Long-term complete remission in a patient with high-risk primary mediastinal B-cell lymphoma and iatrogenic symptomatic bradycardia after only two courses of DA-EPOCH-R followed by chemo-free treatment.

Most patients with Primary Mediastinal B-Cell Lymphoma (PMBCL) are cured by rituximab and doxorubicin-based immunochemotherapy, with or without radiotherapy. In cases with relapsed and refractory (RR) disease the prognosis was historically poor. Recently, immune checkpoint-based strategies have been shown to be highly effective in patients with RR-PMBCL. We report the case of a 23-year-old woman who, due to recurring episodes of symptomatic chemotherapy-induced sinus bradycardia, was unable to receive the planned six courses of immunochemotherapy, mediastinal radiotherapy, and autologous transplantation, leading to the early initiation of a chemo-free strategy. The patient maintains a continuous complete remission at a four-year follow-up after only two cycles of immunochemotherapy followed by nivolumab plus brentuximab vedotin (BV) and pembrolizumab consolidation. Beyond describing an underreported complication of anticancer treatments, the favorable clinical outcome suggests that in PMBCL, a minimal load of chemotherapy, integrated by early PD-1 blockade, with or without BV, may be sufficient to achieve long-term disease control and cure at least in some patients.

The Health Impacts of Better Access to Axicabtagene Ciloleucel: The Case of Spain.

In this study, the health impacts of improving access to treatment with axicabtagene ciloleucel (axi-cel) was assessed in patients with relapsed/refractory diffuse large B-cell lymphoma after ≥2 lines of therapy in Spain. A partitioned survival mixture cure model was used to estimate the lifetime accumulated life years gained (LYG) and quality-adjusted life years (QALYs) per patient treated with axi-cel versus chemotherapy. Efficacy data were extracted from the ZUMA-1 trial for axi-cel and from the SCHOLAR-1 study for chemotherapy. In the base case, the incremental outcomes of axi-cel versus chemotherapy were evaluated in a cohort of 187 patients treated with CAR T-cell therapies, as reported by the "Spanish National Health System Plan for Advanced Therapies", and in the alternative scenario in the full eligible population based on epidemiological estimates (n = 490). Taking those currently treated with axi-cel, compared with chemotherapy, axi-cel provided an additional 1341 LYGs and 1053 QALYs. However, when all eligible patients (n = 490) were treated, axi-cel provided an additional 3515 LYs and 2759 QALYs. Therefore, if all eligible patients were treated with axi-cel rather than those currently treated as per the registry (n = 187), there would have been an additional 303 patients treated, resulting in an additional 2173 LYGs and 1706 QALYs in total. The lack of access in Spain has led to a loss of a substantial number of LYGs and QALYs, and efforts should be made to improve access for all eligible patients.

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.

Outcomes of Patients Treated With RCHOP With a PET-Adapted Approach for Consolidative Radiotherapy: A Retrospective Single-Center Study at the Royal Marsden Hospital.

BACKGROUND: Treatment with CHOP-based chemotherapy with consolidative radiotherapy (CRT) for primary mediastinal B cell lymphoma (PMBCL) has been the standard approach in the pre-rituximab era. Overtreatment with CRT for patients who may have already been cured by primary immunochemotherapy in the rituximab era is a significant concern due to the long-term toxicity associated with radiotherapy. Positron emission tomography (PET) may help to identify patients who may not benefit from further CRT. METHODS: We conducted a retrospective review of patients treated at the Royal Marsden Hospital between 2003 and 2020 for PMBCL to assess CRT use and survival outcomes. RESULTS: Forty-three patients were identified, with 95% of the patients receiving R-CHOP. CRT was given in 5 patients. Five-year event-free survival was 79% (95% confidence interval: 64%-89%) and 5-year overall survival was 88% (95% confidence interval: 73%-95%). Seven of 9 patients with DS4 did not receive CRT and instead monitored with serial PET scans. None of these 7 patients relapsed in the mediastinum. CONCLUSION: CRT may be omitted in patients with a negative end of treatment PET scans; however, careful observation may also obviate the need for CRT in PET positive patients.

