Large B-cell non-Hodgkin Lymphoma Research Articles

Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome with Toxic Epidermal Necrolysis: Overlap in an HIV Seropositive Male with Diffuse Large “B” Cell Lymphoma – A Rare Case Report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction with varied presentations. We report a rare case of DRESS syndrome with toxic epidermal necrolysis (TEN) overlap associated with non-Hodgkin lymphoma (NHL). A 52-year-old male with retroviral disease presented with fever and diffuse skin peeling with mucosal erosions. The patient was on antitubercular therapy (ATT) for 1 month for suspected tubercular cervical lymphadenitis. He had facial edema, extensive skin tenderness, and denudation with a positive Nikolsky’s sign, icterus, hepatosplenomegaly and multiple enlarged immobile nontender cervical, and axillary and inguinal lymph nodes. Investigations showed leukocytosis with hepatic and renal dysfunction. Skin histopathology was consistent with TEN. Based on Registry of Severe Cutaneous Adverse Reaction criteria, a diagnosis of ATT-induced DRESS with TEN overlap was made. Cervical lymph node biopsy and immunohistochemistry confirmed diffuse large B-cell NHL. ATT was withheld and the patient was treated with systemic steroids and assessed for initiation of chemotherapy. The profound immunological dysregulation in individuals with retroviral disease leads to varied clinical presentations, increasing the chances of diagnostic errors, and culminating in challenging scenarios. Therefore, seemingly innocuous symptoms and signs warrant thorough evaluation. Sound clinical acumen and prompt investigations for unusual causes such as malignancies can improve outcomes by aiding accurate diagnosis as well as avert untoward complications such as DRESS syndrome/TE.

Cytokine Release Syndrome (CRS) Is Not Required for CAR-T Cell Efficacy in Aggressive Large B-NHL

BACKGROUND Chimeric antigen receptor (CAR) T-cell therapy for treatment of aggressive large B-cell non-Hodgkin lymphoma (B-NHL) has changed management and outcomes for this disease. Treatment with CAR T-cells is accompanied by a unique set of adverse effects, including development of cytokine release syndrome (CRS). Though rates of CRS varied in trials, the development of severe (Grade 3 or 4) CRS was rare and similar incidences have been noted in real world studies. Here, we addressed whether the development of CRS is associated with outcomes in patients with aggressive large B-NHL undergoing treatment with CAR T cells. METHODS Patients aged ≥18 years with aggressive large B-NHL who underwent apheresis between May 2018 and January 2021 for commercial CAR T-cell therapy at eight academic US medical centers were identified from the Cell Therapy Consortium (CTC) registry. Providers could prescribe either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). CRS was graded using ASTCT consensus criteria. Tumor response 90 days after CAR T-cell infusion was assessed per Lugano criteria by the treating clinician. Persistent cytopenias were defined as ANC<1000 and/or Plt<50 and evaluated at the following intervals post infusion: day 30, 3 months, 6 months, 9 months, and one year. Cox regression analysis and the Kaplan Meier method were used for survival outcomes. Logistic regression analysis was used to assess association with tumor response and persistent cytopenias. RESULTS This study included 351 patients who underwent apheresis for commercial CAR T cell therapy for aggressive large B-NHL (Table 1A). Of these, 262 (74.4%) developed CRS while 90 (25.5%) did not. The median age at apheresis was 61 (range 18-88) among patients who developed CRS and 65 (range 37-85) among those who did not (p=0.005). Of the patients included, 202 (57.6%) received axi-cel and 149 (42.5%) received tisa-cel. With median follow up of 21.6 months, there were no differences in progression free survival (PFS) or overall survival (OS) between patients who developed CRS and those who did not. Median PFS in patients who did not develop CRS was 5.99 months compared to 5.89 months (p=0.99) in those who did. Median OS in patients who did not develop CRS was 26.6 months compared to 17.5 months in patients who did (p=0.16). Exploratory analysis showed that CRS grade did not influence PFS or OS (Figure 1). Results of the multivariate analysis are summarized in Table 1. The development of CRS did not have a significant impact on PFS or OS. A peak ferritin level of greater than 5000 within 28-days following CAR T-cell infusion was associated with worse PFS (HR 2.61; CI: 1.71-3.98, p<0.001) and OS (HR 2.38; CI: 1.50-3.76, p<0.001). LDH greater than the upper limit of normal was associated with worse progression-free (HR 2.11; CI: 1.49-2.98, p<0.001) and OS (HR 2.34; CI: 1.55-3.53, p<0.001). The administration of steroids for treatment of CAR T-cell associated toxicities had no significant impact on PFS or OS. Presence of bulky disease (≥10 cm) had no impact on PFS but was associated with worse OS (HR 1.81; CI: 1.29-2.75, p=0.005). Receipt of bridging therapy was associated with worse PFS (HR 1.58; CI: 1.11-2.24, p=0.011), though not OS. At 30 days post-infusion, there was no difference in ORR (66% vs 52%, p=0.081) or CR rate (39% vs 27%, p=0.155) between patients who developed CRS and those who did not. The occurrence of CRS within 28 days of treatment was significantly associated with cytopenias at day 30 (p=0.001), but not at any other time point. Amongst patients with Grade ≥3, 63% had cytopenias at day 30, compared to 47% among patients who did not have CRS (p=0.142). Grade ≥3 CRS was not significantly associated with cytopenias beyond day 30. CONCLUSION Survival outcomes were similar in patients with aggressive large B-NHL treated with CAR T-cell therapy who did or did not develop CRS. Furthermore, the occurrence of CRS had no impact on ORRs or CR rates. Having CRS was associated with cytopenias at day 30 post infusion, though not at subsequent time points. These findings lend further support to the finding that development of CRS does not impact efficacy of CAR T-cell therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictors and Outcomes of Immune Effector Cell Associated Neurotoxicity Syndrome in Patients Receiving Chimeric Antigen Receptor T-Cell Therapy for Aggressive B-Cell Non-Hodgkin Lymphoma

