Large B-cell non-Hodgkin Lymphoma Research Articles

Intraocular manifestation of a diffuse large B-cell non-Hodgkin lymphoma of the pancreas.

Intraocular manifestation of a diffuse large B-cell non-Hodgkin lymphoma of the pancreas.

Molecular Disease Monitoring in Patients With Relapsed/refractory B-Cell Lymphoma Receiving Anti-CD19 CAR T-Cell Therapy

BackgroundChimeric antigen receptor (CAR) T-cell therapy has improved the historically poor outcomes for relapsed and refractory (R/R) large B-cell non-Hodgkin's lymphoma (LBCL). However, nearly 60% of patients will either fail to respond or relapse after CAR T-cell therapy. Currently, PET/CT scans are used to assess response. Cell-free circulating tumor DNA (ctDNA) is released by tumor cells into the peripheral blood and can be measured for minimal residual disease (MRD) assessment. MethodsIn this retrospective, IRB approved pilot study, archived lymphoma tissues and ctDNA from peripheral blood samples on day 0, 14, 28, 56, 90, 180, and 365 after CAR T-cell infusion from 10 patients with R/R NHL were collected for next-generation sequencing (NGS) of clonal variable-diversity-joining (VDJ) rearrangements (Adaptive biotechnologies [Seattle, WA]). Response was assessed by PET/CT on days 90 and 365 and graded according to the Lugano 2014 criteria. The primary endpoint was to determine the feasibility of detecting ctDNA to monitor disease response after anti-CD19 CAR T-cell therapy. The secondary endpoint was to compare the sensitivity/specificity of MRD assessment from ctDNA to PET/CT imaging. ResultsNine out of 10 patients with a trackable sequence [median age 69 (range: 56-76); 55.6% male; median LDH 224], were included in this study. Each received tisagenlecleucel (tisa-cel) CAR T-cell therapy after median 2 prior treatments (range: 2-4). 7/9 patients had R/R diffuse large B-cell lymphoma (DLBCL), and 2/9 had transformed follicular lymphoma. At a median follow up of 12.7 months (range: 1.5-30 months), 4 patients were alive. By day 90, 3 patients (33.3%) achieved a radiographic complete response (CR) whilst 6 patients (66.6%) had progressive disease (PD). Detectable MRD on day 14 or day 28 had 83% sensitivity and 100% specificity for radiographic progression at any time before 1 year. For patients with PD, the median (interquartile range) MRD at day 0, 14, and 28 were 17.31 (1.01, 96.84), 9.12 (0.30, 18.8), and 23.77 (8.01, 137.53) copies per milliliter (mL), respectively. For patients with detectable MRD at day 28, mOS and mPFS were 6.7 and 1.3 months, respectively. ConclusionMonitoring MRD was a sensitive and specific method to detect poor response to tisa-cel. Additional studies evaluating MRD more frequently and with different products are warranted.

Rare Case of Primary Effusion Lymphoma mimicking Pulmonary Tuberculosis

Primary effusion lymphoma (PEL) is a rare large B-cell non-Hodgkin lymphoma (NHL) that usually occurs in immunosuppressed individuals in advanced stages of the disease, presenting as body cavity effusions without detectable tumor mass. We report a 61-years old man presented to the emergency room complaining of effort-related dyspnoea, low-grade fever, night sweats, and a dry cough for several days. He was then put on empirical anti-tubercular treatment (ATT) suspecting Pulmonary Tuberculosis. General examination revealed a decrease oxygen saturation, tachypnea, a bulging tenderness lymph node on the neck. Chest computerized tomography (CT) scan indicated pericardial and pleural effusion with mediastinal dilatation suspected thymoma or lymphoma. A Cardiocentesis needle aspiration was performed; however, the histological pattern was not specific. The patient underwent a surgical biopsy of a left supra-clavicular lymph node. A Classical Hodgkin lymphoma nodular sclerosis type was found in the histopathology examination. Immunohistochemistry detected the tumour cellular markers (i.e., CD30). Chemotherapy treatment for 6 cycles resulted an excellent outcome. In conclusion, radiologists play a vital role in the diagnosis of PEL, detecting effusions in body cavities and excluding the existence of solitary masses or pleural nodules or masses, ultimately narrowing down the differential diagnoses.

