Primary Mediastinal B-cell Lymphoma Research Articles

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Nivolumab combined with brentuximab vedotin with or without mediastinal radiotherapy for relapsed/refractory primary mediastinal large B-cell lymphoma.

Not available.

Glofitamab (Columvi)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses glofitamab (Columvi), concentrate for solution for infusion, 2.5 mg/2.5 mL vial and 10 mg/10 mL vial, IV infusion. Indication: For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, arising from follicular lymphoma (trFL), or primary mediastinal B-cell lymphoma (PMBCL), who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy.

Allogeneic Stem Cell Transplantation in Treatment of Refractory/Relapsed Lymphomas

Aim: To assess the outcome of allogeneic stem cell transplantation in patients with refractory/relapsed lymphoma. Methods: Between 2021 and 2023, 6 patients with refractory/relapsed (R/R) lymphoma underwent allogeneic stem cell transplantation at the Bone Marrow Transplant Department of Regional Institute of Oncology Iasi- 4 with Hodgkin lymphoma (HL), 1 with primary mediastinal large B-cell lymphoma (PMBCL) and 1 with Mycosis fungoides (MF). All patients received reduced intensity conditioning chemotherapy, combining Fludarabine, Busulfan or Melphalan. The prophylaxis of graft-versus-host-disease (GVHD) was made with Cyclophosphamide (n=4), Tacrolimus and Mycophenolate mofetil (n=5), Cyclosporine (n=1). Results: The post transplant evolution of the patients was marked by infectious complications (n=5), digestive mucositis (n=4) and viral reactivations (n=4). One patient with HL had acute cutaneous and hepatic graftversus-host disease(GVHD) and two had chronic hepatic and intestinal GVHD. Imaging evaluation by PETCT on day +100 shows a complete response in three patients with HL and progressive disease in the patient with PMBCL and one patient with HL. Conclusion: Despite the introduction of increasingly effective treatment options for R/R lymphoma, transplantation continues to play an important role in the management of these patients. Allogeneic transplantation is an effective therapy for advanced aggressive lymphoma, limited by treatment-related toxicity and mortality.

Semi-supervised learning towards automated segmentation of PET images with limited annotations: application to lymphoma patients.

Manual segmentation poses a time-consuming challenge for disease quantification, therapy evaluation, treatment planning, and outcome prediction. Convolutional neural networks (CNNs) hold promise in accurately identifying tumor locations and boundaries in PET scans. However, a major hurdle is the extensive amount of supervised and annotated data necessary for training. To overcome this limitation, this study explores semi-supervised approaches utilizing unlabeled data, specifically focusing on PET images of diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) obtained from two centers. We considered 2-[18F]FDG PET images of 292 patients PMBCL (n = 104) and DLBCL (n = 188) (n = 232 for training and validation, and n = 60 for external testing). We harnessed classical wisdom embedded in traditional segmentation methods, such as the fuzzy clustering loss function (FCM), to tailor the training strategy for a 3D U-Net model, incorporating both supervised and unsupervised learning approaches. Various supervision levels were explored, including fully supervised methods with labeled FCM and unified focal/Dice loss, unsupervised methods with robust FCM (RFCM) and Mumford-Shah (MS) loss, and semi-supervised methods combining FCM with supervised Dice loss (MS + Dice) or labeled FCM (RFCM + FCM). The unified loss function yielded higher Dice scores (0.73 ± 0.11; 95% CI 0.67-0.8) than Dice loss (p value < 0.01). Among the semi-supervised approaches, RFCM + αFCM (α = 0.3) showed the best performance, with Dice score of 0.68 ± 0.10 (95% CI 0.45-0.77), outperforming MS + αDice for any supervision level (any α) (p < 0.01). Another semi-supervised approach with MS + αDice (α = 0.2) achieved Dice score of 0.59 ± 0.09 (95% CI 0.44-0.76) surpassing other supervision levels (p < 0.01). Given the time-consuming nature of manual delineations and the inconsistencies they may introduce, semi-supervised approaches hold promise for automating medical imaging segmentation workflows.

