Aggressive non-Hodgkin Lymphoma Research Articles

Bifunctional Inhibitor Reveals NEK2 as a Therapeutic Target and Regulator of Oncogenic Pathways in Lymphoma.

Expression of the serine/threonine kinase never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is essential for entry into mitosis via its role in facilitating centrosome separation. Its overactivity can lead to tumorigenesis and drug resistance through the activation of several oncogenic pathways, including AKT. Although the cancer-enabling activities of NEK2 are documented in many malignancies, including correlations with poor survival in myeloma, breast, and non-small cell lung cancer, little is known about the role of NEK2 in lymphoma. Here, in tumors from patients with diffuse large B-cell lymphoma (DLBCL), the most common, aggressive non-Hodgkin lymphoma, we found a high abundance of NEK2 mRNA and protein associated with an inferior overall survival. Using our recently developed NEK2 inhibitor, NBI-961, we discovered that DLBCL cell lines and patient-derived cells exhibit a dependency on NEK2 for their viability. This compromised cell fitness was directly attributable to efficient NEK2 inhibition and proteasomal degradation by NBI-961. In a subset of particularly sensitive DLBCL cells, NBI-961 induced G2/mitosis arrest and apoptosis. In contrast, an existing indirect NEK2 inhibitor, INH154, did not prevent NEK2 autophosphorylation, induce NEK2 proteasomal degradation, or affect cell viability. Global proteomics and phospho-proteomics revealed that NEK2 orchestrates cell-cycle and apoptotic pathways through regulation of both known and new signaling molecules. We show the loss of NEK2-sensitized DLBCL to the chemotherapy agents, doxorubicin and vincristine, and effectively suppressed tumor growth in mice. These studies establish the oncogenic activity of NEK2 in DLBCL and set the foundation for development of anti-NEK2 therapeutic strategies in this frequently refractory and relapse-prone cancer.

Hypofractionated Radiotherapy for Hematologic Malignancies during the COVID-19 Pandemic and Beyond.

Radiotherapy is integral in the management of hematological malignancies (HM). Standard radiotherapy dose fractionation regimens range between 20 and 50 Gy in 10-25 fractions over 2-5 weeks. This study presents the outcomes of patients with HM treated with hypofractionation radiotherapy (HFRT) during the COVID-19 pandemic. Patients (n = 36) were treated with HFRT between January 2020 and September 2022. The outcomes measured were the overall response rate (ORR), freedom from local progression (FFLP), and overall survival (OS). The median follow-up was 13.2 months. Thirty-three patients (92%) had non-Hodgkin (NHL) or Hodgkin lymphoma (HL). Eighteen patients (50%) had aggressive and nine (25%) had indolent NHL. Nineteen patients (53%) presented with stage I/II and fifteen (42%) with stage III/IV disease. Twenty-five (69.4%) and eleven (30%) received consolidative and definitive RT, respectively. Twenty patients (56%) received treatment to the neck and/or thorax and nine (25%) to the abdomen or pelvis. The total dose ranged from 18 to 42.5 Gy in 6-17 fractions/2.67-5 Gy per fraction. The median dose in 2 Gy fractions for an alpha/beta (α/β) ratio of 10 amounted to 39 Gy (SD ± 13.86) and 43.6 Gy (SD ± 12) for an α/β of 3. The most commonly used fractionation scheme was 39 Gy in 13 fractions. ORR was 94.4% for the entire cohort, and 100, 94.4, and 83.3% for indolent NHL, aggressive NHL, and HL patients. The two-year FFLP was 76% (95% CI: 34-93%) for the entire cohort and 100, 87 (95% CI: 56.4-96.5%), and 42% (95% CI: 1.1-84.3%) for the indolent NHL, aggressive NHL, and HL patients. Two-year OS for the entire cohort was 80% (95% CI: 59.9-90.5%) and 100, 66.1 (95% CI: 36.4-84.4%), and 100% for the indolent NHL, aggressive NHL, and HL patients. Only one patient presented with grade two pulmonary toxicity. HFRT in HM provides excellent local control to be validated in a larger prospective study.

SAMHD1 expression contributes to doxorubicin resistance and predicts survival outcomes in diffuse large B-cell lymphoma patients.

Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination. We evaluated the relationship of SAMHD1 levels with sensitivity to DSB-sensitizing agents in DLBCL cells and the association of SAMHD1 expression with clinical outcomes in 79 DLBCL patients treated with definitive therapy and an independent cohort dataset of 234 DLBCL patients. Low SAMHD1 expression, Vpx-mediated, or siRNA-mediated degradation/depletion in DLBCL cells was associated with greater sensitivity to doxorubicin and PARP inhibitors. On Kaplan-Meier log-rank survival analysis, low SAMHD1 expression was associated with improved overall survival (OS), which on subset analysis remained significant only in patients with advanced stage (III-IV) and moderate to high risk (2-5 International Prognostic Index (IPI)). The association of low SAMHD1 expression with improved OS remained significant on multivariate analysis independent of other adverse factors, including IPI, and was validated in an independent cohort. Our findings suggest that SAMHD1 expression mediates doxorubicin resistance and may be an important prognostic biomarker in advanced, higher-risk DLBCL patients.

Parotid Burkitt Lymphoma: Case Report

Salivary gland tumors are rare counting only 0.5% of all cancers, only 2% among them are lymphomas. Burkitt lymphomas is an aggressive mature non-Hodgkin B-cell lymphoma characterized by MYC oncogene activation, commonly occurring in nodal sites, however the extranodal sites are mostly seen in immunodeficiency associated Burkitt lymphoma as it is seen in patients with HIV infection. Clinically, the symptoms are related to the acute enlargement of gland due to the fast growing of the tumor and its rapid cells turnover. Diagnostic assessment requires biological investigations as well as cytological, histological and immunohistochemical exams to put out the diagnosis of Burkitt lymphoma. However, imaging is paramount by CT and MRI which finds its interest in its sensibility to characterize salivary gland tumors by the diffusion sequence and the estimation of apparent coefficient of diffusion. That being said, the diagnosis of parotid gland lymphoma is a differential diagnosis of parotid tumor because of its rarity. Our case is about a middle-aged woman suffering from a unilateral parotid swelling, its uncommon evolution pushed the investigations which leads to discovering a HIV infection, a diagnose the patient with a HIV-associated Burkitt lymphoma. We put the light on salivary gland location of this cancer by screening literature on this subject which benefitted from important advances of treatments, offering good outcomes in terms of freedom of event and overall survival.