The impact of MYD88 and PIM1 in mature large B-cell non-Hodgkin lymphomas: Defining element of their evolution and prognosis.

Sequence studies of the entire exome and transcriptome of lymphoma tissues have identified MYD88 and PIM1 as involved in the development and oncogenic signaling. We aimed to determine the frequency of MYD88 and PIM1 mutations, as well as their expressions in conjunction with the clinicopathological parameters identified in mature large B-cell non-Hodgkin lymphomas. The ten-year retrospective study included 50 cases of mature large B-cell lymphoma, diagnosed at the Pathology Department of the Emergency County Hospital of Constanţa and Săcele County Hospital of Brasov. They were statistically analyzed by demographic, clinicopathological, and morphogenetic characteristics. We used a real-time polymerase chain reaction technique to identify PIM1 and MYD88 mutations as well as an immunohistochemical technique to evaluate the expressions of the 2 genes. Patients with lymphoma in the small bowel, spleen, brain, and testis had a low-performance status Eastern Cooperative Oncology Group (P = .001). The Eastern Cooperative Oncology Group performance status represented an independent risk factor predicting mortality (HR = 9.372, P < .001). An increased lactate dehydrogenase value was associated with a low survival (P = .002). The international prognostic index score represents a negative risk factor in terms of patient survival (HR = 4.654, P < .001). In cases of diffuse large B-cell lymphoma (DLBCL), immunopositivity of MYD88 is associated with non-germinal center B-cell origin (P < .001). The multivariate analysis observed the association between high lactate dehydrogenase value and the immunohistochemical expression of PIM1 or with the mutant status of the PIM1 gene representing negative prognostic factors (HR = 2.066, P = .042, respectively HR = 3.100, P = .004). In conclusion, our preliminary data suggest that the oncogenic mutations of PIM1 and MYD88 in our DLBCL cohort may improve the diagnosis and prognosis of DLBCL patients in an advanced stage.

Non-Hodgkin large B-cell lymphoma of the bile duct mimicking a Klatskin tumor: case report

The obstruction of the bile duct secondary to non-Hodgkin lymphoma is extremely rare. That's why we present the case of a 63-year-old female patient who sought medical attention due to jaundice, dark urine, acholia, and weakness. Laboratory results showed a cholestatic pattern, and an ultrasound revealed dilation of the intra and extrahepatic bile ducts, for which a cholangio resonance was ordered. It showed an expansive formation with ill-defined borders compromising the common hepatic duct associated with its stenosis. The initial suspicion was a Klatskin tumor, for which a biopsy was performed, which reported infiltration of a double expressor large B-cell lymphoma as a primary neoplasm of the bile duct. The patient underwent chemotherapy treatment with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and went into remission. Due to continuous episodes of cholangitis, a Roux-en-Y hepatic jejunal anastomosis with biliary tract reconstruction was performed. Currently, she remains in remission, seven years after the diagnosis. This case highlights the rarity of large B-cell non-Hodgkin lymphoma in the bile duct and emphasizes the importance of biopsy for effective treatment, combining chemotherapy for the underlying disease and surgery for obstructive complications.

Quantitative Ki-67 Proliferative Index Assessment of Human B-Cell Lymphomas By Flow Cytometry