BACKGROUND Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for aggressive large B-cell non-Hodgkin lymphoma (B-NHL). Immune effector cell-associated neurotoxicity syndrome (ICANS) is recognized as an adverse event of special interest associated with CAR T-cell therapy. However, determinants of ICANS presentation and outcome remain poorly understood. In this multicenter retrospective study, we aimed to determine risk factors for ICANS and clinical outcomes in patients who develop ICANS. METHODS Patients aged ≥18 years with aggressive large B-NHL who underwent apheresis from May 2018 to January 2021 for commercial CAR T-cell therapy at eight academic US medical centers were identified from the Cell Therapy Consortium (CTC) registry. All centers were approved to administer axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) per provider discretion. ICANS and CRS were graded using ASTCT criteria and classified as severe if grade 3-5. Cox regression analysis and the Kaplan Meier method were used for survival outcomes. Laboratory values collected at lymphodepletion were used for the previously reported Endothelial Activation and Stress Index (EASIX) and modified EASIX (m-EASIX) score. Log transformation was applied to reduce skew. Predictors of severe ICANS were identified using logistic regression analysis. Best subset selection and receiver operating characteristic (ROC) analyses were applied to determine optimal predictors. RESULTS Baseline characteristics are summarized in Table 1. A total of 352 patients received axi-cel (n=203) and tisa-cel (n=149) with a median follow-up of 21.6 months. A total of 125 (35.5%) developed ICANS while 227 (69.8%) did not. Of those with ICANS, severe ICANS occurred in 75 (60%) and mild ICANS occurred in 50 (40%). The median age at apheresis was similar at 64 (range 22-89) compared to 62 (range 18-86) among patients with and without ICANS. The majority of patients who developed ICANS (87.2%) received axi-cel. CRS was more common in those with ICANS (94.4% vs. 63.3%). IPI grade 3 or higher was more common in patients who developed ICANS (59.9% vs. 47%). There were similar numbers of patients with bulky, primary refractory, and active CNS disease among patients with and without ICANS. Most patients with ICANS (82%) received steroids compared to those without ICANS (9.4%). Results of cox regression analyses are summarized in Table 2. The development of ICANS did not significantly impact PFS or OS nor did steroid administration. Exploratory analysis showed that severity of ICANS did not influence PFS or OS. Bulky disease (≥10 cm), LDH greater than the upper limit of normal, and peak ferritin greater than 5000 in the first 28-days post-infusion were associated with worse OS. There was a significant interaction term between ICANS and product for OS. We conducted an exploratory analysis stratified by product which showed that the development of ICANS with tisa-cel was associated with inferior OS (HR 3.65, CI: 1.35-9.91, p=0.011) but no difference in PFS. The development of ICANS with axi-cel had no impact on OS or PFS. Risk factors for ICANS evaluated as continuous variables at lymphodepletion included included ferritin (p=0.021), LDH (p=0.004), CRP (p<0.001), EASIX (p=0.004), and m-EASIX (p<0.001). Thrombocytopenia, neutropenia, and creatinine were not associated with severe ICANS. Best subset selection showed that higher CRP was the best model to predict severe ICANS. ROC comparison analysis showed no difference between CRP (AUC 0.64), EASIX (0.64), and m-EASIX (0.66). Post infusion, CRS (OR 2.27, CI: 1.46-3.08, p<0.001) and earlier onset of CRS (OR 0.83, CI: 0.71-0.94, p=0.005) were predictive of severe ICANS while time to steroid administration was not. CONCLUSION In this retrospective analysis, we showed that outcomes were similar in patients with aggressive large B-NHL treated with CAR T-cell therapy who did or did not develop ICANS regardless of severity. In stratified analysis, ICANS was associated with inferior OS in those who received tisa-cel but was limited by small sample size. Pre lymphodepletion CRP alone had the highest discriminatory ability to predict severe ICANS. After infusion, developing CRS and earlier onset of CRS were predictive of ICANS. Future studies should identify novel predictive scores for ICANS which may lead to strategies to prevent neurologic toxicity after CAR T-cell therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