Chinese expert consensus on the diagnosis and management of primary mediastinal large B-cell lymphoma (2024)

Primary mediastinal large B-cell lymphoma (PMBL) is an aggressive B-cell lymphoma that is thought to arise from thymic (medullary) B cells and has unique clinicopathologic and molecular features. In recent years, the understanding of the pathogenesis and treatment of PMBL has been updated to varying degrees, particularly in the area of new drug therapy. In order to improve the diagnosis and treatment of PMBL in China, the Lymphocyte Disease Group of the Chinese Medical Association (CMA) and the Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology (CSCO) commissioned a group of experts to formulate this consensus.

Axicabtagene ciloleucel treatment is more effective in primary mediastinal large B-cell lymphomas than in diffuse large B-cell lymphomas: the Italian CART-SIE study

Axicabtagene ciloleucel showed efficacy for relapsed/refractory large B-cell lymphomas (LBCL), including primary mediastinal B-cell lymphomas (PMBCL); however, only few PMBCLs were reported. Aim was to evaluate efficacy and safety of axicabtagene ciloleucel in patients with PMBCL compared to those with other LBCL, enrolled in the Italian prospective observational CART-SIE study. PMBCLs (n = 70) were younger, with higher percentage of bulky and refractory disease, compared to other LBCLs (n = 190). Median follow-up time for infused patients was 12.17 months (IQR 5.53,22.73). The overall (complete + partial) response rate (ORR,CR + PR) after bridging was 41% for PMBCL and 28% for other LBCL, p = 0.0102. Thirty days ORR was 78% (53/68) with 50% (34) CR in PMBCL, and 75% (141/187) with 53% (100) CR in other LBCL, p = 0.5457. Ninety days ORR was 69% (45/65) with 65% (42) CR in PMBCL, and 54% (87/162) with 47% (76) CR in other LBCL; progressive disease was 21% in PMBCL and 45% in other LBCL, p = 0.0336. Twelve months progression-free survival was 62% (95% CI: 51–75) in PMBCL versus 48% (95% CI: 41–57) in other LBCL, p = 0.0386. Twelve months overall survival was 86% (95% CI: 78–95) in PMBCL versus 71% (95% CI: 64–79) in other LBCL, p = 0.0034. All grade cytokine release syndrome was 88% (228/260); all grade neurotoxicity was 34% (88/260), with 6% of fatal events in PMBCL. Non-relapse mortality was 3%. In conclusion, PMBCLs achieved significantly better response and survival rates than other LBCLs.

Evaluating Outcome Prediction via Baseline, End-of-Treatment, and Delta Radiomics on PET-CT Images of Primary Mediastinal Large B-Cell Lymphoma.