[Primary mediastinal large B-cell lymphoma complicated with myotonic dystrophy].

A 39-year-old woman with myotonic dystrophy (DM) presented with syncope and was diagnosed with primary mediastinal large B-cell lymphoma, clinical stage IA. PET-CT revealed an upper mediastinal mass with high FDG uptake (SUVmax, 14.8). She had muscle weakness associated with DM, but her performance status was preserved. She was treated with 6 cycles of dose-adjusted EPOCH-R therapy and localized irradiation for the residual mass, without severe adverse events or recurrence of syncope. Patients with DM should be monitored for cardiac events and muscle weakness when undergoing lymphoma treatment.

Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies.

Introduction: Diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) are aggressive histological subtypes of non-Hodgkin's lymphoma. Improved understanding of the underlying molecular pathogenesis has led to new classification and risk stratification tools, including the development of cell-free biomarkers through liquid biopsies. The goal of this study was to investigate cell-free RNA (cfRNA) biomarkers in DLBCL and PMBCL patients. Materials and methods: Blood plasma samples (n=168) and matched diagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples (n=69) of DLBCL patients, PMBCL patients and healthy controls were collected between 2016-2021. Plasma samples were collected at diagnosis, at interim evaluation, after treatment, and in case of refractory or relapsed disease. RNA was extracted from 200 µl plasma using the miRNeasy serum/plasma kit and from FFPE tissue using the miRNeasy FFPE kit. RNA was subsequently sequenced on a NovaSeq 6000 instrument using the SMARTer Stranded Total RNA-seq pico v3 library preparation kit. Results: Higher cfRNA concentrations were demonstrated in lymphoma patients compared to healthy controls. A large number of differentially abundant genes were identified between the cell-free transcriptomes of DLBCL patients, PMBCL patients, and healthy controls. Overlap analyses with matched FFPE samples showed that blood plasma has a unique transcriptomic profile that significantly differs from that of the tumor tissue. As a good concordance between tissue-derived gene expression and the immunohistochemistry Hans algorithm for cell-of-origin (COO) classification was demonstrated in the FFPE samples, but not in the plasma samples, a 64-gene cfRNA classifier was developed that can accurately determine COO in plasma. High plasma levels of a 9-gene signature (BECN1, PRKCB, COPA, TSC22D3, MAP2K3, UQCRHL, PTMAP4, EHD1, NAP1L1 pseudogene) and a 5-gene signature (FTH1P7, PTMAP4, ATF4, FTH1P8, ARMC7) were significantly associated with inferior progression-free and overall survival in DLBCL patients, respectively, independent of the NCCN-IPI score. Conclusion: Total RNA sequencing of blood plasma samples allows the analysis of the cell-free transcriptome in DLBCL and PMBCL patients and demonstrates its unexplored potential in identifying diagnostic, cell-of-origin, and prognostic cfRNA biomarkers.

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

In recent years, lesbian, gay, bisexual, and transgender (LGBT) populations have been gaining acceptance in society. However, very few cases of malignancy in the LGBT population have been reported thus far. We herein report a transgender woman receiving estrogen supplementation who developed primary mediastinal large B-cell lymphoma (PMBCL) and was treated with dose-adjusted EPOCH-rituximab (DA-EPOCH-R) therapy. The patient achieved complete remission after the sixth course of DA-EPOCH-R therapy. To help this LGBT patient continue receiving chemotherapy smoothly on admission, adjusting the hospital environment, such as the allocation of rooms, was essential.

Central nervous system metastasis in a young female patient with primary mediastinal large B-cell lymphoma: A case report and literature review.

