Primary Mediastinal Large B-cell Lymphoma Treatment and Prevention of Anthracycline Cardiotoxicity: A Case Report

Primary mediastinal B-cell lymphoma (PMBCL) is a relatively rare lymphoma subtype affecting mainly young adults. Its molecular signature and clinical features resemble classical Hodgkin lymphoma. The optimal chemotherapy for this lymphoma subtype has not been established. The addition of rituximab to anthracycline based chemotherapy improved response rates and survival. Many centers use R-CHOP as standard treatment, but the role of the intensified regimens and consolidation radiotherapy has to be clarified. Recent data coming from retrospective analyses and an ongoing prospective study addressing the problem of consolidation radiotherapy will help to better identify risk groups and apply risk-adapted and effective treatment strategies. The latest research has helped to understand molecular mechanisms of PMBCL pathogenesis and indicated targets of directed therapy for the future.

Flow Cytometry in the Diagnosis of Canine B-Cell Lymphoma

B cell lymphoma (BCL) is a heterogeneous group of lymphoid malignancies which comprise the majority of canine lymphomas. Diffuse large B cell lymphoma is the most common lymphoma subtype in dogs but other subtypes (e.g., marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, and others) have been described. This review aims to explore the use of flow cytometry to refine the diagnosis of canine BCL. Particular emphasis will be given to the possible identification of peculiar immunotypes, putative prognostic markers, staging and minimal residual disease.

Beyond Mortality: Health-Related Quality of Life in Adolescent and Young Adult Patients with Lymphoma: A Longitudinal Study

Introduction: Lymphoma is the most common cancer among adolescents and young adults (AYAs). We examined changes in health-related quality of life (HRQoL) and its predictors in AYA patients (pts). Patients and Methods: We identified AYA pts (aged 18-39) enrolled 2002-2015 in a prospective cohort of pts with newly diagnosed lymphoma from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource, part of the Lymphoma Epidemiology of Outcomes cohort. Enrollment could occur prior to or after initiation of treatment. We measured HRQoL using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline, 12, and 24 months. FACT-G yields five HRQoL domain scores: emotional well-being (EWB), functional WB (FWB), physical WB (PWB), social/family WB (SFWB), and total FACT-G score (a sum of the domains). Pts completing <80% of the FACT-G questions were excluded. Linear mixed models with random subject intercepts estimated changes in FACT-G scores from baseline. The covariates in multivariate analysis were lymphoma subtype, stage, and treatment. Interaction effects between treatment (chemotherapy and/or radiation) and subtype were added to the model. We calculated effect sizes (ES) for the magnitude of mean change scores: 0.2, 0.5, and 0.8 were considered small, medium, and large ESs, respectively. Only ESs for mean score differences with p<0.05 are reported. Results: We identified 467 pts; median age at diagnosis was 30 years, median follow up was 5.9 years. 53% of pts completed the baseline FACT-G assessment pre-treatment, 47% completed after treatment began. Pts assessed after treatment initiation had lower baseline total FACT-G (ES -0.25), FWB (ES -0.27), and PWB scores (-0.46); but baseline EWB was higher in pts assessed prior to treatment (ES 0.20). There was no association between HRQoL scores at baseline or over time and lymphoma subtype, stage, or treatment type, or interactions. Total FACT-G scores modestly improved over time, ES 0.32 at 1 year and ES 0.45 at 2 years after enrollment. EWB, FWB, and PWB also improved over time (ES 0.36, 0.44, 0.30 at 1 year; and 0.49, 0.56, 0.38 at 2 years, respectively). SFWB scores slightly worsened over time (ES -0.24 at 1 year and -0.12 at 2 years). Conclusions: AYA pts with lymphoma had higher baseline total FACT-G scores, FWB and PWB prior to therapy initiation compared to after initiation. HRQoL improved from diagnosis through the first 2 years after diagnosis, except for SFWB. Neither stage, lymphoma subtype, nor treatment type affected change in HRQoL. The lack of improvement in SFWB suggests social interventions and future studies should examine factors impacting SFWB in AYA pts. Disclosures Cohen: Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Flowers:Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; National Cancer Institute: Research Funding; AbbVie: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; Kite: Research Funding; V Foundation: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy; Bayer: Consultancy. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding.