Metabolic tumor volume and the survival of patients with Non-Hodgkin lymphoma treated with chimeric antigen receptor T cell therapy: a meta-analysis.

Chimeric antigen receptor T cell (CAR-T) is a promising treatment for aggressive Non-Hodgkin lymphoma (NHL). The aim of the meta-analysis was to determine the association between metabolic tumor volumes (MTV) derived on positron emission tomography before CAR-T infusion and the survival of patients with NHL. Relevant observational studies pertaining to the purpose of the meta-analysis were obtained through a search of PubMed, Web of Science, and Embase from inception of the databases to April 1, 2024. The data was combined using a random-effects model that accounted for the potential influence of between-study heterogeneity. Fifteen observational studies were included. Pooled results showed that compared to those with a lower MTV, the NHL patients with a higher MTV before CAR-T infusion were associated with a poor progression-free survival (hazard ratio [HR]: 1.73, 95% confidence interval [CI]: 1.48 to 2.02, p < 0.001; I2 = 20%) and overall survival (HR: 2.11, 95% CI: 1.54 to 2.89, p < 0.001; I2 = 58%). Subgroup analysis showed that the association between MTV and survival of NHL patients after CAR-T was not significantly impacted by study design, methods for determination of MTV cutoff, or analytic models (univariate or multivariate, p for each subgroup all < 0.05). Subgroup analysis suggested a stronger association between MTV and poor survival outcomes in patients with median of lines of previous treatment of 2 or 3 as compared to those of 4 (p for subgroup difference < 0.05). Further meta-regression analyses suggested that the association between MTV and survival was not significantly affected by sample size, age, proportion of men, cutoff value of MTV, follow-up duration, or study quality scores (p all > 0.05). A high MTV at baseline is associated with a poor survival of NHL patients after CAR-T. https://inplasy.com/, identifier INPLASY (INPLASY202450069).

Polatuzumab vedotin combined with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma: A systematic review protocol.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma subtype with a significant relapse rate and poor prognosis in relapsed/refractory (R/R) patients. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) has demonstrated promising efficacy and safety as salvage therapy for R/R DLBCL. This systematic review protocol aims to comprehensively evaluate the efficacy of Pola-BR for the treatment of R/R DLBCL by synthesizing data from relevant randomized controlled trials. This protocol details the eligibility criteria, search strategy, study selection, data extraction, and analysis methods for the systematic review. Randomized controlled trials comparing Pola-BR with other interventions for R/R DLBCL will be included. The primary endpoint is overall survival, with secondary endpoints being progression-free survival and incidence of adverse events. A comprehensive search will be conducted across databases such as Medline/PubMed, Cochrane Library, Web of Science, Scopus, EMBASE, ProQuest, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov from the January 2000 to April 2024. To assess the potential risk of bias, the Cochrane Risk of Bias 1 tool will be used. Data synthesis will utilize fixed-effect or random-effects models, and subgroup and meta-regression analyses will examine heterogeneity. Additionally, publication bias and sensitivity analyses will be performed, and the GRADE approach will be applied to assess the certainty of the evidence. This systematic review and meta-analysis protocol provides a rigorous framework for evaluating the efficacy of Pola-BR in the treatment of R/R DLBCL. The results will inform clinical decision-making and guideline development, addressing the unmet need for effective and tolerable treatments for this challenging patient population. Potential limitations and biases will be acknowledged, and future research directions will be discussed.

Utility of FDG-PET in predicting the histology of relapsed or refractory lymphoma

Abstract18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable prognostic tool in modern lymphoma care. In this study, we explored the use of quantitative FDG-PET parameters in predicting the histology of suspected relapsed or refractory (R/R) lymphoma. We retrospectively analyzed 290 FDG-PET scans performed for suspected R/R lymphoma. FDG-PET parameters measured were maximum and mean standardized uptake value (SUVMax and SUVMean), total metabolic tumor volume, and total lesion glycolysis (TLG). Receiver operating characteristic curve analysis was used to obtain the optimal thresholds that best discriminate (1) benign vs R/R lymphoma, (2) indolent vs aggressive non-Hodgkin lymphoma (NHL), and (3) aggressive transformation of indolent NHL. We found that although all 4 FDG-PET parameters discriminated R/R lymphoma from benign histology, TLG was the best performing parameter (optimal cut-off ≥245, sensitivity 63%, specificity 86%, positive predictive value [PPV] 97%, negative predictive value [NPV] 30%, area under the curve [AUC] 0.798, and P < .001). SUVMax discriminated aggressive from indolent NHL with modest accuracy (optimal threshold ≥15, sensitivity 46%, specificity 79%, PPV 82%, NPV 38%, AUC 0.638, and P < .001). In patients with a prior diagnosis of indolent NHL, SUVMax was a modest predictor of transformation (optimal cut-off ≥12, sensitivity 71%, specificity 61%, PPV 50%, NPV 78%, AUC 0.676, and P .006). Additionally, SUVMax ≥25 and an increase in SUVMax (ΔSUVMax) from baseline ≥150% were highly specific (96% and 94%, respectively). These FDG-PET thresholds can aid in identification of suspected R/R lymphoma cases with higher likelihood of R/R disease and aggressive transformation of indolent NHL, guiding the necessity and urgency of biopsy.

Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant

BackgroundThere is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT).MethodsPatients aged 0–39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed.ResultsTwo hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6–39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03).Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0–196.6) months after ASCT, and SPM was the cause of death in five (50%) of them.ConclusionsCAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.

