, 33%), and high (n=30, 50%) risk. First line therapy included: higher intensity chemotherapy (n=42, 60%), moderate intensity chemotherapy (n=25, 36%) and other (n=3, 4%). Twenty-five (36%) pts underwent autologous hematopoietic cell transplantation in CR1. Median time from initial MCL diagnosis to CNS involvement was 24 months (m) (range 0-167). Four (6%) pts had CNS involvement at initial diagnosis. Abnormal CNS imaging was reported in 53 (76%) pts: leptomeningeal (n=37), leptomeningeal and parenchymal (n=4), parenchymal (n=8), orbital (n=4). The most common regimen following CNS diagnosis was systemic therapy with or without IT therapy (n=34, 54%) followed by treatment including BTKi (n=13, 21%), IT alone (n=10, 16%), radiation alone (n=3, 5%), and treatment including CAR-T (n=3, 5%). Three patients elected hospice care and four patients had missing/unknown CNS treatment. The overall CNS response to therapy was available in 54 patients: CR in 22 (41%) pts, PR in 8 (15%), SD in 11 (20%), and PD in 13 (24%) pts. Of the 70 patients, 63 died. Median follow up was 6.9 years (range: 1.6-11.2) from initial MCL diagnosis and 2.1 years from CNS diagnosis (range: 0.4-7.9). Median OS from MCL diagnosis was 3.4 years (95% CI: 2.4-4.6). In univariable Cox models, sex, stage, performance status, Ki67, or first line systemic chemotherapy type were not significantly associated with OS from MCL diagnosis. Low risk MIPI score (score &lt; 5.7) was associated with favorable OS (HR 0.31, 94% CI: 0.12-0.77; p value 0.01) compared to high risk. First-line treatment and treatment intensity were not associated with a significant difference in OS. Median PFS for the first CNS-directed therapy was 2.4 m (95% CI: 1.7-4.3). Cause of death was disease-related in a majority (n=49, 78%) of pts and therapy-related in 10% (n=6). The remaining 8 deaths had cause of death reported as missing or other (13%). Median OS from CNS involvement was 5.1 m (95% CI: 3.3-10.0) (Figure 1). When assessing OS from time of CNS diagnosis, treatment regimens incorporating BTK inhibitors were associated with a more favorable OS compared to systemic therapy +/- IT therapy (HR=0.37, 95% CI: 0.16-0.89, p value=0.03) (Figure 2). Conclusions Our dual center series confirms patients with CNS involvement by MCL have poor outcomes. When evaluating OS from the time of CNS diagnosis, novel therapies, including BTKi and CAR-T, may be more effective than CNS-penetrant chemotherapy for treatment of CNS relapse suggesting newer therapeutic approaches are required to improve outcomes.

Abstract Background The diagnosis of cardiotoxicity (CT) related to cancer therapy has gained significance due to its impact on morbidity and mortality. The 2022 cardio-oncology European Society of Cardiology (ESC) Guidelines defined CT as symptomatic if a patient has clinical heart failure or asymptomatic based on changes in the ejection fraction (EF) or global longitudinal strain (GLS). The role of right ventricular parameters, such as tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall strain (RVFWS), in predicting CT is unknown. AIM Evaluate if TAPSE and RVFWS can predict the development of CT in lymphoma patients treated with anthracyclines. Methods For this prospective observational study, Hodgkin & non-Hodgkin lymphoma patients (n=222) treated with anthracyclines were recruited from 2013 to 2021 and were followed for one year. Echocardiographic variables TAPSE and RVFWS were measured at baseline(T0), during treatment(T1), and up to 1 year after chemotherapy completion(T2). CT was defined according to the ESC guidelines excluding GLS changes. We performed: Kruskal-Wallis test to find differences at baseline values, logistic regression to evaluate the association of TAPSE and RVFWS with CT, area under the curve (AUC) of the receiving operator characteristic (ROC) to measure the discriminative test ability and two sample proportion test to calculate the negative predictive value (NPV). A p-value &lt;0.05 was considered significant. Results 222 patients were enrolled and 23 developed CT: 4.5% (n=10) at T1 and 6.2% (n=13) at T2. The median of RVFWS at T0 was significantly different in patients who developed CT compared to those who did not at T1 (CT-22% vs. no CT-27% p=0.04) and T2 (CT -23%, no CT -26.5% p=0.03). RVFW values at T0 were associated with CT at T1 (OR, 1.281 95% CI,1.09-1.52 p=0.002) and T2 (OR 1.23 95% CI,1.07-1.44 p=0.003). At T0 RVFWS cutoff value of -24% had an AUC of 0.85 for the prediction of CT at T1, with a sensitivity of 83% and specificity of 76% (p=0.03). At T0, RVFWS cutoff of -25% had an AUC of 0.80 for the prediction of CT at T2, with a sensitivity of 75% and specificity of 60%, (p=0.04). RVFWS absolute values &gt;26% at T0 and T1 had an NPV of 100% for the development of CT in T1 and T2. The median TAPSE at T0 was significantly different in patients who developed CT at T1 compared to those who did not (CT patients 18.7 mm vs no CT patients 23.6 mm p=0.04). TAPSE values at T0 were associated with CT development at T1 but not at T2 OR 0.76 (95% CI,0.66-0.87 p=&lt;0.001). At T0, TAPSE cutoff of 21.6 mm had an AUC of 0.77 for the prediction of CT at T1, with a sensitivity of 77% and specificity of 70% (p=0.03). Conclusions Baseline absolute RVFWS values &lt;24% and &lt;25% were associated with CT at T1 and T2, respectively. Values &gt;26% had an excellent NPV for the development of CT. Baseline TAPSE values &lt;21.6 were associated with CT at T1. These parameters should be evaluated in other cancer populations.TAPSE and RVFWS association with CTRVFWS and TAPSE at T0 to predict CT