Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis.

Introduction: Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies. Methods: We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution. Results: Two-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL. Discussion: Our study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection.

SOHO State-of-the-Art Updates and Next Questions: A Modern Approach to the Systemic Treatment of Advanced CTCL.

The term cutaneous T-cell lymphoma (CTCL) is a general term for T-cell lymphomas that are found primarily in skin. The most common CTCL entities, mycosis fungoides and Sezary syndrome are incurable diseases with a plethora of conventional treatment options. In the past treatment options have been selected primarily according to stage. Given newer targeted therapies with varied response in different body compartments, we suggest a compartment-guided algorithm that may enhance response rates directing the selection of the most efficacious treatment options.

Identifying unmet needs and challenges in the definition of a plaque in mycosis fungoides: An EORTC-CLTG/ISCL survey.

BACKGROUND: Consensus about the definition and classification of 'plaque' in mycosis fungoides is lacking. OBJECTIVES: To delineate a comprehensive view on how the 'plaque' entity is defined and managed in clinical practice; to evaluate whether the current positioning of plaques in the TNMB classification is adequate. METHODS: A 12-item survey was circulated within a selected panel of 22 experts (pathologists, dermatologists, haematologists and oncologists), members of the EORTC and International Society for Cutaneous Lymphoma. The questionnaire discussed clinical and histopathological definitions of plaques and its relationship with staging and treatment. RESULTS: Total consensus and very high agreement rates were reached in 33.3% of questions, as all panellists regularly check for the presence of plaques, agree to evaluate the presence of plaques as a potential separate T class, and concur on the important distinction between plaque and patch for the management of early-stage MF. High agreement was reached in 41.7% of questions, since more than 50% of the responders use Olsen's definition of plaque, recommend the distinction between thin/thick plaques, and agree on performing a biopsy on the most infiltrated/indurated lesion. High divergence rates (25%) were reported regarding the possibility of a clinically based distinction between thin and thick plaques and the role of histopathology to plaque definition. CONCLUSIONS: The definition of 'plaque' is commonly perceived as a clinical entity and its integration with histopathological features is generally reserved to specific cases. To date, no consensus is achieved as for the exact definition of thin and thick plaques and current positioning of plaques within the TNMB system is considered clinically inadequate. Prospective studies evaluating the role of histopathological parameters and other biomarkers, as well as promising diagnostic tools, such as US/RM imaging and high-throughput blood sequencing, are much needed to fully integrate current clinical definitions with more objective parameters.

R-CHOP Vs DA-EPOCH-R for Double-Expressor Lymphoma: A University of California Hematologic Malignancies Consortium Retrospective Analysis.

BACKGROUND: Managing double-expressor lymphomas (DEL) is controversial given the dearth of data and lack of standardized guidelines on this high-risk subset of lymphomas. No prospective and few retrospective studies limited by either their sample size or short follow-up address the question of initial treatment of choice for DEL. We performed the largest analysis to date exploring R-CHOP vs DA-EPOCH-R in DEL. METHODS: Adults with DEL diagnosed from 6/2012-2/2021 at 4 unique sites were retrospectively analyzed. Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints include overall survival (OS), overall and complete response rates (ORR and CRR), cumulative incidence of relapse, and autologous hematopoietic cell transplantation (autoHCT) utilization. RESULTS: 155 patients were included, 61 treated with R-CHOP and 94 with DA-EPOCH-R. 3-year PFS and OS were similar between R-CHOP and DA-EPOCH-R, 33.2% vs 57.2%,(P = .063), and 72.2% vs 71.6% (P = .43) after median follow-up times of 2.43 and 2.89 years, respectively. Patients <65 had improved PFS with DA-EPOCH-R, hazard ratio 0.41 (P = .01). CRR and ORR rates were also similar. Relapse rates were not statistically different, 51.9% vs 28.6% (P = .069). AutoHCT utilization was higher with R-CHOP vs DA-EPOCH-R, 23.0% vs 8.5% (P = .017). CONCLUSIONS: Our findings do not support the use of DA-EPOCH-R over R-CHOP for DEL. Patients <65 years may experience longer PFS with DA-EPOCH-R, but limitations to the analysis make this interpretation difficult.