The feasibility of a multidimensional intervention in lymphoma survivors with chronic fatigue

PurposeChronic fatigue (CF) affects 25–30% of lymphoma survivors, but interventions designed to reduce fatigue are lacking. The main aim of this study was to test the feasibility of a multidimensional intervention study in lymphoma survivors with CF. Secondary aims were to describe individual changes in fatigue, quality of life (QoL) and physical performance from pre (T0) to post (T1) intervention.MethodsThis feasibility study was as a one-armed intervention study performed in 2021. Hodgkin or aggressive non-Hodgkin lymphoma survivors received mailed study information and Chalder Fatigue Questionnaire and were asked to respond if they suffered from fatigue. The 12-week intervention included patient education, physical exercise, a cognitive behavioural therapy (CBT)-based group program and nutritional counselling. Feasibility data included patient recruitment, completion of assessments, adherence to the intervention and patient-reported experience measures. Participants responded to questionnaires and underwent physical tests at T0 and T1.ResultsSeven lymphoma survivors with CF were included. Of all assessments, 91% and 83% were completed at T0 and T1, respectively. Adherence to the interventional components varied from 69% to 91%. At T1, all participants rated exercise as useful, of whom five rated the CBT-based program and five rated individual nutritional counselling as useful. Five participants reported improved fatigue, QoL and physical performance.ConclusionLymphoma survivors with CF participating in a multidimensional intervention designed to reduce the level of fatigue showed high assessment completion rate and intervention adherence rate. Most of the participants evaluated the program as useful and improved their level of fatigue, QoL and physical performance after the intervention.Trial registrationClinicalTrials.gov, identifier: NCT04931407. Registered 16. April 2021-Retrospectively registered. https://www.clinicaltrials.gov/ct2/show/NCT04931407

Unraveling the enigma of B cells in diffuse large B-cell lymphoma: unveiling cancer stem cell-like B cell subpopulation at single-cell resolution.

Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of aggressive non-Hodgkin lymphoma. Despite receiving standard treatment, a subset of patients undergoes refractory or recurrent cases, wherein the involvement of cancer stem cells (CSCs) could be significant. We comprehensively characterized B cell subpopulations using single-cell RNA sequencing data from three DLBCL samples and one normal lymph tissue. The CopyKat R package was employed to assess the malignancy of B cell subpopulations based on chromosomal copy number variations. CIBERSORTx software was utilized to estimate the proportions of B cell subpopulations in 230 DLBCL tissues. Furthermore, we employed the pySCENIC to identify key transcription factors that regulate the functionality of B cell subpopulations. By employing CellphoneDB, we elucidated the interplay among tumor microenvironment components within the B cell subpopulations. Finally, we validated our findings through immunofluorescence experiments. Our analysis revealed a specific cancer stem cell-like B cell subpopulation exhibiting self-renewal and multilineage differentiation capabilities based on the exploration of B cell subpopulations in DLBCL and normal lymph tissues at the single-cell level. Notably, a high infiltration of cancer stem cell-like B cells correlated with a poor prognosis, potentially due to immune evasion mediated by low expression of major histocompatibility complex molecules. Furthermore, we identified key transcription factor regulatory networks regulated by HMGB3, SAP30, and E2F8, which likely played crucial roles in the functional characterization of the cancer stem cell-like B cell subpopulation. The existence of cancer stem cell-like B cells in DLBCL was validated through immunofluorescent staining. Finally, cell communication between B cells and tumor-infiltrating T cell subgroups provided further insights into the functional characterization of the cancer stem cell-like B cell subpopulation. Our research provides a systematic description of a specific cancer stem cell-like B cell subpopulation associated with a poor prognosis in DLBCL. This study enhances our understanding of CSCs and identifies potential therapeutic targets for refractory or recurrent DLBCL patients.

Impact of Modern Low Dose Involved Site Radiation Therapy on Normal Tissue Toxicity in Cervicothoracic Non-Hodgkin Lymphomas: A Biophysical Study.

This biophysical study aimed to determine fitting parameters for the Lyman-Kutcher-Burman (LKB) dose-response model for normal tissue complication probability (NTCP) calculations of acute side effects and to investigate the impact of reduced radiation doses on the probability of their occurrence in supradiaphragmatic non-Hodgkin lymphoma (NHL) irradiation. A cohort of 114 patients with NHL in the cervicothoracic region, treated between 2015 and 2021 at the University Hospitals of Münster, Hamburg, and Essen, with involved site radiation therapy (ISRT), were included. Among them, 68 patients with aggressive NHL (a-NHL) received consolidative radiation therapy with 24-54 Gy following (R-)CHOP chemotherapy. Additionally, 46 patients with indolent NHL (i-NHL) underwent radiotherapy with 22.5-45.0 Gy. Two treatment plans were prospectively created for each patient (a-NHL: 30.0/40.0 Gy; i-NHL: 24.0/30.0 Gy). NTCP were then calculated using the optimized LKB model. The adapted dose-response models properly predicted the patient's probability of developing acute side effects when receiving doses ≤ 50 Gy. In addition, it was shown that reduced radiation doses can influence the NTCP of acute side effects depending on the aggressiveness of NHL significantly. This study provided a foundation to prospectively assess the probability of adverse side effects among today's reduced radiation doses in the treatment of NHL.

Cerebrospinal fluid cytology-assisted diagnosis of T-lymphoblastic lymphoma: A case report

Background: Lymphoblastic lymphoma is a rare form of highly aggressive non-Hodgkin lymphoma. The most common clinical manifestations are superficial lymphadenopathy and mediastinal mass. In a few cases, invasion of the central nervous system is the first manifestation. It is also difficult to diagnose patients using the central nervous system as the first manifestation. Here, we report the case of a 26-year-old man with central nervous system disease as the primary manifestation; we used cerebrospinal fluid cytology (CSF-C) for early diagnosis and shared the importance of CSF-C for early diagnosis of T-cell lymphoblastic lymphoma. Case presentation: The patient was admitted to the hospital because of “right eyelid closure weakness with headache for 1 month and exacerbation with sluggish response for 1 week.” Physical examination revealed a bilateral Kernig sign (+) and Lasgue sign (+). The Mini-Mental State Examination and Montreal Cognitive Assessment scores were 20 (out of 30). When there was no abnormality in the imaging examination, the patient was misdiagnosed with meningoencephalitis and received anti-inflammatory treatment because the initial symptom was a clinical manifestation of the central nervous system, and the imaging and blood tests showed no definite abnormality. Cerebrospinal fluid has been studied and second-generation sequencing detection, such as after CSF-C tip to abnormal lymphocytes, to open the breakthrough of the diagnosis of lymphoma. Conclusions: In the cases with central nervous system injury as the first manifestation, CSF-C was combined with immunohistochemistry and cerebrospinal fluid flow cytometry to provide a clear and effective method and evidence for the early diagnosis of T-cell lymphoblastic lymphoma.