Background: The Ki-67 proliferative index is used as a diagnostic and prognostic marker in the classification of B-cell non-Hodgkin lymphomas (NHL). Despite its semiquantitative nature, immunohistochemistry (IHC) evaluation of Ki-67 in histologic specimens is the gold standard. The aim of this study was to determine the correlation of quantitative Ki-67 expression by flow cytometry (FCM) with standard IHC in samples of B-cell NHL. Methods: We performed a retrospective observational study of bone marrow and tissue biopsies evaluated for routine lymphoma screening between January 2021 and December 2022. FCM analysis was performed according to Euroflow standard LST screening. Positive samples were further characterized, and Ki-67 expression was integrated using a PerCP-Cy5.5 fluorochrome-conjugated monoclonal antibody after cell fixation and permeabilization. The Ki-67 proliferative index was calculated as all positive events among the neoplastic population (%). Ki-67 proliferative index by flow cytometry was compared with Ki-67 proliferative index by IHC. Clinical data were retrieved from the electronic database. This study was approved by the institutional IRB and clinical ethics committee. Results: A total of 51 samples from 50 patients were evaluated: 4 bone marrow aspirates, 8 fine-needle aspirations (FNA) and 39 tissue biopsies. Median age at diagnosis was 67 years (interquartile range [IRQ], 60-79 years), and 45% were female. A low-grade lymphoma was diagnosed in 27 cases (52.9%; 20/27 follicular lymphoma), a high-grade lymphoma case in 23 cases (45.1%; 20/23 diffuse large B-cell lymphoma), and mantle cell lymphoma in 1 case. Median Ki-67 proliferative index by FCM was 41.4% (range, 1 - 100%) and 54.8% (range, 5 - 100%) by IHC. Overall, the Ki-67 proliferation index by FCM showed a significant correlation coefficient of 0.925 with IHC (95% IC 0.870 - 0.957, p &amp;lt; 0.0001). There was a negative constant bias of -13.35% (-46.87 to 20.16), which was greater in the range of 30-80% of Ki-67 expression by IHC. Indolent lymphomas displayed a lower proliferative index by FCM compared with IHC (5 vs 20%, p&amp;lt;0.001). No difference was seen among aggressive lymphomas. Fourteen cases had a difference in the proliferative index &amp;gt;20%, 10/14 were follicular lymphoma, 2/14 were indolent lymphoma transformations and 2 were large B-cell NHL. In all cases FCM displayed lower results compared with IHC. Conclusions: Our data suggest that the Ki-67 proliferative index can be accurately assessed by flow cytometry. A correlation bias seems clinically meaningful in intermediate values of Ki-67. The quantitative nature of FCM-based proliferative index may improve the prognostic potential of Ki-67, especially for indolent or borderline histologies. Further validation studies are warranted.

The significance of concurrent MYC and BCL2 expression in Egyptian patients with diffuse large B-cell NHL

This study aimed to investigate the frequency of MYC/BCL2 co-expression using immunohistochemistry (IHC) in Egyptian patients with diffuse large B-cell lymphoma (DLBCL) and its impact on treatment outcomes, overall survival (OS), and disease-free survival (DFS). A total of 100 adult patients with newly diagnosed DLBCL were included in the study and treated with the R-CHOP regimen. The cases were classified into germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB) subtypes based on IHC. Our results showed that a subset of the studied cases didn’t achieve complete remission (CR) after chemotherapy (22%). Co-expression of MYC and BCL2 was observed in 20% of the cases, with most of them belonging to the non-GCB subtype. The CR rate was significantly lower in the double-expressor (DE) group (45%), while no significant difference was observed in CR between the GCB and non-GCB cases. The DE group was associated with advanced stage, extra-nodal involvement, and high-risk R-International Prognostic Index (R-IPI). Both the non-DE and GCB groups demonstrated better DFS, while the non-DE group only showed better OS. Both non-DE status and GCB subtype were identified as independent factors affecting DFS. In conclusion, the concurrent expression of MYC and BCL2 in DLBCL indicates an inferior outcome and lower chemotherapy response. The current chemotherapeutic strategy has not effectively improved the outcomes of this aggressive lymphoma subtype. Therefore, the identification of these patients is crucial for selecting appropriate treatment options.