Rare case of leptomeningeal small lymphocytic lymphoma with TP53 mutation detected by deep next-generation sequencing.

Involvement of the central nervous system (CNS) is an exceedingly rare presentation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), with no consensus on the optimal therapy. Here we describe a 71-year-old man with a skull-base leptomeningeal mass consistent with SLL on biopsy. Malignant cells were observed in the cerebrospinal fluid (CSF), but not in the peripheral blood, bone marrow, or other extramedullary sites. Molecular analysis of the patient's disease by next generation sequencing (NGS) detected no pathogenic mutations in 111 genes, with the exception of two low allele frequency variants identified during deep NGS analysis of TP53. The patient was treated with six cycles of high-dose methotrexate and systemic/intrathecal rituximab followed by venetoclax monotherapy, with complete resolution of CSF disease and radiographic decrease in size of the skull base lesion.

Characteristics and Outcome of Extranodal NK/T-cell Lymphoma in North America: A Retrospective Multi-Institutional Experience.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) is rare and clinical data from non-Asian countries are lacking. It is unclear whether outcomes and disease natural history is similar to reported Asian series. We assessed characteristics and outcomes of patients with ENKTL from major North American centers. PATIENTS AND METHODS: We retrospectively identified patients with newly-diagnosed CD56 + ENKTL and studied disease characteristics and clinical outcomes. RESULTS: One hundred and twenty-one patients with ENKTL diagnosed between June 1990 and November 2012 were identified. Eighty-three patients (69%) had stage I/II disease and were treated with combined modality therapy (CMT) (n = 53), chemotherapy alone (CT) (n = 14) or radiotherapy alone (RT) (n = 16).  Thirty-eight patients (31%) had stage III/IV disease and were treated with CMT (n = 12), CT (n = 23), or RT (n = 3).  The median follow-up for the entire cohort was 51 months. Patients with stage I/II disease, compared to those with stage III/IV disease, had superior 2-year progression free survival (PFS) 43% vs 19% (P = .03) and overall survival (OS) 59% vs. 29% (P= .004). Outcomes were similar for stage I/II patients who received CMT vs. RT alone with 2-year PFS (53% vs. 47%; P= .91) and OS (67% vs. 67%; P= .58). No significant differences in outcomes were noted based on race/ethnicity. CONCLUSIONS: This series represents a large experience of ENKTL treated at several major North American academic centers.  Our data are consistent with Asian studies: (1) majority of patients present with early-stage disease; (2) overall poor outcome regardless of race/ethnicity; (3) CMT likely yields favorable outcomes for suitable candidates with early-stage disease.

Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Characteristics and Outcome of Extranodal NK/T-Cell Lymphoma in North America: A Retrospective Multi-Institutional Experience.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) is rare and clinicaldata from non-Asian countries are lacking. It is unclear whether outcomes and diseasenatural history is similar to reported Asian series. We assessed characteristics and outcomes of patients with ENKTL from major North American centers. PATIENTS AND METHODS: We retrospectively identified patients with newly-diagnosedCD56 + ENKTL and studied disease characteristics and clinical outcomes. RESULTS: 121 patients with ENKTL diagnosed between June 1990 and November 2012 were identified. Eighty-three patients (69%) had stage I/II disease and were treatedwith combined modality therapy (CMT) (n=53), chemotherapy alone (CT) (n=14) orradiotherapy alone (RT) (n=16). Thirty-eight patients (31%) had stage III/IV diseaseand were treated with CMT (n=12), CT (n=23), or RT (n=3). The median follow-up forthe entire cohort was 51 months. Patients with stage I/II disease, compared to thosewith stage III/IV disease, had superior 2-year progression free survival (PFS) 43% vs19% (p=0.03) and overall survival (OS) 59% vs 29% (p=0.004). Outcomes were similarfor stage I/II patients who received CMT vs RT alone with 2-year PFS (53% vs 47%;p=0.91) and OS (67% vs 67%; p=0.58). No significant differences in outcomes werenoted based on race/ethnicity. CONCLUSIONS: This series represents a large experience of ENKTL treated at several major North American academic centers. OUR DATA ARE CONSISTENT WITH ASIAN STUDIES: 1) majority of patients present with early-stage disease; 2) overall poor outcome regardless of race/ethnicity; 3) CMT likely yields favorable outcomes for suitable candidates with early-stage disease.