Accurate outcome prediction is important for making informed clinical decisions in cancer treatment. In this study, we assessed the feasibility of using changes in radiomic features over time (Delta radiomics: absolute and relative) following chemotherapy, to predict relapse/progression and time to progression (TTP) of primary mediastinal large B-cell lymphoma (PMBCL) patients. Given the lack of standard staging PET scans until 2011, only 31 out of 103 PMBCL patients in our retrospective study had both pre-treatment and end-of-treatment (EoT) scans. Consequently, our radiomics analysis focused on these 31 patients who underwent [18F]FDG PET-CT scans before and after R-CHOP chemotherapy. Expert manual lesion segmentation was conducted on their scans for delta radiomics analysis, along with an additional 19 EoT scans, totaling 50 segmented scans for single time point analysis. Radiomics features (on PET and CT), along with maximum and mean standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), tumor dissemination (Dmax), total lesion glycolysis (TLG), and the area under the curve of cumulative standardized uptake value-volume histogram (AUC-CSH) were calculated. We additionally applied longitudinal analysis using radial mean intensity (RIM) changes. For prediction of relapse/progression, we utilized the individual coefficient approximation for risk estimation (ICARE) and machine learning (ML) techniques (K-Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA), and Random Forest (RF)) including sequential feature selection (SFS) following correlation analysis for feature selection. For TTP, ICARE and CoxNet approaches were utilized. In all models, we used nested cross-validation (CV) (with 10 outer folds and 5 repetitions, along with 5 inner folds and 20 repetitions) after balancing the dataset using Synthetic Minority Oversampling TEchnique (SMOTE). To predict relapse/progression using Delta radiomics between the baseline (staging) and EoT scans, the best performances in terms of accuracy and F1 score (F1 score is the harmonic mean of precision and recall, where precision is the ratio of true positives to the sum of true positives and false positives, and recall is the ratio of true positives to the sum of true positives and false negatives) were achieved with ICARE (accuracy = 0.81 ± 0.15, F1 = 0.77 ± 0.18), RF (accuracy = 0.89 ± 0.04, F1 = 0.87 ± 0.04), and LDA (accuracy = 0.89 ± 0.03, F1 = 0.89 ± 0.03), that are higher compared to the predictive power achieved by using only EoT radiomics features. For the second category of our analysis, TTP prediction, the best performer was CoxNet (LASSO feature selection) with c-index = 0.67 ± 0.06 when using baseline + Delta features (inclusion of both baseline and Delta features). The TTP results via Delta radiomics were comparable to the use of radiomics features extracted from EoT scans for TTP analysis (c-index = 0.68 ± 0.09) using CoxNet (with SFS). The performance of Deauville Score (DS) for TTP was c-index = 0.66 ± 0.09 for n = 50 and 0.67 ± 03 for n = 31 cases when using EoT scans with no significant differences compared to the radiomics signature from either EoT scans or baseline + Delta features (p-value> 0.05). This work demonstrates the potential of Delta radiomics and the importance of using EoT scans to predict progression and TTP from PMBCL [18F]FDG PET-CT scans.

Prognostic factors and clinical survival outcome in patients with primary mediastinal diffuse large B-cell lymphoma in rituximab era: A population-based study.

The goal of this study was to investigate the clinical characteristics, prognostic variables, and survival of patients with primary mediastinal diffuse large B cell lymphoma (PMBCL) in the rituximab era. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PMBCL patients diagnosed between 2000 and 2019. The Kaplan-Meier (K-M) technique and log-rank test were used to assess overall survival (OS) and disease-specific survival (DSS). The independent prognostic variables for OS and DSS were identified using univariate and multivariate Cox regression analysis. Nomograms were created to predict survival prospects according to identified prognostic indicators. Totally, 841 patients were enrolled with PMBCL. One-year, 5-year, and 10-year OS rates were 93.99%, 85.04%, and 81.76%, and the corresponding DSS rates were 95.27%, 87.37%, and 85.98%. The results of multivariate Cox regression analysis demonstrated that age, years of diagnosis, Ann arbor staging, and chemotherapy were independent prognostic factors for survival. Nomograms designed exclusively for PMBCL were created to forecast the likelihood of 1-year, 5-year, and 10-year OS and DSS, respectively. The Harrell concordance index (C-index) for the nomograms predictions of OS and DSS were 0.704 and 0.733, respectively, which showed the established model harboring powerful and accurate performance. The present study revealed that incidence of PMBCL has been consistently rising over the last 20 years. Simultaneously, survival rates have improved tremendously. Rituximab based immunochemotherapy has emerged as an effective treatment option, leading to enhanced OS and DSS outcomes. Furthermore, the nomograms specifically developed for PMBCL have demonstrated robustness and accuracy in forecasting OS and DSS rates at 1, 5, and 10 years. These predictive tools can be valuable for clinicians in accurately estimating prognosis and establishing personalized treatment plans and follow-up protocols.