Ultra-Hypofractionated Involved Site Radiation Therapy (ISRT) As Salvage or Bridging Therapy in Aggressive Non-Hodgkin Lymphomas

Introduction: Conventional fractionated radiation treatment (RT) to a total dose of 40-50 Gy in 20-25 fractions is typically recommended in the ‘definitive’ intent treatment of aggressive chemorefractory non-Hodgkin lymphoma. However, during the time of COVID-19, recommendations for hypofractionated courses (5-13 fractions) arose (Yahalom et al Blood 2020) as modern radiation techniques should allow similar total doses to be delivered safely in far fewer fractions. Our aim is to evaluate the outcomes and toxicities of ultra-hypofractionated (&amp;lt;/=5 fractions) ‘definitive’ ISRT in aggressive non-Hodgkin lymphomas to see if this may be an acceptable alternate recommendation beyond COVID-19. Methods: We conducted an IRB-approved, retrospective review of all aggressive non-Hodgkin lymphoma patients treated at our institution with ‘definitive’ intent (40-50 Gy EQD2 with an α/β of 10) ultra-hypofractionated ISRT between April 2020 and July 2023. Demographic, disease-specific, and treatment-related variables were collected. Primary outcomes include objective response rate (ORR), defined as complete (CR) or partial response (PR) on post-RT positron emission tomography (PET) scans using the Lugano classification, local failure (LF), and radiation-related toxicity per CTCAE v5. Secondary outcomes include overall disease control and survival. Results: 26 ultra-hypofractionated radiation treatments were identified from 23 unique patients who were treated with ‘definitive’ intent ISRT (39.1% salvage, 30.4% early-salvage post CAR-T, and 30.4% bridging to SCT or CAR-T). The most common dose was 30 Gy in 5 fractions (96%); all patients were treated with IMRT with SBRT-type immobilization and image guidance as clinically indicated. The most common diagnosis was DLBCL (91%). 10/23 (43%) patients were female, the majority (82%) were ECOG 0-1 performance status, and the average age at time of RT was 68.9 years. 39% had all FDG-avid sites at the time of radiation treated. The median follow-up was 8.3 months (range 0.3-27.9 months). 26% of patients had acute radiation related toxicities, which were all grade 1-2 with the most common being fatigue (30%). There were no grade 3-4 toxicities, and no subacute or long-term toxicities. Initial local ORR was 20/21, or 95% (86% CR and 10% PR), while initial overall ORR was 12/21, or 57% (52% CR and 5% PR). At time of last follow up, only 1/24 (4%) of irradiated sites had local failure (2 data points N/A), with a TTLF of 1.5 months. 62% of patients had disease progression, with median time to disease progression of 1.5 months. At time of last follow up, 48% were dead, with a median time to death of 6.6 months. Conclusions: Ultra-hypofractionated ISRT in the ‘definitive’ intent treatment of aggressive non-Hodgkin lymphomas has excellent local tumor control and appears to be safe with minimal acute and subacute toxicities. In addition to patient convenience and cost effectiveness, short-course ISRT allows patients to quickly move on to next-line therapy when indicated. Prospective studies and long-term follow up are needed to further validate this as an alternative radiation treatment option.

Longitudinal Patient-Reported Outcomes and Clinical Outcomes By VES-13 and Comprehensive Geriatric Assessment in Older Adults with Aggressive Non-Hodgkin Lymphomas