Aggressive CD5-Positive Primary Bone Marrow Diffuse Large B-Cell Lymphoma with Leukemic Presentation.

Primary bone marrow diffuse large B-cell lymphoma is an exceedingly rare form of non-Hodgkin lymphoma. It may demonstrate a leukemic presentation, and a proportion of cases have CD5 expression. The prognostic implications of this CD5-positivity remain unknown. Here, we present a 78-year-old man who presented with circulating peripheral blood lymphoma cells and a hypercellular marrow involved by diffuse large B-cell lymphoma, germinal center B-cell subtype. The patient responded favorably to six cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and intrathecal methotrexate. He unfortunately relapsed in several enlarged inguinal lymph nodes and succumbed to the lymphoma approximately one year after diagnosis, demonstrating the particularly aggressive clinical course of his disease.

Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician's choice in cutaneous T-cell lymphoma: final data.

The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.

Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis.

INTRODUCTION: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study. METHODS: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30min < 10% (≥1 biopsy with <10% CD30 expression), or CD30min ≥ 10% (all biopsies with ≥10% CD30 expression) and baseline LCT present or absent. Efficacy analyses were the proportion of patients with objective response lasting ≥4 months (ORR4) and progression-free survival (PFS). RESULTS: Clinical activity with brentuximab vedotin was observed across all CD30 expression levels in patients with ≥1 biopsy showing ≥10% CD30 expression. Superior ORR4 was observed with brentuximab vedotin versus physician's choice in patients: with CD30min < 10% (40.9% versus 9.5%), with CD30min ≥ 10% (57.1% versus 10.3%), with LCT (64.7% versus 17.6%) and without LCT (38.7% versus 6.5%). Brentuximab vedotin improved median PFS versus physician's choice in patients: with CD30min < 10% (16.7 versus 2.3 months), with CD30min ≥ 10% (15.5 versus 3.9 months), with LCT (15.5 versus 2.8 months) and without LCT (16.1 versus 3.5 months). Safety profiles were generally comparable across subgroups. CONCLUSION: These exploratory analyses demonstrated that brentuximab vedotin improved rates of ORR4 and PFS versus physician's choice in patients with CD30-positive MF and ≥1 biopsy showing ≥10% CD30 expression, regardless of LCT status. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01578499.

Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Slows DLBCL Tumor Cell Growth In Vitro and In Vivo.

PURPOSE: miRNA-155 is an oncogenic miRNA highly expressed in B-cell malignancies, particularly in the non-germinal center B-cell or activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL. EXPERIMENTAL DESIGN: Preclinical studies included the delivery of cobomarsen to highly miR-155-expressing ABC-DLBCL cell lines to assess any phenotypic changes, as well as intravenous injections of cobomarsen in NSG mice carrying ABC-DLBCL xenografts, to study tumor growth and pharmacodynamics of the compound over time. To begin to test its safety and therapeutic efficacy, a patient was recruited who underwent five cycles of cobomarsen treatment. RESULTS: Cobomarsen decreased cell proliferation and induced apoptosis in ABC-DLBCL cell lines. Intravenous administration of cobomarsen in a xenograft NSG mouse model of ABC-DLBCL reduced tumor volume, triggered apoptosis, and derepressed direct miR-155 target genes. Finally, the compound reduced and stabilized tumor growth without any toxic effects for the patient. CONCLUSIONS: Our findings support the potential therapeutic application of cobomarsen in ABC-DLBCL and other types of lymphoma with elevated miR-155 expression.