Glofitamab (Columvi)

&#x0D; CADTH recommends that Columvi be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from follicular lymphoma (trFL), or primary mediastinal B-cell lymphoma (PMBCL), who have received 2 or more lines of systemic therapy and are ineligible to receive or cannot receive CAR-T cell therapy or have previously received CAR-T cell therapy if certain conditions are met.&#x0D; Columvi should only be covered to treat adult patients who have DLBCL not otherwise specified, trFL, or PMBCL that has come back or that did not respond to 2 or more previous treatments for their cancer, and who have also previously received CAR-T cell therapy, declined CAR-T cell therapy, or cannot receive CAR-T cell therapy.&#x0D; Columvi should only be reimbursed for a maximum of 12 treatment cycles, after a single dose of obinutuzumab to reduce the risk of cytokine release syndrome (CRS) and should not be given in combination with other anticancer drugs. Reimbursement of Columvi should be discontinued if a patient’s cancer grows or spreads or if treatment is unacceptably toxic to the patient. Columvi should only be reimbursed when prescribed by specialists with experience managing DLBCL, and if its cost is reduced.&#x0D;

Progress in treatment of primary mediastinal large B-cell lymphoma

Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive B-cell lymphoma originating from the thymus, which has different clinical and biological characteristics from diffuse large B-cell lymphoma, NOS. PMBCL tends to occur in young women, usually presenting as a large anterior mediastinal mass. Most patients are in stage Ⅰ-Ⅱ at the time of presentation. There is no standard prognostic scoring system for PMBCL. Immunochemotherapy is commonly used in the treatment of PMBCL, but the optimal first-line treatment has not been determined, and the status of radiotherapy is controversial. The value of PET-CT guided therapy needs to be further verified. Relapsed/refractory PMBCL has a poor prognosis, while novel therapies such as PD-1 inhibitors, brentuximab vedotin, and CAR-T can help improve survival in these patients.

Successful Treatment of Primary Mediastinal Large B-cell Lymphoma with DA-EPOCH-Rituximab Therapy in a Transgender Woman

Successful Treatment of Primary Mediastinal Large B-cell Lymphoma with DA-EPOCH-Rituximab Therapy in a Transgender Woman

Primary Mediastinal B-cell Lymphoma in Two Male Patients

Abstract Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of lymphoma with female predominance. Lymphomas are divided into Hodgkin’s lymphoma (accounts for 10% of all lymphomas) and nonHodgkin’s lymphoma. Pulmonologist often comes across lymphoma which can present as a mediastinal mass. PMBCL is an example of such a condition which represents 2%–3% of nonHodgkin lymphoma cases. This case report is about two male patients with PMBCL who presented with mediastinal mass, which was diagnosed by histopathological examination.

Relapse of primary mediastinal B-cell lymphoma with isolated central nervous system involvement: risk factors and search for personalized therapy

Relapse of primary mediastinal B-cell lymphoma with isolated central nervous system involvement: risk factors and search for personalized therapy

Myocardial Infiltration in Primary Mediastinal B-Cell Lymphoma Detected by Cardiac Magnetic Resonance Imaging

Introduction: Cardiac involvement, particularly myocardial infiltration in primary mediastinal lymphoma, is a rare occurrence with an incidence of only 9% in known cases of primary malignancy. Neoplasm infiltration into the myocardium manifests through direct invasion, hematogenous spread, transvenous invasion through the great veins, or lymphangitic spreading in the mediastinal. Myocardial infiltration in lymphoma presents a grim prognosis and its treatment may be associated with specific risks, such as myocardial rupture. Various imaging modalities may detect cardiac involvement, with cardiac magnetic resonance (CMR) imaging considered the gold standard. CMR enables clear delineation of myocardial infiltration, making it valuable for local staging, pretreatment planning, and evaluating treatment response. Case Presentation: : A 37-year-old woman patient was diagnosed with primary mediastinal large B-cell lymphoma. Mild chest discomfort and shortness of breath were observed 3 months before hospital admission. A thorax CT scan showed a heterogeneous contrast-enhancing mass with a central necrotic area in the anterior mediastinum. Following thoracotomy and tumor debulking, the patient complained of severe crushing chest pain radiating to her back, accompanied by new T wave inversion on ECG and elevated cardiac troponin levels a week after surgery. Coronary angiogram results showed a normal coronary artery. Subsequent cardiac MRI showed tumor infiltration into the anterior pericardial space, as well as the myocardium of the left and right ventricles. Chemotherapy was promptly initiated, resulting in a gradual improvement of symptoms. Conclusions: In this study, we discuss the use of 3D-CRT in the re-irradiation of NPC with its limitation on obtaining optimum dose sculpture compared to more sophisticated and widely spread modalities like IMRT. However, with careful planning, we can still obtain optimum tumor dose, minimize OAR dose, and subsequently late toxicities that come after. We hope that this study can bring hope to centers with limited facilities, and we suggest further studies on reirradiation, especially in OAR dose tolerance guidelines.