THU111 Diffuse Large B-Cell Lymphoma Pituitary Metastasis

Abstract Disclosure: M.S. Martinez Cruz: None. C.J. Haas: None. S.Z. Bhat: None. Background: The Hypothalamus-Pituitary axis (HPA) is a rare location for metastasis of non-Hodgkin’s lymphoma. Case description: A 57-year-old woman presented to the emergency department with a one day of acute, severe fatigue, nausea, and anorexia. She reported a history of stage IIIB diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) treated with R-CHOP three months prior, complicated by a recent recurrence in the lumbar spine requiring a short dexamethasone taper and radiation therapy two weeks prior to admission. On presentation, she remained hemodynamically stable with an otherwise unremarkable exam. Diagnostics revealed severe hypotonic hyponatremia suggestive of syndrome of inappropriate antidiuretic hormone (SIADH). CT scan of the head revealed thickening of the paramedian hypothalamic structures and the pituitary infundibulum. Subsequent pituitary MRI w/wo contrast demonstrated marked thickening and enhancement of the infundibulum with restricted diffusion, as well as T2/FLAIR hyperintensity and thickening in multiple hypothalamic areas concerning for HPA metastasis. Hormonal workup demonstrated panhypopituitarism for which she was started on hydrocortisone and levothyroxine. Lumbar puncture was performed with CSF flow cytometry revealing phenotypically abnormal monoclonal B-cells consistent with DLBCL leptomeningeal metastasis. Three days prior to induction chemotherapy, she developed massive polyuria, with a rapid increase in the serum sodium and markedly low urine-specific gravity consistent with acute diabetes insipidus (DI). Management included vasopressin, as needed, followed by standing doses of desmopressin. She was initiated on methotrexate and leucovorin chemotherapy. However, three week later, she developed acute onset diplopia, headache, nausea and vomiting, urinary and bowel incontinence, and fatigue. Follow-up pituitary MRI revealed progression of her known HPA metastatic disease, and she passed away one month later. Conclusion: This is an unprecedented case of metastatic DLBCL to the leptomeninges, hypothalamus, and pituitary infundibulum confirmed by CSF cytologic analysis that presented in the context of associated panhypopituitarism that manifested initially as SIADH followed by sudden DI. Abbreviations: R-CHOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone Presentation: Thursday, June 15, 2023

Optimization of Metabolic Tumor Volume as a Prognostic Marker in CAR T-Cell Therapy for Aggressive Large B-cell NHL

BackgroundCD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphomas (B-NHL) though the majority of recipients do not receive durable disease benefit, prompting the need to better define risk factors for relapse/progression. ObjectivesWe performed a single-center, retrospective analysis of patients treated with commercial CAR T-cell therapy to evaluate the impact of tumor burden, as measured by whole-body metabolic tumor volume (MTV) from 18F fluorodeoxyglucose PET imaging, on treatment outcomes. Study DesignSixty-one patients treated with CAR T-cell therapy for R/R B-NHL between May 2016 and November 2021 were included. ResultsUsing a receiver operating characteristic curve-based MTV optimization cutoff of 450 mL, 1-year progression-free survival (PFS) was 22% for high MTV versus 54% for low MTV (P < .01), and 1-year overall survival (OS) was 37% and 73%, respectively (P = .01). In a subset of 46 patients, residual MTV of less than 106 mL at the day 30 (D30) disease assessment was associated with significantly improved outcomes (1-year OS 85% vs. 13%, P < .01). Incorporation of pretreatment MTV to the International Prognostic Index (IPI) scoring system significantly distinguished 2-year PFS and OS outcomes by 3 risk groups. ConclusionsOur findings suggest that both pretreatment and D30 MTV are predictive of outcomes among R/R B-NHL patients treated with CAR T-cell therapy. These data indicate that efforts to reduce pretreatment tumor burden may improve longitudinal clinical outcomes. Furthermore, D30 postinfusion MTV quantification may aid clinicians in optimally identifying patients at high-risk for progression, and in whom closer disease monitoring should be considered. MTV also adds prognostic value to patients with high-risk IPI and holds promise for incorporation in novel risk scoring systems which can identify patients prior to CAR T-cell therapy at highest risk of adverse outcomes.