Background: Primary mediastinal B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma that originates from a B cell in the thymus. It usually affects young female. Case description: A 30-year-old woman presented with mediastinal mass with history of shortness of breath and chest pain. blood analysis showed low levels of hemoglobin, hematocrit, and mean corpuscular volume and high red cell distribution width. A computed tomography (CT)-guided mediastinal core biopsy disclosed primary mediastinal large B-cell lymphoma (PMLBL) with a nongerminal center phenotype and lung tissue infiltrate. Moreover, after undergoing six cycles of rituximab, cyclophosphamide, hydroxydaunomycin, Oncovin, and prednisone (R-CHOP) chemotherapy and mediastinal radiotherapy, the patient presented with headache and visual disturbance due to multiple supratentorial lesions. Conclusion: Till date, only a few cases of central nervous system (CNS) metastasis have been reported in the literature. Moreover, CNS metastasis of refractory PMBCL is an uncommon event with a poor prognosis. Brain metastases are often the ultimate fatal consequence of many aggressive cancers, so early detection and treatment are important.

Primary Mediastinal B-Cell Lymphoma in Children and Young Adults.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare but aggressive mature B-cell lymphoma that arises from thymic B cells and most commonly affects adolescents and young adults. PMBCL is now recognized by the WHO as a distinct entity from diffuse large B-cell lymphoma (DLBCL), not otherwise specified, with a unique clinical presentation and distinct morphologic features and molecular alterations. Similar to classic Hodgkin lymphoma, PMBCL tumors are characterized by alterations in the nuclear factor-κB and JAK/STAT pathways. These tumors also exhibit an immune evasion phenotype marked by upregulation of PD-L1 and loss of B2M. Historic data indicates that outcomes for pediatric patients with PMBCL are inferior compared with pediatric patients with DLBCL treated on the same protocols, and there is no current standard approach to initial treatment. Common regimens used for children with PMBCL include multiagent chemotherapy regimens designed for Burkitt lymphoma, such as Lymphomes Malins B (LMB)-based or Berlin-Frankfurt-Münster (BFM)-based chemotherapy ± rituximab. Based on initial data in adults showing excellent outcomes with the use of DA-EPOCH-R regimens, these regimens have also been adopted in pediatrics, although with mixed results. Novel agents are currently being studied in PMBCL with the goal of improving outcomes and reducing reliance on radiation and/or high-dose chemotherapy. Immune checkpoint blockade with PD-1 inhibition is of particular interest given the upregulation of PD-L1 in PMBCL and the known efficacy of these agents in the relapsed setting. Future efforts in PMBCL will also seek to determine the role of FDG-PET in evaluating response to therapy and the role of biomarkers in risk stratification.

Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study.

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting.Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined.Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured.Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity.

Development of primary mediastinal B-cell lymphoma (PMBL) is driven by cumulative genomic aberrations. We discovered a unique copy-neutral loss of heterozygosity (CN-LOH) landscape of PMBL which distinguishes this tumor from other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma. Using single nucleotide polymorphism array analysis we identified large-scale CN-LOH lesions in 91% (30/33) of diagnostic PMBLs and both investigated PMBL-derived cell lines. Altogether, the cohort showed 157 extra-large (25.3-248.4 Mb) CN-LOH lesions affecting up to 14 chromosomes per case (mean of 4.4) and resulting in a reduction of heterozygosity an average of 9.9% (range 1.3-51%) of the genome. Predominant involvement of terminal chromosomal segments suggests the implication of B-cell specific crossover events in the pathogenesis of PMBL. Notably, CN-LOH stretches non-randomly clustered on 6p (60%), 15 (37.2%), and 17q (40%), and frequently co-occurred with homozygous mutations in the MHC I (6p21), B2M (15q15), and GNA13 (17q23) genes, respectively, as shown by preliminary whole-exome/genome sequencing data. Altogether, our findings implicate CN-LOH as a novel and distinct mutational process contributing to the molecular pathogenesis of PMBL. The aberration acting as "second hit" in the Knudson hypothesis, ranks as the major mechanism converting to homozygosity the PMBL-related driver genes. Screening of the cohort of 199 B cell leukemia/lymphoma whole-genomes revealed significant differences in the CN-LOH landscape of PMBL and other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma.

Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) therapy has revolutionized the treatment of relapsed/refractory large B-cell lymphoma (LBCL). However, patients who are excluded or have no access to CAR-T represent a challenge for clinicians and have generally a dismal outcome. The landscape for this category of patients is constantly evolving: new agents have been approved in the last 2-3 years, alone or in combination, and novel treatment modalities are under investigation. AREAS COVERED: Thereafter, we reviewed the currently available therapeutic strategies: conventional chemotherapy, antibody-drug conjugate ADC (mainly polatuzumab and loncastuxumab), bispecific antibodies (CD19/CD3 and focus on novel CD20/CD3 Abs), immunomodulatory drugs (covering tafasitamab and lenalidomide, checkpoint inhibitors mainly in PMBL), small molecules (selinexor, BTK, and PI3K inhibitors), and the role of radiotherapy. EXPERT OPINION: Navigating this scenario will uncover new challenges, including identifying an ideal sequence for these therapies, the most effective combinations, and search for consistent predictive factors to help selecting the appropriate population of LBCL patients. At present, supporting clinical research for CAR-T ineligible patients, a new and challenging group, must remain a major focus that is complementary to advances in CAR T-cell therapy.

Prognostic significance of clinical characteristics and 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters in patients with primary mediastinal B-cell lymphoma.

OBJECTIVE: Primary mediastinal B-cell lymphoma (PMBCL) lacks standard treatment regimens. This study aimed to identify the disease's clinical features and prognostic factors. METHODS: This retrospective study included 56 patients with PMBCL. Patient demographic details and clinicopathological characteristics were summarized, and their effects on progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The median patient age was 29 years (range, 14-56). Twenty-two patients received DA-EPOCH-R (dose-adjusted etoposide, vincristine, and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone, as well as rituximab), and 34 patients received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Clinical/laboratory parameters, overall response rates, and 5-year PFS and OS rates did not differ between the treatment groups. Kaplan-Meier analysis indicated that late-stage disease and a higher International Prognostic Index (IPI) were associated with shorter PFS and OS. Furthermore, patients with B symptoms and first-line treatment non-responders exhibited worse OS. 18Fluorodeoxyglucose-positron emission tomography/computed tomography quantitative parameters, such as higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were corrected with shorter PFS. CONCLUSIONS: This study revealed that stage IV disease, higher IPI, and B symptoms were poor prognostic factors in patients with PMBCL. Significantly, higher MTV and TLG portended worse PFS.

Malignant Tracheoparenchymal Fistula in Primary Mediastinal B-Cell lymphoma detected on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Acquired tracheobronchial fistulas are a relatively uncommon complication. Among them, tracheo-mediastinal-parenchymal fistulas are particularly rare. Most of the reported cases are associated with concurrent chemoradiotherapy in lung cancer. It has not been reported in lymphomas. These fistulas are associated with high mortality due to infection and bleeding, and there is no consensus on a definitive optimal therapy. Here, we present a case of tracheoparenchymal fistula in a follow-up primary mediastinal B-cell lymphoma case. This case highlights the utility of fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the initial diagnosis and follow-up of lymphoma. The PET/CT could show demonstrate the residual disease and differentiate it from other therapy-related benign changes.

End of treatment FDG-PET in primary mediastinal B-cell lymphoma treated with R-chemotherapy: Prognostic indicator and implications for consolidation radiotherapy.