Background: Older adults with aggressive non-Hodgkin lymphoma (NHL) can experience durable remissions with therapy but also substantial toxicities and healthcare utilization. The Vulnerable Elders Survey (VES-13) is a 13-item tool assessing age, self-rated health, and ability to perform physical and functional activities (score of 3+ indicates vulnerability). The Fondazione Italiana Linfomi comprehensive geriatric assessment (CGA) assesses age, comorbidities, and ability to perform physical and functional activities and classifies patients as fit, unfit, or frail. Both the VES-13 and CGA hold promise to risk stratify older adults for poor outcomes. Few data are available comparing these tools in assessing risk for poor survival and healthcare utilization, and prior studies have not examined the impact of therapy on longitudinal patient-reported outcomes (PROs). Methods: We conducted a longitudinal prospective study of 105 older adults with aggressive NHL at Massachusetts General Hospital or the Dana-Farber Cancer Institute between 9/2020 and 1/2023. Eligible patients were age &amp;gt;= 65 years at time of treatment initiation receiving combination chemoimmunotherapy. Patients could enroll up until cycle 1 day 8 of therapy. Patients completed questionnaires at baseline and 6 weeks, 12 weeks, 18 weeks, and 6 months post therapy initiation assessing demographics, quality of life (QOL-Functional Assessment of Cancer Therapy-Lymphoma [FACT-Lym]), depression and anxiety (Hospital Depression and Anxiety Scale [HADS]), and physical symptoms (Edmonton Symptom Assessment Scale-revised [ESAS-r]). At baseline patients also completed the VES-13 and underwent CGA evaluated by an oncologist. We utilized linear mixed models to examine longitudinal QOL, depression, anxiety, and physical symptoms. We assessed univariate factors associated with longitudinal QOL. Using Cox regression models controlling for gender, age-adjusted International Prognostic Index (IPI), hypoalbuminemia, Charlson comorbidity index (CCI), and lymphoma subtype, we assessed the relationship of VES-13 and CGA in separate models with overall survival (OS). We also examined factors associated with unplanned hospitalization within 6 months of therapy start using logistic regression. Results: We enrolled 106/163 (65.0%) patients. 1 patient was excluded due to treatment with an ineligible therapy. Patients had a median age of 73 years (range: 65-99, 38.1% &amp;gt;75, 21.9% &amp;gt;=80); most were male gender (64.8%), White race (96.2%), and married/with a life partner (72.4%). The most common lymphoma subtypes were DLBCL (73.0%), DLBCL/high grade B-cell lymphoma with MYC and BCL2 translocations (12.4%), and mantle cell lymphoma (10.5%). The majority (56/104, 53.8%) had an age-adjusted IPI of 2 or 3, over a third (34.3%) had a CCI score of 2+, and 82.9% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. 45.7% (48/105) had a VES-13 score of 3+. 40.0%, 9.5%, and 50.5% were fit, unfit, and frail, respectively, on CGA. QOL, depression, anxiety, and physical symptoms all improved over time (Figure 1). QOL improved regardless of age group, VES-13 category (&amp;lt;3 vs 3+), or CGA result (Figure 1). Compared to other patients, those 80+ years with either VES-13 score 3+ (β= -2.90, p=0.045) or frail on CGA (β= -3.68, p=0.007) had a worse QOL trajectory. Income &amp;gt; $50,000 annually (β=2.41; p=0.041) was associated with better QOL trajectory. VES-13 score of 3+ (HR=6.08; p=0.014) and frail on CGA (HR=5.20; p=0.028) were both associated with worse survival. Of those with follow up (N=66), 8 died within 1 year (1-year OS=87.9%), all of whom were both frail on CGA and had VES-13 score 3+. 25.8% (8/31) of the CGA frail patients and 28.6% (8/28) of those with VES-13 3+ died within 1 year. VES-13 score (OR=1.16, p=0.028) was associated with greater likelihood of unplanned hospitalization. Conclusion: Older adults with aggressive NHL often experience improvement in QOL and other PROs with treatment, even across age and frailty categories. VES-13 score and CGA identify patient groups at high risk for early death and poor QOL trajectory, for whom novel therapies and supportive care interventions are warranted. Higher VES-13 score is also associated with higher risk of unplanned hospitalization. Routine assessment of VES-13 and CGA has high potential for early identification of high risk patients and implementation of appropriate interventions.

CAR T Cell Exhaustion but Not Ex Vivo Cytotoxicity Is Predictive of Patient Clinical Response: An Interim Analysis of ACIT001/EXC002, a Phase Ib/II Trial of Decentralized Production of CAR T Cells for Treatment of Relapsed/Refractory Aggressive NHL and ALL

Chimeric antigen receptor (CAR) T cell therapy is an increasingly prominent form of next-generation immunotherapy in both hematologic and solid tumor malignancies. Multiple CAR T products have received regulatory approval for use as treatment in relapsed and refractory leukemias and lymphomas. However, approximately half of these patients do not respond to therapy and production of CAR T cells is a difficult, expensive, and time-consuming process. Although much has been learned about the fundamental biology of CAR T cells over the past decade, we are still unable to accurately predict which patients will respond to therapy. In particular, few studies have specifically examined biological characteristics of manufactured CAR T cells and correlated these to relevant clinical outcomes. In this study, we analyzed the lymphocyte populations and CAR T cells from patients enrolled in ACIT001/EXC002, a Canadian multi-centre phase Ib/II single-arm clinical trial of decentralized production of second-generation CD19/41BB/CD3z CAR T cells for treatment of multiply relapsed/refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). CD3-positive T cells and CAR T products were comprehensively immunophenotyped by flow cytometry. Thecapacity for manufactured CAR T cells to kill tumor cells was assessed using an ex vivo cytotoxicity assay. CAR T cell immunophenotype and cytotoxic potential were correlated with clinical outcomes including response to therapy, progress-free survival (PFS) and incidence of serious adverse events. To date, 23 patients have been enrolled, of which 16 had an aggressive NHL while the remaining 7 had been diagnosed with B cell ALL. Mean age of participants at time of enrollment was 57 (range: 26-77) and 65.2% were male. CAR T product was manufactured using lentiviral transduction with a median transduction efficiency of 32.1% (range: 9.1% to 55.5%). A majority of patients achieved a complete response as evaluated by PET scan on day 28 post-CAR T cell infusion with only 3 patients showing disease progression, 1 patient achieving only partial response, and 3 patients being unevaluable. We were able to evaluate PFS at 6 months in 15 out of 23 patients, with 46.7% of patients experiencing progression and/or mortality within this period. Surprisingly, while CAR T cell cytotoxicity ex vivo trended higher in patients that achieved a complete metabolic response compared to those with partial response or disease progression, this did not reach statistical significance (p = 0.280). However, expression of T cell exhaustion markers such as PD-1 CAR T products was found to be significantly increased in non-responders (p = 0.010). Higher expression of exhaustion markers was also found to be associated with decreased CAR T persistence in vivo as measured by circulating CAR T cell levels at day 14 post-infusion. In our study cohort, CAR T products had either similar or significantly greater proportions of CD4+ as compared to CD8+ T cells. CAR T cells were found to express high levels of HLA-DR and CD127, however this did not correlate with cytotoxicity, response to therapy or PFS. Patient CAR T cells, regardless of the level of exhaustion marker expression, tended to be highly skewed towards the T effector memory subset, with almost no populations of naïve or memory T cells identified. In this analysis of the impact of biological characteristics of CAR T cell products on patient outcomes, we found that CAR T cell exhaustion rather than cytotoxic activity is correlated with response to treatment and higher PFS at 6 months. Interestingly, the degree of patient T cell exhaustion had an impact on transduction efficiency but not the cytotoxic potential of the manufactured CAR T cell product. Taken together, our data indicate that CAR T cell exhaustion and persistence following infusion rather than cytotoxic potential is a key predictor for patient response to treatment. While our conclusions are currently limited by small sample size, more patients are presently being accrued to allow for more robust analysis in the future.