Strategies for aggressive T-cell lymphoma: divide and conquer.

The aggressive peripheral T-cell lymphomas (PTCLs) are a heterogenous group of uncommon lymphomas of mature T lymphocytes dominated by 3 subtypes: systemic anaplastic large-cell lymphoma, both anaplastic lymphoma kinase positive and negative; nodal PTCL with T-follicular helper phenotype; and PTCL, not otherwise specified. Although the accurate diagnosis of T-cell lymphoma and the subtyping of these lymphomas may be challenging, there is growing evidence that knowledge of the subtype of disease can aid in prognostication and in the selection of optimal treatments, in both the front-line and the relapsed or refractory setting. This report focuses on the 3 most common subtypes of aggressive PTCL, to learn how current knowledge may dictate choices of therapy and consultative referrals and inform rational targets and correlative studies in the development of future clinical trials. Finally, I note that clinical-pathologic correlation, especially in cases of T-cell lymphomas that may present with an extranodal component, is essential in the accurate diagnosis and subsequent treatment of our patients.

Spotlight on Mogamulizumab-Kpkc for Use in Adults with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome: Efficacy, Safety, and Patient Selection.

Advanced cutaneous T cell lymphomas (CTCL) including mycosis fungoides (MF) and Sézary syndrome (SS) are often difficult to manage once they become resistant to initial systemic treatment. Current systemic treatments usually provide a limited duration of disease control, leaving this an area in desperate need of new treatment options for better long-term control. These conditions often affect the older population where transplantation may not be a feasible option. Recent studies evaluated a novel CCR4 humanized monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, which show a meaningful progression free survival (PFS) benefit. In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. Approval was based on the Phase III MAVORIC study comparing mogamulizumab to vorinostat, an FDA approved drug for this indication, in 372 patients. In this trial, mogamulizumab was found to have a superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat arm, with a hazard ratio of 0.53, p<0.001. Mogamulizumab was well tolerated with the most common AE being infusion-related reactions (32%), drug rash (20%), diarrhea (23%), and fatigue (22%). We reviewed the literature leading to the development and approval of mogamulizumab and suggest which patients may benefit the most from this treatment.

Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma.

Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with ≥1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase (n = 19) and 800 mg twice daily (fasting) in expansion phase (n = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively. Most frequently reported related Grade ≥3 TEAE was transaminase elevation (21%). Two dose-limiting toxicities occurred in the 800 mg fed cohort; hence, 800 mg fasting dose was deemed MTD. Tenalisib was absorbed rapidly with a median half-life of 2.28 h. Overall response rate in 35 evaluable patients was 45.7% (3 complete response (CR); 13 partial response (PR)) and median duration of response was 4.9 months. Responding tumors showed a marked downregulation of CD30, IL-31 and IL-32α. With an acceptable safety and promising clinical activity, Tenalisib can be a potential therapeutic option for relapsed/refractory TCL. Currently, a phase I/II combination study with romidepsin is ongoing.

Patient-reported quality of life in patients with relapsed/refractory cutaneous T-cell lymphoma: Results from the randomised phase III ALCANZA study.