LOCALIZED LARGE ENDOBRONCHIAL NON-HODGKIN LYMPHOMA PRESENTING WITH FEVER, DYSPNEA, AND HEMOPTYSIS

LOCALIZED LARGE ENDOBRONCHIAL NON-HODGKIN LYMPHOMA PRESENTING WITH FEVER, DYSPNEA, AND HEMOPTYSIS

Comparative clinical and economic assessment of polatuzumab vedotin therapy in combination with bendamustine and rituximab for adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma

Aim. To evaluate the pharmacoeconomic feasibility of using polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma.Materials and methods. Study design - retrospective analysis of literature data. Pharmacoeconomic research methods - clinical and economic analysis (incremental cost-effectiveness analysis, case-based approach) using sensitivity assessment. The sources of the drug efficacy data were publications on conducted clinical trials; on the drugs cost -the State register of maximum selling prices, data from the manufacturer's company.Results. Polatuzumab vedotin is the unique drug from the class of monoclonal antibody-antimitotic agent conjugates registered in Russia for the treatment of adult transplantation-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma. for this reason a case-based approach was applied as part of the cost-effectiveness analysis. As a result of clinical and economic analysis, it was found that the cost of progression free life-year added when using polatuzumab vedotin in combination with bendamustine and rituximab in patients with relapsed/refractory diffuse large b-cell lymphoma by 50.7 %, or by 11.4 million rubles, lower than the cost of progression free life-year added when using brentuximab vedotin in patients with relapsed/refractory Hodgkin's lymphoma. The sensitivity assessment showed the stability of the obtained results to changes in the input parameters of treatment cost and efficacy in a wide range of values.Conclusion. Use of polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult transplantation-ineligible patients with diffuse large B-cell non-Hodgkin's lymphoma is pharmacoeconomically justified and appropriate.

Molecular Profiling of Large B-Cell Lymphomas

Background: Large B-cell non-Hodgkin's lymphoma (NHL) comprises of a heterogeneous group of lymphomas with a high-grade morphology and aggressive nature. The diagnosis has gradually evolved from morphological characterization to classification of this group based on ancillary techniques such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular studies. Diffuse large B-cell lymphomas (DLBCL), not otherwise specified (NOS) is the most common B-cell NHL reported and a new diagnostic entity termed high-grade B-cell lymphoma harboring an MYC rearrangement with a BCL2 and/or BCL6 have been introduced by the WHO in 2017. MYC and BCL2/BCL6 proteins expression on IHC due to mutations leading to nuclear factor kappa B pathway activation is considered as double-expressor lymphoma (DEL). Materials and Methods: Sixty-two patients diagnosed with DLBCL, NOS on histopathology were subjected to IHC markers such as (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT, and Myc) and classified into activated B-cell and germinal center B-cell based on Hans' Algorithm. The samples were consequently subjected to tissue FISH for the detection of MYC, BCL2, and BCL6 gene translocations and classified as double-hit lymphoma (DHL)/triple-hit lymphoma (THL). The FISH results were subsequently compared for IHC expression of c-myc, Bcl2, and Bcl6. The staging, international prognostic index (IPI) scoring and lactate dehydrogenase levels were compared with progression-free survival (PFS) of 15 months among DHL/THL and DEL/TEL. Results: The median age of presentation among DLBCL-NOS patients is 58 years, while males (66.7%) were affected more commonly than females (33.3%). The majority of the patients presented with nodal involvement (71%) while extranodal involvement was seen in 29% cases. Hans' algorithm showed a significant P value with the IHC expression of BCL2, BCL6 and C-MYC. IHC and FISH correlation for BCL2 and BCL6 showed 100% sensitivity and 100% negative predictive value. IHC and FISH for c-MYC showed concordant results with a significant P &lt; 0.03. The clinicopathological results of S/D/THL showed association with higher stage disease, higher IPI scoring, and high Ki-67 index with inferior PFS. Conclusions: IHC MYC is a sensitive screening modality for MYC translocation and can be used for the identification of rearrangement in lower socioeconomic areas. Based on clinicopathological studies, all patients with DLBCL must undergo MYC FISH testing as these patients behave as high-grade lymphomas. Hence, a new entity DLBCL with MYC rearrangement without BCL-2/6 rearrangements maybe considered as a novel entity and to be studied in future cohorts.