A case of primary multiple synchronous radiogenic cancer in clinical practice

There is an increase in the number of patients with secondary malignant neoplasms. In addition, in some subgroups after radical cancer treatment, the lifetime risk of developing secondary malignant neoplasms can be as high as 33 %. Secondary malignancies remain an important cause of death in patients who have received radical cancer treatment. The presented clinical case demonstrates the risk of developing primary multiple malignant neoplasms after radiation therapy and chemotherapy. A 39‑year-old patient with diffuse large B-cell non-Hodgkin lymphoma underwent definitive treatment including chemo-and radiotherapy. Ten years later, the patient developed the induced multiple malignant tumors: a malignant neoplasm of the heart — myofibrosarcoma of the right ventricle with invasion of the anterior wall of the right ventricle Stage IIIB G2T3N0M0, left breast cancer Stage IIIA T3N2M0. The choice of treatment tactics for this category of patients remains particularly difficult.

Laryngeal Anaplastic Lymphoma Kinase-Positive B-cell Lymphoma: Case Report and Review.

Larynx is an uncommon extranodal site for non-Hodgkin lymphoma (NHL). Anaplastic lymphoma kinase (ALK)-positive B-cell lymphoma is a rare and aggressive form of NHL. A 19-year-old male presented to the ENT department with globus sensation, hoarseness, cervical lymphadenopathy and weight loss. A 70-degree rigid endoscopic examination of the larynx showed a vascular, irregular, submucosal mass arising from the right aryepiglottic fold causing near complete obstruction of the laryngeal airway. PET-CT showed hypermetabolic lesions in the supraglottis, cervical lymph nodes, cervical spine, ribs and abdominal lymph nodes. Biopsy was taken from the supraglottic mass as well as the enlarged cervical lymph nodes, which revealed ALK-positive large B-cell NHL. In this report, we present a rare case of ALK-positive large B-cell NHL of the larynx, discussing its clinical, radiological and pathological features. A limited review of literature is also presented. There is a need to develop a database for the description of lymphomas affecting the larynx and this case report adds to the existing knowledge of this rare entity.

Case Report on Diffuse Large B-Cell Non-Hodgkin Lymphoma with a Spontaneous Bowel Perforation

Background: Intestinal Non-Hodgkin lymphoma is an uncommon cause of acute abdominal pain. The main objective of the present case report is to share our experience with Diffuse Large B Cell Non-Hodgkin Lymphoma with spontaneous bowel perforation in a setting of HIV. Method: Description of a Case Report Diffuse Large B-Cell Non-Hodgkin Lymphoma with a spontaneous bowel perforation: A 39-year-old female patient presented with a one-day history of acute abdomen. She is known retroviral disease reactive with CD4 count 534, Viral Load 131 on Antiretroviral Treatment-Fixed Dose Regimen duration of more than 5 years and was being treated for Peptic Ulcer Disease. Chest X-ray: showed pneumoperitoneum consistent with a perforation. A Laparotomy was performed and found a perforated Jejunum leaking small bowel contents. Resection and primary anastomosis were performed, and washout was done. Post-Operative condition was uneventful, and she was discharged four days after the operation. The resected portion was sent for histology, which showed perforation of the Jejunum secondary to a Diffuse Large B Cell Non-Hodgkin Lymphoma. Conclusion: The diagnosis of Intestinal Lymphoma poses a diagnostic challenge for both developed and developing countries; however, coupling the risk factors with signs and symptoms can assist one in making a diagnosis. It is therefore important to always have a high index of suspicion, particularly for HIV patients with lymphadenopathy. Doi: 10.28991/SciMedJ-2023-05-01-05 Full Text: PDF

Primary Isolated Breast Lymphoma Presenting as Primary Breast Cancer with 18F-FDG PET/CT.

A 40-year-old woman with a palpable mass lesion in her right breast suggested as breast cancer was admitted to 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) unit for the metabolic characterization of the lesion and for the staging of the disease. The patient had no fever and no evidence of weight loss or night sweats. 18F-FDG PET/CT revealed an isolated solid mass lesion with increased 18F-FDG uptake in the upper outer quadrant of the right breast and increased 18F-FDG uptake in the lymph nodes of the right axilla suspected as primary breast cancer and its local lymph node metastasis. There was no other pathological 18F-FDG uptake in the whole body. Excisional biopsy histopathology revealed diffuse large B-cell non-Hodgkin lymphoma.

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.

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.