BACKGROUND: Brentuximab vedotin was approved for adult patients with CD30-expressing cutaneous T-cell lymphoma treated with prior systemic therapy based on improved response rates and progression-free survival with brentuximab vedotin (1.8 mg/kg once every 3 weeks; ≤16 cycles) versus physician's choice (methotrexate/bexarotene; ≤48 weeks) in the phase III ALCANZA study. Quality of life (QoL) in ALCANZA patients was also examined. METHODS: QoL measures in ALCANZA were based on the Skindex-29, Functional Assessment of Cancer Therapy-General (FACT-G) and European QoL 5-dimension (EQ-5D) questionnaires. RESULTS: Mean maximum reduction from the baseline Skindex-29 symptom domain score (key secondary end-point) was greater with brentuximab vedotin than physician's choice (-27.96 versus -8.62); the difference, -18.9 (95% confidence interval -26.6, -11.2; adjusted p < 0.001), exceeded the study-defined minimally important difference (9.0-12.3). Mean changes from baseline to end-of-treatment visit total FACT-G scores were similar with brentuximab vedotin and physician's choice (0.15 versus -2.29). EQ-5D changes were also comparable between arms. Among brentuximab vedotin-treated patients with peripheral neuropathy (PN), mean maximum reduction in Skindex-29 symptom domain was -35.54 versus -11.11 in patients without PN. PN had no meaningful effect on FACT-G and EQ-5D QoL scores. CONCLUSIONS: In summary, brentuximab vedotin produced superior reductions in symptom burden compared with physician's choice, without adversely impacting QoL. QoL was unaffected by the presence of PN in brentuximab vedotin-treated patients. CLINICAL TRIAL REGISTRATION: NCT01578499.

Outcomes of Patients with Transformed Mycosis Fungoides: Analysis from a Prospective Multicenter US Cohort Study.

INTRODUCTION: We examined patient characteristics, treatments, and outcomes of patients with transformed mycosis fungoides (tMF) from COMPLETE: a large, multicenter, prospective cohort study of peripheral T-cell lymphoma patients in the United States. METHODS: Patients with tMF were enrolled in COMPLETE at the time of transformation. For this analysis, we identified patients with tMF with completed baseline, treatment, and follow-up records. Median survival was assessed using Kaplan-Meier methodology. RESULTS: Of the 499 patients enrolled in COMPLETE, 17 had tMF. Median age was 61; 53% were male, 9 had elevated lactate dehydrogenase, and 9 had lymph node involvement. Approximately one-quarter of the patients were African American and 47% had CD30+ disease. Median time to transformation was 53 months. All patients received systemic therapy, with 19% receiving concomitant radiotherapy. Most patients (87%) received single agents, including liposomal doxorubicin, pralatrexate, and gemcitabine. Eight patients (50%) had reported responses to therapy. Median survival was 18 months. One- and 2-year survival rates were 56% and 44%, respectively. CONCLUSIONS: tMF often expresses CD30 and presents with lymph node involvement. Responses have been seen with single agents, but survival remains poor. Novel treatment approaches are urgently needed to improve outcomes.

B-cell lymphomas associated with breast implants: Report of three cases and review of the literature.

Since the first reported case in 1997, over 600 women with breast implant-associated anaplastic large cell lymphoma (BI ALCL) have been reported. BI ALCL is a CD30-positive T-cell lymphoma that carries clonal T-cell receptor gene rearrangements, and a subset of cases harbors mutations in the JAK-STAT signaling pathway. Rarely, other histologic types of lymphoma have been reported in association with breast implants, including fewer than 10 cases of B-cell origin. Here, we describe three additional patients with B-cell lymphoma occurring around breast implants. Two of these patients developed extranodal marginal zone lymphoma in the peri-implant capsule, one of which had a concurrent ALCL within the superficial lining of the capsule. The third patient presented with diffuse large B-cell lymphoma inside the breast parenchyma surrounding her implant. Determining the etiology and risk factors for the development of B-cell lymphomas associated with breast implants remains challenging, given the wide spectrum of histologic features and the rarity of these neoplasms. Ultimately, we document three new cases of B-cell lymphoma arising around breast implants and highlight their clinical and pathologic features in order to expand our understanding of this rare disease presentation.