Primary diffuse large b-cell lymphoma presenting as a chest wall mass: A case report

Chest wall lymphoma is a rare entity and often confused with the more common sarcoma. We report a case of diffuse large B-cell non-Hodgkin lymphoma patient presented with a sole chest wall mass. Chest computed tomography revealed an abnormal mass with well-defined borders below the pectoralis major muscle with contrast enhancement. The excisional biopsy revealed diffuse large B-cell non-Hodgkin lymphoma, confirmed by immunohistochemistry. The patient was then treated with six cycles of R-CHOP and achieved complete response. She is currently free from malignancy for 12 months after treatment. This paper illustrates the rarity of this entity, the need for distinguishing it from sarcoma, and briefly reviews its current management.

Functional activity of peripheral blood mononuclear cells in patients with non-Hodgkin's lymphomas receiving treatment after COVID-19 disease.

e19564 Background: Patients with non-Hodgkin's lymphomas (NHL) develop abnormalities in the structural and functional organization of the immune system leading to immune deficiency. Chemotherapy (CT) in patients after SARS-CoV infection is associated with a more severe disease course affecting the treatment results. The cytokine-producing activity (CPA) of blood cells is poorly studied, while it determines the effectiveness of antitumor and anti-infective functions of the immune system. The purpose of this study was to evaluate CPA of peripheral blood mononuclear cells in patients receiving treatment for NHL after COVID-19. Methods: The study included 8 patients with large B-cell NHL with PCR-confirmed COVID-19 infection in past medical history. All patients received from 3 to 4 chemotherapy cycles. K2EDTA blood samples obtained before and after 3-4 CT cycles were divided into 2 parts after dilution with a sterile nutrient medium solution: part 1, to assess spontaneous CPA; part 2, with addition of a sterile mitogen (phytohemagglutinin 4 μg, concanavalin A 4 μg, and lipopolysaccharide 2 μg) to assess stimulated CPA. The samples were incubated for 24 hours at 370C, and the levels of IL-1β, IL-6, IL-8, IL-10, IL-18, IL-4, IL-2, TNF- α, INF-ɣ, INF-α were determined in the obtained plasma. The stimulation coefficient (SC) was calculated as the ratio of stimulated CPA to spontaneous CPA. Results: 3-4 CT cycles in patients after COVID-19 was accompanied by an elevation of spontaneous CPA of the blood cells IL-6, INF-ɣ, TNF-α, IL-8, compared to the initial levels, by 678%, 127%, 64% and 57%, respectively. The ability of cells to spontaneous production of IL-10 and INF-α decreased by 30% and 100%. The mitogen-induced CPA of mononuclear cells in relation to IL-10, IL-6, IL-2, IL-1β and INF-α increased by 300%, 130%, 92%, 52% and 52%, respectively. Stimulated CPA in relation to INF-ɣ decreased by 21% compared to initial levels. As a result of the revealed CPA changes, SC in NHL patients after COVID-19 receiving CT increased, compared to the initial levels, by 465%, 92% and 48% respectively for IL-10, IL-2, IL-1β, as well as the appearing ability to INF-α production. SC for IL-6, INF-ɣ, TNF-α, and IL-8 decreased by 70%, 66%, 33% and 27% respectively. Conclusions: Certain features of spontaneous and mitogen-activated CPA of blood mononuclear cells were revealed in NHL patients after COVID-19, indicating a change in the functional activity of immune cells which could affect the development of the disease and the effectiveness of the therapy. The data obtained require additional studies and can be used to assess the condition of patients, as well as to predict the therapy efficacy.