A National Cancer Database Analysis of Demographics, Treatment Patterns and Survival Trends of Patients with Plasmablastic Lymphoma in US: Does Ethnicity Predict Enhanced Outcomes?

Background: Plasmablastic lymphoma (PbL) is an exceedingly rare, aggressive non-Hodgkin lymphoma with overlapping features of myeloma and lymphoma diagnosed most commonly in immunocompromised individuals, especially in the setting of human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection ( Int J Lab Hematol PMID 36074710). Pathologically, it is characterized by lacking CD20 and PAX5 expression with the presence of CD38, CD138, MUM1/IRF4, Blimp1, and XBP1 expression ( Blood Lymphat Cancer PMID 31360094). There is no established standard of care ( Blood PMID 25636338). Due to the disease's rarity, limited information is available on PbL, especially when focusing on underrepresented minorities. This study aims to describe the demographics, treatment patterns, and survival outcome differences in Hispanic (HI) versus non-Hispanic (NH) patients in the United States with PbL. Methods: Data was analyzed on patients with PbL in the US reported to the NCDB between 2010 and 2019. Sociodemographic and treatment characteristics were compared between ethnic groups. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) between HI and NH populations. Multivariate analysis and propensity score matching were performed with adjustment for age, stage, co-morbidity score, insurance status, type of facility and great circle distance. Results: Between 2010 and 2019, 1624 patients were diagnosed with PbL with 16% identified as HI. HI were diagnosed at a younger median age of 48 years as compared to NH at 58 years. Diagnosis was made predominately in males (78%) with no statistical difference between HI and NH. Most HI and NH were white (92% and 74% in HI and NH, respectively) with increased racial diversity among NH. 17% of all patients identified as black with 1% HI and 21% NH. Regarding income, 32% HI had an income less than $38,000 versus 23% NH; whereas, 31% NH had an income greater than $63,000 versus 20% HI [p=0.017]. 38% HI had a Charlson-Deyo Comorbidity Index score ≥ 2 as compared to 27% NH [p&amp;lt;0.001]. Table 1 provides additional information on demographics. 45% of all patients had stage IV disease at the time of diagnosis. 86% of all patients received treatment with no statistical difference among HI and NH [p=0.246]. 67% of HI were treated at academic/research programs compared to 50% of NH [p=0.004]. The median distance between the patient's residence and treatment facility was 6.9 miles for HI versus 9.8 miles for NH [p=0.001]. The survival probability at 2, 5, and 10 years for HI was 59%, 52%, and 42%, respectively as compared to NH was 47%, 37%, and 31%, respectively. The median survival time (MS) was 9.4 years in HI versus 1.4 years in NH [p &amp;lt;0.001]. Figure 1 shows the Kaplan Meier curve comparing overall survival (OS) between HI versus NH.When adjusted on multivariate analysis, there were no independent variables associated with better or worse OS; moreover, propensity matched analysis showed no MS difference between HI vs NH (1.79 years versus 1.17 years). Conclusion: This hospital-based analysis noted that HI presented with PbL at a younger age than NH; however, HI more frequently had a higher Charlson-Deyo Comorbidity Index score than NH. There was no statistical difference in the stage at diagnosis between HI and NH. Additionally, HI had a lower income and no medical insurance as compared to NH suggesting HI possibly had inferior access to medical resources. Paradoxically, HI had significantly higher OS rates. Further insight into the disease's intrinsic characteristics, as well as biological factors, is needed to gain a better understanding of these poor outcomes.

Prephase Cyclophosphamide: An Advantageous Bridge to Definitive Therapy

Background Classic Hodgkin lymphoma (cHL) and aggressive non-Hodgkin lymphoma (NHL) account for an estimated 0.5% and 4.1% of all new cancer diagnosis in the US in 2023, respectively. At time of diagnosis, approximately 43% of cHL and 53% of NHL are staged as advanced disease (stage III-IV). While these diseases are considered curable, standard treatments involve intensive combination chemotherapy that may preclude certain patients from receiving optimal therapy. One option to minimize risks is to use prephase cyclophosphamide (pCy) as an initial treatment in aggressive lymphomas. There is however limited data on the utility, adverse effects, and outcomes of this approach. Here we present data on our institutional experience of employing pCy for patients ineligible for intensive chemotherapy. Methods We performed a single institution, retrospective chart review of patients with history of cHL and NHL that received cyclophosphamide (Cy) as an initial chemotherapy during hospitalization. Lymphoma subtype, medical history, baseline bloodwork at time of treatment initiation, outcomes including transplant, relapse data and overall survival were collected. Fifty patients received pCy at 200 mg/m2 with the remaining four receiving 100 mg/m2, 150 mg/m2, or 300 mg/m2 based on provider preference. Corticosteroids, including prednisone, dexamethasone or methylprednisolone, were administered simultaneously with varying duration and dosage. We analyzed hepatic and kidney injury at the time of diagnosis, after initiation of pCy and time to recovery. Acute kidney injury (AKI) was defined as an increase in creatine more than 30% from baseline and hepatic injury was defined based on Common Terminology Criteria for Adverse Events (CTCEA) version 5. Charlson scores for all patients were collected. Results Fifty-four patients received pCy as a bridge to possible definitive therapy. The most common diagnosis was diffuse large B-cell lymphoma (DLBCL) and cHL, with 29 (53.7%) and seven (13%) patients, respectively (Figure 1). The median age was 56 years (18-84) with 21 (39%) patients &amp;gt;65 years. Advanced stage was observed in 49 (90.7%) patients. Four patients required treatment for tumor lysis syndrome (TLS) prior to initiation of pCy. Nineteen (35%) patients had AKI and 15 (28%) patients had hepatic injury at the time of initial presentation. Five patients experienced AKI from pCy with an average time to recovery of 11.2 days. Six patients, with only two having concurrent AKI, had hepatic injury from pCy with an average time to recovery of 8.5 days. PCy allowed 42 (78%) patients to undergo definitive treatment in respect to their lymphoma subtype. Eight (14.8%) patients went on to receive a consolidative autologous transplantation (HSCT) after reaching a remission from definitive therapy. At the time of our analysis, 30 (55%) patients are deceased which includes four patients that underwent HSCT. Of the 30 deceased, 10 patients were transitioned to comfort care during the admission after receiving pCy. Median overall survival is 370.5 days. Conclusion Based on our institutional experience, pCy is a reliable method to salvage patients with aggressive lymphomas that are not candidates for intensive chemotherapy. In our analysis, pCy allowed 78% of patients to receive definitive therapy for their respective lymphoma. In general, patients receiving pCy required hospitalization related to disease burden and pCy represents an effective and cost-efficient bridging strategy to outpatient treatment. Cyclophosphamide has a broad indication across hematologic malignancies and is a well-tolerated chemotherapy with a limited side effect profile. The modest dosing in combination with corticosteroids allows initial disease control and provides the ability to start definitive therapy in a timely manner. Additionally, we feel that pCy should be considered when designing clinical trials in an effort to promote enrollment of the “real-world” patient.