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.

Тактика ведения пациента с первичной медиастинальной В-крупноклеточной лимфомой, сопряженной с коронавирусной инфекцией, вызванной SARS-CoV-2: собственное клиническое наблюдение

Коронавирусная инфекция (COVID-19) – это острое респираторное заболевание, вызванное вирусом SARS-CoV-2, впервые было отмечено в городе Ухань (Китай) и быстро распространилось по всему миру. В условиях пандемии COVID-19 проведение специфического противоопухолевого лечения у пациентов с агрессивными В-клеточными лимфомами стало одной из сложных задач. Проведение специфической противоопухолевой терапии пациентов с гемобластозами, в том числе с агрессивными лимфопролиферативными заболеваниями, требует безотлагательного начала. Отсрочка специфической терапии может привести к прогрессированию лимфомы. Выбирая протокол химиотерапевтического режима, необходимо учитывать риск реактивации COVID-19 на фоне миелотоксической аплазии костномозгового кроветворения, а также дополнительного присоединения бактериальной и грибковой инфекции. Подтвержденная коронавирусная инфекция не должна быть противопоказанием к химиотерапии. В данной публикации представлены собственное клиническое наблюдение течения COVID-19 у пациента с первичной медиастинальной В-клеточной лимфомой на этапе химиотерапевтического лечения, а также выбор режима противоопухолевой терапии. Coronavirus disease (COVID-19) is an acute respiratory disease caused by the SARS-CoV-2 virus, was discovered first in Wuhan (China) and quickly spread throughout the world. Specific antitumor treatment in patients with aggressive B-cell lymphomas has become one of the most challenging issues in the context of the COVID-19 pandemic. An immediate start of specific antitumor therapy for patients with hematological malignancies including aggressive lymphoproliferative diseases (LPD) is required. The delay of specific therapy may lead to progression of lymphoma. It is necessary to consider the risk of reactivation of COVID-19 due to myelotoxic aplasia of bone marrow hematopoiesis, as well as further development of bacterial and fungal infections when choosing a chemotherapy regimen protocol. Confirmed COVID-19 infection should not be a contraindication for chemotherapy. This publication presents our own clinical experience of COVID-19 infection case in a patient with primary mediastinal B-cell lymphoma at chemotherapy treatment stage, as well as the choice of tactics for the antitumor therapy regimen.

Major impact of prognosis by age and sex in patients with primary mediastinal large B‑cell lymphoma.

The effective prognostic factors for primary mediastinal large B-cell lymphoma (PMLBCL) vary among published studies. The aim of the present study was to explore the factors influencing the overall survival (OS) and progression-free survival (PFS) of patients with PMLBCL at a single institute in Taiwan. This retrospective study was conducted to analyze the prognostic impact of age, sex, disease stage, International Prognostic Index (IPI) score, treatment modality and initial response. A total of 72 patients with a median age of 28 years were included in the study. The mean OS and PFS were 171.40 and 159.77 months, respectively. Female sex, age ≤60 years, receiving radiotherapy (RT) and achieving a complete response were found to be associated with a significantly improved OS and PFS. In addition, high-intensity chemotherapy and an IPI score ≤1 were associated with longer OS, and early-stage disease was associated with a PFS superior to that of advanced-stage disease. The predictive value of IPI is limited in PMLBCL. Therefore, it is necessary to develop a novel prognostic system. The present study revealed the impact of sex on prognosis and, therefore, this factor should be considered in future prognostic evaluations. Since a complete post-treatment response was found to be important, high-intensity chemotherapy is recommended. However, low-intensity treatment followed by RT consolidation appears to be a feasible approach in elderly patients.