Primary Extra Nodal Diffuse Large B-Cell Lymphoma of the Maxillary Sinus with Symptoms of Acute Pulpitis

Diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) is a subtype of large B-cell non-Hodgkin lymphoma with various clinical and pathological manifestations. DLBCL-NOS which primarily arises from maxillary sinus is rare and hard to diagnose due to unique anatomy. Here, we present a case of DLBCL-NOS that developed in the left maxillary sinus of a 72-year-old male, who presented with severe toothache that resembled acute pulpitis. The lesion was diagnosed and treated based on radiographs, histological, immunohistological examinations, and PET-CT analysis. Despite its rare incidence, DLBCL-NOS should still be included in differential diagnoses to rule out malignancy in cases of endodontic disease.

Magnetic resonance imaging apparent diffusion coefficient in lymphomas and its dependence on a number of technical and clinical factors

The purpose of this study was to determine the value of apparent diffusion coefficient (ADC) in various morphological variants of lymphomas, to study dependence of ADC on the anatomical location of lesions and technical scanning parameters to establish the usefulness in differentiating normal and involved lymph nodes (LN).Whole body MRI with diffusion-weighted imaging (DWI) was performed in 209 patients with lymphoma before treatment. A target LN was selected and ADC determined in each patient.The ADC value does not depend on the use of the parallel imaging technique (p= 0.56), higher when using built-in compared to superficial coil (p&lt; 0.0001), higher when using respiratory triggering than free breathing (p&lt; 0.02). The highest ADC values (х10-3mm2/s) were obtained in the involved LN of the lung hilar (1.429 ± 0.396) and mediastinum (1.338 ± 0.313), lower values (p&lt; 0.01) - in the LN of the abdomen (1.011 ± 0.298), axillary (0.840 ± 0.196), neck (0.834 ± 0.259), inguinal (0.753 ± 0.128) and iliac (0.738 ± 0.129). Depending on the morphological variant of lymphoma, the highest ADC value was obtained in Hodgkin lymphoma - 1.168 ± 0.372 (p&lt; 0.0002). ADC in diffuse large B-cell non-Hodgkin lymphoma was 0.951 ± 0.320, indolent non-Hodgkin lymphomas - 0.756 ± 0.246, mantle zone non-Hodgkin lymphoma - 0.759 ± 0.211.In conclusion, DWI in lymphoma should be performed using surface coil, parallel imaging, and free breathing. Statistically significant differences in ADC were found depending on the anatomical location of the lesions and the morphological variant of lymphoma. Given the dependence of ADC on various technical and clinical factors, it is not possible to establish a single threshold value for differentiating involved and normal LN. The use of the LN size criterion for this purpose is the most optimal in lymphoma.

Diffuse Large B-Cell Non-Hodgkin Lymphoma Involving Multiple Different Organs in a Young Adult with &lt;sup&gt;18&lt;/sup&gt;F-FDG PET/CT

Extranodal-multiorgan involvement is rarely presented in diffuse large B-cell non-Hodgkin lymphoma. 18Fluorine-fluorodeoxyglucose positron emission tomography/computed tomography findings of a 22-year-old female patient with supra/infra-diaphragmatic nodal and skeletal involvements and thyroid, pancreas, right breast, bilateral renal, and ovarian involvements were presented.

Patient Reported Outcomes in Metastatic Spine Disease: Concurrent Validity of PROMIS with the Spine Oncology Study Group Outcome Questionnaire.

Cross-sectional prospective study. To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression domains in comparison to the Spine Oncology Study Group-Outcomes Questionnaire (SOSG-OQ) in patients with metastatic spine disease. While there remains a significant movement toward incorporating patient-reported outcome measures (PROMs) into clinical care, there are few validated PROMs for patients with metastatic spine disease. The SOSG-OQ was designed and validated for metastatic spine tumor patients. However, the use of general symptom-based PROMs, such as PROMIS domains, may reduce both patient and physician burden and improve interdisciplinary care if shown to be concurrently valid. Metastatic spine tumor patients from January 2017 to July 2021 at a single academic medical center were asked to complete PROMIS PF, PI, and Depression domains and the SOSG-OQ. Spearman correlation (p) coefficients were calculated. A total of 103 unique visits, representing 79 patients met our inclusion criteria. A majority were men (59; 57%) and Caucasian (93; 90%), and the average age was 64-years-old (range: 34-87). There were 13 different types of histologies reported, with multiple myeloma, breast cancer, and prostate cancer representing 28 (27%), 26 (25%), and 13 (13%), respectively. Additional cancers included renal cell carcinoma, lung cancer, colon cancer, thyroid cancer, large B-cell lymphoma, nonHodgkin lymphoma, esophageal cancer, plasmacytoma, metastatic paraganglioma, and metastatic spindle cell sarcoma. SOSG-OQ was strongly correlated with PROMIS PI (ρ = 0.78) and PROMIS PF (ρ = 0.71), and moderately correlated with PROMIS Depression (ρ = 0.58). PROMIS PF, PI, and Depression appear to capture similar clinical insight as the SOSG-OQ. Spine surgeons can consider using these PROMIS domains in lieu of the SOSG-OQ in metastatic spine tumor patients.