Baseline CD4 T Cells Are Associated with Improved Response to CD20-CD3 Bispecifics in Lymphoma

Background: Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. Mosun is approved for the treatment of patients (pts) with relapsed/refractory follicular lymphoma (FL) after two or more systemic therapies and has shown activity in both aggressive non-Hodgkin lymphoma (aNHL) and indolent (iNHL). Previous reports have shown that CD20 loss is a common mechanism of resistance to Mosun (Schuster SJ, ASCO 2022). However, as the mechanism of action of Mosun is T cell mediated killing of tumor cells, we sought to characterize the immune microenvironment of tumor samples from patients with NHL treated with Mosun. Here we report integrated biomarker analysis of pt samples from the phase I/II Mosun monotherapy trial (NCT02500407). Methods: Baseline and at-progression biopsies were collected from 240 relapsed/refractory NHL pts from the fixed dosing (arm A) and Cycle 1 step-up dosing (arm B) cohorts, including 78 DLBCL, 89 FL, 37 transformed FL (trFL), and 36 other aNHL and iNHL histologies (including MCL, MZL, SLL, &amp; RS). A total of 265 biopsies were profiled via RNASeq, including 58 paired baseline and at-progression samples. As a proxy for immune subset prevalence, immune gene signatures were calculated using principal component analysis. Association with best overall response was calculated using limma with histology and archival status included as covariates for the pooled cross-histology analysis, or with archival status for within-histology comparisons. Significance for exploratory analysis was defined as false-discovery rate (FDR)&amp;lt;0.05. Results: Pooled analysis of all baseline biopsies identified expression of 76 genes as significantly associated with response (Figure 1A). A number of immune-related genes, such as ITGAL, IL6R, and TOX2 were expressed at higher levels in responders. Gene signature analysis revealed that most of the top hits were T cell related, with T follicular helper (Tfh) signatures most strongly associated with response. Analysis of individual histologies revealed that the majority of genes identified had indication-specific associations, with significant hits in DLBCL (n=472) or trFL (n=4). No hits were found in FL after FDR correction. DLBCL hits appeared mostly tumor-specific (HLA-E, DOK1, and ITGA2), while trFL hits were more associated with CD4 T cell biology (TIGIT and FOXN3). The Tfh signature was the most strongly associated with response in trFL, and was also nominally significant in FL (Figure 1B). The signature displayed a histology-specific expression profile, with lower expression in aNHL and higher expression in iNHL. A split was observed in trFL, with responders showing signature scores similar to iNHL and non-responders like aNHL. Other CD4-but not CD8-signatures showed a similar profile. At progression, a small number of genes showed sustained changes, with reductions in XCR1 &amp; CLEC9A, and induction of ALOX15B seen in patients up to 2 years after the last Mosun administration, suggesting long-term changes in the immune microenvironment during the development of resistance. Conclusions: Baseline biomarker data reveal an important role for CD4 T cells in Mosun response and suggest that higher prevalence of CD4s may be a factor in the improved response to Mosun in indolent NHL. Our data specifically point to Tfh cells as potential drivers of response, although the mechanisms by which Tfh contributes to response, as well as the implications for other bispecifics, requires more exploration.

Isatuximab and Cemiplimab in Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Multi-Center, Open-Labeled Phase II Study (CISL2102/ICING study)