Genetic Characterization of Primary Mediastinal B-Cell Lymphoma: Pathogenesis and Patient Outcomes.

Primary mediastinal large B-cell lymphoma (PMBCL) is a rare aggressive lymphoma predominantly affecting young female patients. Large-scale genomic investigations and genetic markers for risk stratification are lacking. To elucidate the full spectrum of genomic alterations, samples from 340 patients with previously untreated PMBCL were investigated by whole-genome (n = 20), whole-exome (n = 78), and targeted (n = 308) sequencing. Statistically significant prognostic variables were identified using a multivariable Cox regression model and confirmed by L1/L2 regularized regressions. Whole-genome sequencing revealed a commonly disrupted p53 pathway with nonredundant somatic structural variations (SVs) in TP53-related genes (TP63, TP73, and WWOX) and identified novel SVs facilitating immune evasion (DOCK8 and CD83). Integration of mutation and copy-number data expanded the repertoire of known PMBCL alterations (eg, ARID1A, P2RY8, and PLXNC1) with a previously unrecognized role for epigenetic/chromatin modifiers. Multivariable analysis identified six genetic lesions with significant prognostic impact. CD58 mutations (31%) showed the strongest association with worse PFS (hazard ratio [HR], 2.52 [95% CI, 1.50 to 4.21]; P < .001) and overall survival (HR, 2.33 [95% CI, 1.14 to 4.76]; P = .02). IPI high-risk patients with mutated CD58 demonstrated a particularly poor prognosis, with 5-year PFS and OS rates of 41% and 58%, respectively. The adverse prognostic significance of the CD58 mutation status was predominantly observed in patients treated with nonintensified regimens, indicating that dose intensification may, to some extent, mitigate the impact of this high-risk marker. By contrast, DUSP2-mutated patients (24%) displayed durable responses (PFS: HR, 0.2 [95% CI, 0.07 to 0.55]; P = .002) and prolonged OS (HR, 0.11 [95% CI, 0.01 to 0.78]; P = .028). Upon CHOP-like treatment, these patients had very favorable outcome, with 5-year PFS and OS rates of 93% and 98%, respectively. This large-scale genomic characterization of PMBCL identified novel treatment targets and genetic lesions for refined risk stratification. DUSP2 and CD58 mutation analyses may guide treatment decisions between rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.

OP79 Gene Expression Profiling In The Diagnosis Of Aggressive Large B Cell Lymphoma: An Early Exploratory Economic Evaluation

IntroductionThe addition of gene expression profiles (GEP) to the current clinicopathological diagnosis of aggressive large B cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempoSeq technology to distinguish Burkitt Lymphoma (BL) and Primary Mediastinal Large B Cell lymphoma (PMBCL) from Diffuse Large B Cell Lymphoma (DLBCL). This study aims to inform developers about the potential impact of the test on costs and health outcomes, and pricing and evidence generation strategies.MethodsDecision models compared current diagnosis with current plus GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from the literature and based on assumptions. Threshold estimates were made of the maximum price of the test and impact of incorrect disease classification using a threshold of GDP30,000 (USD37,155) per Quality Adjusted Life year (QALY). One way sensitivity analysis was conducted.ResultsAt base case values the BL signature delivers incremental QALYs of 0.0249 at an additional cost per patient of GBP508 (USD629). This results in a net monetary benefit (NMB) of GBP239 (USD296). The PMBCL signature delivers 0.0011 QALYs, a cost saving of GBP202 (USD250) and an NMB of GBP236 (USD292). The maximum threshold price for a combined test to be cost effective is GBP776 (USD961) (base case GBP400 (USD495)). Results are sensitive to cost differences in first line treatments and impact of false diagnoses.ConclusionsA combined test could be cost-effective in a UK context at a price around GBP750 (USD929). The developers can use this estimate to inform return on investment calculations. The number of patients who were reclassified as a result of the addition of GEP in our model was taken from small retrospective studies and the impact of false diagnoses was based on limited evidence. If the developers choose to proceed with the development, these aspects should be incorporated in evidence generation strategies.