Prognostic values of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) expression in tissues of diffuse large B-cell non-Hodgkin lymphoma patients - an immunohistochemical study.

IntroductionDiffuse large B-cell non- Hodgkin lymphoma (DLBCL) is the largest common category of adult lymphoma. Recurrence and treatment resistance occurs in one-third of cases, triggering them to the progressive stage of DLBCL after treatment. Detection of novel predictive and prognostic biomarkers leads to improvement of its treatment and prognosis.Aim of the studyTo assess the prognostic roles of protein expression of myeloid differentiation factor 88 (MYD88) and transducin (β)-like receptor 1 (TBLR1) in tissues of DLBCL patients.Material and methodsIn the current study we included tissues from 100 cases of DLBCL. For immunohistochemistry, tissues were stained with MYD88 and TBLR1. We followed patients for about 3 years, and then we correlated their expression with clinicopathological and prognostic parameters.ResultsHigher MYD88 and TBLR1 expressions were associated with presence of B symptoms, fever, night sweat, advanced stage, bone marrow involvement and bulky nodal size, presence of extra-nodal extension, unfavourable relapse-free survival, and unfavourable overall survival rates (p < 0.001).Conclusionsoverexpression of MYD88 and TBLR1 expression was present in DLBCL patients and was associated with unfavourable clinicopathological and prognostic parameters.

Safety and Efficacy of Vibostolimab and Pembrolizumab in Patients with Relapsed or Refractory Hematologic Malignancies: A Multicohort, Open-Label, Phase 2 Study

Background: The T-cell immunoglobulin and ITIM domain (TIGIT) is highly coexpressed with programmed cell death 1 (PD-1) on both CD4 and CD8 T cells in cancers. Blockade of TIGIT with vibostolimab (MK-7684) has demonstrated antitumor activity in multiple preclinical tumor models. Inhibition of the PD-1 pathway with pembrolizumab has demonstrated efficacy and safety in several hematologic malignancies. Enhanced antitumor activity with anti-TIGIT and anti-PD-L1 combination therapy has been seen in a preclinical model. A multicohort, open-label, phase 2 study will evaluate the safety and efficacy of MK-7684A, a coformulation of vibostolimab and pembrolizumab, in patients with relapsed or refractory (r/r) hematologic malignancies.Study Design and Methods: This two-part phase 2 study includes a signal-finding phase (part 1) with the option for a dose-expansion phase (part 2), depending on the observed risk-benefit profile from part 1. Patients must have confirmed diagnosis of r/r disease, including classical Hodgkin lymphoma (cHL; cohort A or B), primary mediastinal B-cell lymphoma (PMBCL; cohort A or B), follicular lymphoma (FL; cohort C), diffuse large B-cell lymphoma (DLBCL; cohort D), multiple myeloma (MM; cohort E), or non-Hodgkin lymphoma (NHL; cohort F) (Table 1). Three hundred thirty participants are expected to enroll in part 1 (signal finding) and part 2 (cohort expansion). In part 1, patients in cohorts A-F will receive MK-7684A (vibostolimab 200 mg + pembrolizumab 200 mg) by IV infusion every 3 weeks (Q3W) for up to 35 cycles. Patients will continue treatment until investigator-determined PD, start of new anticancer treatment, documented complete response, or completion of maximum 35 cycles of treatment. Safety data from the first 12 treated patients from any cohort will be collected. Dose-limiting toxicities (DLTs) will be monitored for the first 6 weeks of continuous treatment. If ≥5 of the 12 patients experience DLTs during this period, enrollment may be discontinued. After the DLT review period, safety data will be collected every 6 months for all enrolled patients. Efficacy assessments will be performed Q3W, with the initial tumor imaging performed ≤28 days after enrollment and repeated at 12 weeks (cohorts A-D, F) or 4 weeks (cohort E) after enrollment. Adverse events (AEs) will be monitored throughout the study, and severity will be graded according to the guidelines outlined in NCI CTCAE version 5.0. Each patient will be monitored for AEs and serious AEs for 30 day and 90 days, respectively, after discontinuation of study intervention. The primary end point for part 1 is the number and proportion of patients with DLTs, AEs, and discontinuations from study treatment due to AEs. Safety and tolerability will be assessed by clinical review. Secondary end points include investigator-assessed objective response rate, investigator-assessed duration of response, disease control rate, and pharmacokinetic end points. Overall survival, progress-free survival, health-related quality of life assessments, and molecular assessments will be exploratory. In the part 2 dose-expansion phase, the plan is to enroll approximately 120 patients from cohorts B-E to receive up to 35 cycles of MK-7684A Q3W; 30 additional patients may be enrolled in a cohort expansion (cohort G) to receive vibostolimab monotherapy Q3W for up to 35 cycles. Cohort G will include patients with cHL or PMBCL with PD after ≥2 or ≥3 prior therapies, FL after ≥2 prior therapies, DLBCL after ≥2 prior therapies, and/or MM after ≥3 prior therapies. [Display omitted] DisclosuresYusuf: Merck & Co., Inc.: Current Employment. Jemielita: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Marinello: Merck & Co., Inc.: Current Employment, Other: Current Stockholder.