The ideal therapeutic regimen in primary mediastinal B-cell lymphoma (PMBCL) is controversial and may include consolidation radiotherapy (RT). An adequate strategy is essential in a population where long-term effects of RT are significant. We evaluated the prognostic value of end-of-treatment (EOT) FDG-PET in 50 patients receiving rituximab and anthracycline-containing chemotherapy and its implications for consolidative RT. Thirty patients (60%) obtained complete metabolic response (CMR), five received consolidation RT. The remaining patients had partial response (14) and progression (6). Of these, 12 received mediastinal RT, six salvage chemotherapy, and two no further treatment. Five-year progression free survival was 100% and 48% (95% CI 30%-77%) in patients with negative and positive EOT FDG-PET, respectively (P < .001). Five-year overall survival for negative and positive EOT FDG-PET was 100% and 67% (95% CI 48%-93%) respectively (P = .001). Within positive EOT FDG-PET cases, an association was found between Deauville score and survival. The negative predictive value (NPV) of EOT FDG-PET for disease relapse/progression was 100% (95% CI 0.88-1.00); the positive predictive value was 47% (95% CI 0.24-0.71). This study demonstrates the importance of metabolic assessment in PMBCL and is relevant for its high NPV. Our data favor the use of EOT FDG-PET for decisions concerning RT.

Dose-adjusted EPOCH-R is not superior to sequential R-CHOP/R-ICE as a frontline treatment for newly diagnosed primary mediastinal B-cell lymphoma: Results of a bi-center retrospective study.

PURPOSE: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Despite its aggressive course, PMBCL is considered curable. While in recent years dose-adjusted (DA) EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) has become widely endorsed as first-line therapy for newly-diagnosed PMBCL, the optimal treatment for this disease and the role of radiotherapy (RT) remains unclear. DA-EPOCH-R provides good clinical outcomes, albeit is associated with short- and long-term toxicity. To address this issue, the current retrospective bi-icenter analysis compared efficacy and toxicity of DA-EPOCH-R and a less toxic R-CHOP/R-ICE regimen used for the treatment of newly-diagnosed PMBCL. PATIENTS AND METHODS: The study included all patients with a histologically confirmed PMBCL diagnosis treated with DA-EPOCH-R or R-CHOP/R-ICE between 01/2013-12/2020 at two tertiary medical centers. Patient demographic and clinical data were derived from institutional electronic medical records. The analysis included 56 patients: 31 received DA-EPOCH-R and 25 - R-CHOP/R-ICE. RESULTS: At a median follow-up of 1.9 years (IQR 3.1 years), similar progression-free survival (2.1 versus 2.4 years; p = 0.7667), overall survival (2.5 versus 2.7 years; p = 0.8047) and complete response (80%) were observed in both groups. However, DA-EPOCH-R was associated with significantly longer hospitalization required for its administration (p < 0.001) and a trend for higher frequency of infections, stomatitis, thrombotic complications and febrile neutropenia-related hospitalizations. CONCLUSION: DA-EPOCH-R and R-CHOP/R-ICE provide similarly encouraging outcomes in newly-diagnosed PMBCL patients. R-CHOP/R-ICE is associated with lower toxicity and significantly reduced hospitalization. Our findings suggest that this regimen may be considered as an alternative to DA-EPOCH-R in this patient population.

Current and emerging treatment options in primary mediastinal B-cell lymphoma.

Previously considered a subtype of diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) is now recognized by the World Health Organization as an independent entity. PMBCL has clinicopathologic features that are separate from systemic DLBCL and harbors some biologic characteristics which overlap with nodular sclerosing classic Hodgkin's lymphoma (cHL). Similar to cHL, copy number alterations of 9p24.1 are frequently seen in PMBCL, which leads to increased expression of key genes in the region, including programmed death-ligand 1( PD-L1), PD-L2, and JAK2. In addition, PMBCL cells express CD30 in a mostly patchy fashion. In the upfront setting, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (i.e., DA-EPOCH-R) is the only regimen that has been shown in a prospective setting to result in outstanding outcomes without consolidative radiation to the mediastinum, with a 5-year event-free survival rate of 93% and overall survival rate of 97%. Thus, in recent years, DA-EPOCH-R has been recognized as the preferred frontline regimen. Despite the encouraging results in the frontline setting, the outcomes in the relapsed/refractory setting remain poor. The current approach of salvage chemotherapy followed by autologous stem cell transplantation, as used in patients with DLBCL, does not result in high rates of cure in patients with rrPMBCL. In recent years, the characteristic molecular features identified in PMBCL have provided more treatment opportunities for this patient population. In the relapsed setting, single-agent PD-1 inhibitor pembrolizumab have demonstrated high and durable remission rates. Despite the expression of CD30, the CD30 antibody drug-conjugate brentuximab vedotin (BV) as a single agent has been deemed inactive in this disease. On the contrary, the combinations of BV and PD-1 inhibitor have shown higher response rates than PD-1 inhibitor alone. Moreover, anti-CD19 chimeric antigen receptor T-cell (CAR T-cell) therapy has been positioned as another successful strategy for patients with rrPMBCL. Axicabtagene ciloleucel and lisocabtagene maraleucel are two products used in rrPMBCL.