Introduction Extranodal NK/T-cell lymphoma (ENKTL), an Epstein-Barr virus (EBV) associated lymphoid malignancy is a rare but aggressive non-Hodgkin lymphoma (NHL). The prognoses of patients with relapsed or refractory (R/R) ENKTL are still poor because there is limited treatment option for R/R ENKTL. The expression of PD-L1 (Programmed Death Ligand-1) is common in ENKTL because EBV could induce the PD-L1 expression. Thus, PD1 and PD-L1 inhibitors have been tried as salvage treatments, but their single-agent activities in previous studies were not satisfactory. CD38 has been considered as another potential therapeutic target in ENKTL because tumor cells of ENKTL could express CD38. CD38 expression was also reported to be related with the resistance to PD1 inhibitors. Thus, we conducted a phase II study with the combination of cemiplimab (PD1 inhibitor) and isatuximab (monoclonal anti-CD38 antibody) in patients with R/R ENKTL. Methods We aimed to analyze the efficacy of isatuximab (anti-CD38 monoclonal antibody) and cemiplimab (anti-PD1 monoclonal antibody) in patients with R/R ENKTL. Patients eligible for this study had relapsed or refractory disease at least one line of treatment. The induction treatment consisted of cemiplimab 250mg (day 1 and 15) and isatuximab 10mg/kg (day 2 and 16) intravenous administration every 4 weeks for 6 cycles. After that, responders received cemiplimab 250mg and isatuximab 10mg/kg once every 3 weeks up to 24 months or until progression, death, or study withdrawal. The primary end point was complete response (CR) rate and secondary end points were objective response rate (ORR) consisting of CR and partial response (PR), progression-free survival (PFS), and safety. The target CR rate was designated as 40% (P1). Considering 20% (P0) of CR rate after conventional salvage therapies and 10% of drop-out rate, 37 patients were planned to be enrolled. Results Between June 2021 and May 2023, we enrolled 37 patients. At enrollment, 29 (78%) patients had stage IV disease and 26 (70%) belonged to the high-risk of prognostic index of NK lymphoma (PINK-E, Table 1). Prior to the participating in the study, 19 (51%) patients had received ≥ 2 lines of systemic therapy. At the time of enrollment, 10 (27%) patients were refractory to their previous treatments whereas the remaining patients had relapsed diseases. After the first day of first cycle, all patients completed at least one cycle of treatment. The response rate was determined by the best response during treatment. As 16 patients achieved CR, the CR rate was 43% (16/37). Thus, the primary end point was met in the study. The ORR was 65% (24/37) consisting of 16 CR and 8 PR. The responders could maintain their treatments up to 32 cycles, and the median PFS of responders was 21.0 months (95% CI: 7.8-34.2 months, Figure 1). The comparison of characteristics between responders and non-responders showed stage at enrollment was significantly associated with response (P = 0.032, Table 1). Thus, eight patients with stage I/II at enrollment responded to the treatment (100%, 8/8) whereas 55% (16/29) patients in stage III/IV responded to the treatment. The risk of PINK-E and other unfavorable parameters were not related with treatment response. Furthermore, the PD-L1 expression showed an association with response (Table 1), thus, 83% of patients (15/18) achieved CR or PR. Most treatment-emergent adverse events were grade 1-2 in severity. Only one patient with CR withdrew from the study due to neuropathic pain that was related with the patient's previous treatments. The hematologic and non-hematologic grade ≥ 3 events were reported in 12 (32%) patients including pneumonia. However, they were manageable, and there was no treatment-related death. Conclusions The combination of isatuximab with cemiplimab showed durable antitumor activity and manageable safety profiles in R/R ENKTL. Especially, patients with PD-L1 expression showed better outcomes than patients with low PD-L1 expression. Further study with a larger study population should be warranted to confirm our findings.

Prognostic Understanding in Newly Diagnosed Older Adults with Diffuse Large B Cell Lymphoma (DLBCL) or DLBCL/High Grade B-Cell Lymphoma with MYC and BCL2 rearrangements

Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive lymphoid malignancy that often affects older adults. Therapy is potentially curative, with up to two-thirds of patients cured with chemoimmunotherapy but carries substantial risk of toxicity. Treatment of older adults must balance the potential for cure with the risk of therapy toxicity and intensive healthcare utilization. Therefore, prognostic understanding is a crucial component of informed decision-making for this patient population. Yet, data regarding prognostic understanding in older adults with DLBCL are lacking. Methods: We conducted a prospective study of older adults with aggressive non-Hodgkin lymphomas at two tertiary care hospitals between 9/2020 and 01/2023. Eligible patients were age &amp;gt;= 65 years at time of treatment initiation receiving a combination chemoimmunotherapy. Patients could enroll up until cycle 1 day 8 of therapy. Patients completed questionnaires at baseline that assessed demographics as well as information preferences and prognostic understanding (Prognosis and Treatment Perception Questionnaire) and underwent a comprehensive geriatric assessment. We used descriptive statistics to examine patient beliefs regarding likelihood of cure, the importance of knowing about prognosis, and preferences for information about treatment at baseline. We focused on the subset of patients (N=92) with DLBCL or DLBCL/high grade B-cell lymphoma with MYC and BCL2 translocations (double hit lymphoma) in order to have a relatively homogenous population for prognosis and likelihood of cure. Results: The parent study enrolled 106/163 (65.0%) patients, with 92 patients having DLBCL or double hit lymphoma. 88/92 enrolled patients with DLBCL (95.7%) submitted the prognostic understanding questionnaire. Among DLBCL/double hit lymphoma patients (N=92), the median age was 74 years (range: 66-99), and most were male gender (63%), White race (96.7%), and married/with a life partner (73.9%). 48/91 (52.7%) had an age-adjusted International Prognostic Index of 2 or 3, 30/92 (32.6%) had a Charlson comorbidity index of 2+ (not counting the patients' lymphoma), 14/92 (15.2%) had an Eastern Cooperative Group performance status of 2-4, and 50% (46/92) were frail based on comprehensive geriatric assessment. When asked about their likelihood of cure, 37.5% (33/88) selected &amp;gt;90% chance, 37.5% (33/88) selected 75-90% chance, 20.5% (18/88) selected 50-74% chance, 3.4% (3/88) selected 25-49% chance, and 1.1% (1/88) selected 10-24% chance of cure. Most (88.6%;78/88) patients believed that the primary goal of their current treatment was to cure their cancer, and most (93%; 80/86) believed that was their oncologist's primary goal. When asked if they would prefer a course of treatment focused on extending life as much as possible even if it meant more pain and discomfort versus a plan of care focused on relieving pain and discomfort as much as possible, even if it meant not living as long, 30.0% (26/88) chose extending life as much as possible, 40.9% (36/88) chose relieving pain as much as possible, and 30.0% (26/88) did not know. 94.0% (78/83) reported that they had a conversation about prognosis with their oncologist. The majority (91%; 78/86) felt it was extremely important or very important to know about their prognosis over time, and felt (81.4%; 70/86) they had just the right amount of information about their prognosis. Patients stated that knowing about their prognosis was extremely helpful in making decisions about treatment (75.3%; 61/81), preparing for the future (68.3%; 56/82), maintaining hope (79.3%; 65/82), and coping with the disease (72.5%; 58/80). 74.4% (61/82) said that overall knowing about prognosis was extremely helpful. Conclusion: In this cohort of older adults receiving treatment for DLBCL or double hit lymphoma, the vast majority felt it was important to know prognostic information over time and found that this information was helpful for decision making. Our finding that the majority estimated their likelihood of cure to exceed 75% despite most having aa-IPI scores indicating average cure rates &amp;lt; 60 suggests that older adults with newly diagnosed DLBCL hold overly optimistic views of their prognosis.