Single institution retrospective review of CD34+ apheresis collection based on mobilization regimen and primary diagnosis

Abstract Introduction/Objective Plerixafor has been increasingly used in conjunction with G-CSF to increase mobilization of CD34+ stem cells in patients undergoing leukapheresis collection for autologous stem cell transplantation. While G- CSF and plerixafor have been shown to increase CD34+ counts, studies examining patients’ ability to meet collection goals for patients with multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) have not been well documented. Methods/Case Report All autologous stem cell collection patients between 2017-2021 were retrospectively reviewed and categorized by primary diagnosis. Patients received a mobilization regimen of G-CSF alone, G-CSF and plerixafor, G-CSF and chemotherapy, or G-CSF, plerixafor, and chemotherapy. CD34+ stem cell collection results were recorded. All units of CD34+ stem cells were processed according to protocol and viability was assessed by Trypan blue method on a thawed aliquot 2 weeks after processing. Results (if a Case Study enter NA) 385 patients (271 MM, 41 DLBCL, 30 HL, and 43 NHL patients; male: 242; female: 143; age range: 16-78) were identified. Binomial logistic regression demonstrated that use of plerixafor with G- CSF was negatively associated with meeting CD34+ goal collection (OR= -1.57, p= 0.003) compared to G-CSF alone. This result was particularly true for MM patients (OR= -1.62, p= 0.014). A pairwise t-test indicated that patients receiving G-CSF and plerixafor had lower CD34+ cell viabilities (t= 2.21, p = 0.028); after Bonferroni correction for multiple comparisons, MM samples also had significantly lower percentage viability than DLBCL (p= 0.003) or HL (p= 0.022) samples. Conclusion A higher percentage of patients mobilized on G-CSF alone were able to meet collection goal versus patients who were mobilized on G-CSF and plerixafor. Patients who received G-CSF and plerixafor had significantly lower viability than those who received G-CSF alone. We hypothesize these findings to be due to lower baseline mobilization for patients on G-CSF and plerixafor.

Assessment of Neutrophil/Lymphocyte Ratio in Relation to Presentation and Prognosis of Diffuse Large B-Cell Nonhodgkin Lymphoma

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is representing 30%–40% of all lymphomas. It is an aggressive lymphoma with heterogeneous clinicopathological features. Inflammatory processes have been identified to play an important role in the pathogenesis of lymphoma including the neutrophil-lymphocyte ratio (NL ratio) was associated with a poor prognosis. AIM OF STUDY: The aim of this study is to assess neutrophil/lymphocyte (N/L) ratio in relation to clinical presentation, and other prognosticators in DLBCL, and to study the effect of these markers with response rate and early outcome. PATIENTS AND METHODS: This is a cohort prospective study with data obtained from May 2018 to November 2019. Data collected from multiple hematological centers in Baghdad, Iraq. A total of 58 adult patients who are newly diagnosed with DLBCL were enrolled. In addition to demographic features, international prognostic index (IPI) score, complete blood parameters (white blood cell count, N/L ratio, had assessed. RESULTS: The mean age was 53.54 ± 14.95 years. Twenty-two (45.83%) had extranodal involvement at the presentation. Advanced stage was reported in 34 (70.83%). Median N/L ratio was 3.39 with cut-off values 4.41. There was no significant association with the N/L ratio neither with progression-free survival (PFS) nor with the advanced stage presentation (P = 0.238, 0.343, respectively). It is found also that higher median N/L ratio was significantly associated with high and high-intermediate IPI score (P = 0.03). CONCLUSION: The NL ratio has a significant association with the IPI score, but not with the disease PFS.