Treatment of Primary Mediastinal B-Cell Lymphoma With R-CEOP (Rituximab, Cyclophosphamide, Etoposide, Vincristine, and Prednisone).

Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of non-Hodgkin's lymphoma. It typically has an aggressive behavior with potential clinical emergencies including cardiac tamponade, thrombosis of major neck vessels, airway obstruction, and tumor lysis syndrome. In this case report, a 38-year-old Caucasian male presented with shortness of breath, a two-month history of 40-pound weight loss, and a left-sided chest wall mass. CT imaging showed a mediastinal mass, measuring 13 × 14.6 × 8.6 cm3, with invasion and partial occlusion of the brachiocephalic veins and upper superior vena cava causing superior vena cava syndrome, and encasement of multiple coronary artery segments. CT-guided biopsy showed high-grade B-cell lymphoma. Cytology biomarkers were positive for CD20, CD45, and PAX5. A trans-thoracic echocardiogram (TTE) was obtained prior to chemotherapy initiation to establish a baseline for cardiac function, which showed an ejection fraction (EF) of 45-50%, right ventricle volume overload and dilation, and pulmonary hypertension. R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, and prednisone) chemotherapy regimen was initiated and a follow-up echocardiogram after three cycles, revealed a significant improvement in EF; the patient subsequently received three additional cycles of R-EPOCH. Current regimens in the United States utilize dose-adjusted R-EPOCH and R-CHOP, but they must be used cautiously in patients with compromised cardiac function, due to the cardiotoxic side effects of the chemotherapy agent, doxorubicin. This case illustrates that anthracycline-free regimens should be considered in patients with reduced cardiac function, with this case showing the utilization of an anthracycline-free regimen (R-CEOP) for the first three cycles, followed by a transition to R-EPOCH.

Pembrolizumab in the treatment of refractory primary mediastinal large B-cell lymphoma: safety and efficacy.

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rare subtype of lymphoma, clinically and biologically distinct from diffuse large B-cell lymphoma (DLBCL) that shows overlapping features with classical Hodgkin lymphoma (cHL). If first-line strategies lead to 80-85% of curability, relapse occurs early with a chemo-refractory disease and a poor outcome. The presence of 9p24.1 rearrangement, conducting to the overexpression of the immune checkpoint molecules PDL1 and 2, has paved the way for immune checkpoint blockers development in these entities. Pembrolizumab, an anti PD-1 checkpoint antibody, was initially approved in solid cancer and later on in the lymphoma field in cHL.Areas covered: We summarize the biology and clinical need in PMBL, leading to the rationale for checkpoint inhibitors development, as well as pembrolizumab clinical studies in this entity. To do so, we performed a PubMed search using the terms: 'PMBCL,' 'lymphoma,' 'Immune checkpoint,' and 'Pembrolizumab.'Expert opinion: Pembrolizumab showed tolerable safety profile and efficacy data in patients with PMBL who have relapsed after, or are ineligible for autologous stem cell transplant (ASCT). Some combination strategies have shown promising preliminary results, while others are currently being conducted.