Can the Autologous Transplant of Hematopoyetic Progenitors be Considered an Effective Alternative to Increase Global Survival in High-Grade Non-Hodgkin Lymphomas?

BACKGROUNDDiffuse large B-cell non-Hodgkin's lymphoma (NHL) is the most common High Grade Lymphoma obtaining complete responses up to 70% with chemotherapy (R-CHOP) 1. Transplantation has been implemented as an alternative, however in this lymphoma There have been few benefits compared to other treatments.2Transplantation of hematopoietic progenitors is a complex and costly process requiring infrastructure, specialized personnel as well as specialized laboratory medication and support8. However, in our country, both the infrastructure and the economic resources of the health services are limited, so that the management and selection strategies of patients eligible for transplantation should be more rigorous. At present, we do not have a study in our country that exemplifies what studies such as the PARMA and CORAL have shown, in which the lack of effectiveness of this transplant in the LDCBG has been shown 3,4. OBJETIVETo evaluate the overall survival of patients with high-grade NHL in treatment with R-CHOP with and without autologous transplantation of hematopoietic progenitors. MATERIAL AND METHODSRetrospective, longitudinal, observational study of patients with high-grade lymphoma who received AHPC against those who did not receive it, previously all received R-CHOP treatment. Data obtained through a transplant census of Specialties Medical Unit No. 25, Monterrey, Nuevo León Mexico, we used central tendency and dispersion tests as well as Kaplan Meier curves, considering a significant p ≤ 0.05. SPSS software13.0Determining the survival time of each group, comparing both means and proportions and the time before relapse. Follow-up within a time period of 1 to 9 years. RESULTS65 patients with diffuse large B-cell NHL were collected in the 2003-2015 period. We evaluated the effect of autologous transplantation vs transplant recipients; mean age 49.9 ± 13.9 years with highest proportion of men versus women 52.31% vs 47.69%. Comparing SLE and SG, OR for gender variable and Cox regression for more relevant variables. CONCLUSIONWhen comparing the SLE and SG curves between the group that was transplant and the one that did not receive it, we did not find a statistically significant difference. It is not possible to state that autologous transplantation substantially modifies the prognosis of patients with diffuse large B-cell NHL. The results are consistent with those previously reported in other studies5,6,13-15 . New prospective, multicenter, and larger sample size studies are planned to more accurately determine the efficacy and safety of AHPC as part of treatment Large B-cell NHL. DisclosuresNo relevant conflicts of interest to declare.

A Phase I Study of the Anti-CD79b THIOMABTM-Drug Conjugate DCDS0780A in Patients (pts) with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL)

A Phase I Study of the Anti-CD79b THIOMABTM-Drug Conjugate DCDS0780A in Patients (pts) with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL)

Ovarian dlbcl presenting as a very large ovarian mass in a young woman – a case report (and potential frozen section pitfall)

While ovarian involvement as a late manifestation of disseminated non-Hodgkin lymphoma (NHL) is not uncommon, primary ovarian NHL, or NHL presenting for the first time as an ovarian mass, is rare, having a reported incidence of around 0.5% of all untreated NHL and 1.5% of untreated ovarian neoplasms. This case study reports a 27-year-old woman who underwent a unilateral salpingo-ophorectomy and staging for a very large, rapidly enlarging, right ovarian mass, suspected clinically of being a dysgerminoma. On frozen section, the tumour was favoured to be a germ cell tumour, with juvenile granulosa cell tumour also not excluded. On permanent section, however, the tumour more clearly demonstrated morphological features and immunological features in keeping with a large B-cell non-Hodgkin lymphoma. Coupled with FISH analysis showing no evidence of a MYC gene rearrangement, a diagnosis of DLBCL, NOS, double expressor phenotype, was ultimately made. This case serves as a reminder that, although rare as an initial presentation in the ovary, lymphoma should be considered by pathologists in the differential diagnosis of ovarian tumours, including at frozen section, where consideration should also be given to obtaining fresh tissue for flow cytometry. 1.Dimopoulos MA, Daliani D, Pugh W, et al. Primary ovarian non-Hodgkin's lymphoma: outcome after treatment with combination chemotherapy. Gynecol Oncol 1997; 64: 446–50.

213 - Impact of Pre-Treatment Whole-Body Metabolic Tumor Volume on Toxicities and Outcomes in Patients Treated with Anti-CD19 CAR T-Cell Therapy for Aggressive Large B-Cell NHL

213 - Impact of Pre-Treatment Whole-Body Metabolic Tumor Volume on Toxicities and Outcomes in Patients Treated with Anti-CD19 CAR T-Cell Therapy for Aggressive Large B-Cell NHL