Lymphoma risks in patients with rheumatoid arthritis treated with biological drugs—a Swedish cohort study of risks by time, drug and lymphoma subtype

Objectives To estimate the association between biological DMARDs (bDMARDs; overall and by drug) as used in RA and the risk of malignant lymphomas including subtypes. Methods By linking nationwide Swedish registers we identified cohorts of patients with RA initiating treatment with a bDMARD (n = 16 392), bDMARD-naïve (n = 55 253), an age- and sex-matched general population comparator cohort (n = 229 047), and all incident lymphomas 2001–16. We used Cox regression to calculate hazard ratios (HRs) of lymphoma taking calendar period and other factors into account. Results There were 82 lymphomas among the bDMARD-treated patients with RA, crude incidence rate 76/100 000 person-years, and 310 lymphomas among the bDMARD-naïve patients with RA, crude incidence rate 90/100 000 person-years. This resulted in an adjusted HR (aHR) associated with bDMARD treatment (vs not) of 1.08 (95% CI: 0.83, 1.41). The corresponding aHR for bDMARD-treated and bDMARD-naïve vs the general population was 1.65 (95% CI: 1.31, 2.08) and 1.56 (95% CI: 1.37, 1.78) respectively. Restricting follow-up period to after 2006, the aHR of lymphoma for patients with RA starting a first bDMARD vs bDMARD-naïve was 0.69 (95% CI: 0.47, 1.00), and for bDMARD treated vs patients with RA switching from one conventional synthetic DMARDs to another, aHR was 0.46 (95% CI: 0.28, 0.73). There were no signals of different risks with any particular TNF inhibitor (TNFi) agent. We found no different lymphoma subtype pattern following bDMARD therapy. Conclusion Treatment with bDMARDs, including both TNFi and non-TNFi bDMARDs, does not further increase the lymphoma risk in RA; instead, bDMARD treatment may actually reduce the excess lymphoma risk in RA.

Systematic review on the value of end-of-treatment FDG-PET in improving overall survival of lymphoma patients

This study aimed to systematically review the value of end-of-treatment 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in improving overall survival (OS) of lymphoma patients. Medline was systematically searched for (1) randomized trials comparing the OS of patients who underwent end-of-treatment FDG-PET to those without and FDG-PET-based end-of-treatment evaluation and for (2) non-randomized studies comparing the OS of patients who underwent end-of-treatment FDG-PET to a (historical) cohort of patients without an FDG-PET-based end-of-treatment evaluation. The Medline search revealed 6284 articles. However, none of these reported data on the value of end-of-treatment FDG-PET in improving OS of lymphoma patients. In conclusion, the present systematic review reveals that there is currently no study at all that evaluates the value of end-of-treatment FDG-PET in improving OS of lymphoma patients. As a result, it remains unknown whether end-of-treatment FDG-PET increases OS and in which lymphoma subtype these examinations are of particular value. Future studies are required to demonstrate its value in this setting before it can be recommended as an evidence-based diagnostic tool by guidelines on the use of imaging in lymphoma.

Lymphoma-Specific Venous Thromboembolism Score (LyV-Score): Use of Lymphoma Subtype to Refine Risk Prediction

Background: Patients (pts) diagnosed with non-Hodgkin lymphoma (NHL) have increased risk of venous thromboembolic event (VTE). Retrospective studies have observed the risk of VTE is not the same across lymphoma subtypes, with aggressive subtypes having higher risk than indolent lymphomas. Current VTE prediction models such as the Khorana score (K-Score) consider all lymphomas as having equal risk of VTE. We conducted retrospective time - based analyses to develop a VTE prediction model that includes lymphoma subtype as a risk factor. Methods: We accessed the Hematologic Malignancies Database at University Hospitals Seidman Cancer Center and collected records of pts diagnosed with diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) between 2000 and 2016. Pts with CNS involvement or active anticoagulation were excluded. FL grade 3B pts were included in the DLBCL cohort. Information retrieved included demographic characteristics, baseline disease and laboratory parameters, as well as comorbidities and diagnosis of VTE, including radiographic confirmation. Time to VTE was measured from the date of NHL diagnosis to the date of VTE incidence or censored at the date of last follow-up for those without VTE. Cumulative incidence of VTE was estimated using Kaplan-Meier method and its difference among groups was examined by log-rank test. Cumulative incidence of VTE was also calculated considering death as competing risk and comparisons done using the Gray test. Cox proportional hazards model was used to evaluate the effect of continuous and categorical covariates on cumulative incidence of VTE and to identify prognostic factors of VTE. Fifty percent of the study participants were randomly assigned to training cohort or reserved as an independent validation cohort. Performance of multivariate models was evaluated using the Akaike Information Criterion (AIC) and Concordance Index (C-Index). The final models built using the training dataset were further validated using the validation cohort. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Results: We identified 627 pts with DLBCL (n=421) or FL (n=206) with available baseline characteristics, (Table 1). After a median follow up of 48 months (range 1-191), 77 pts experienced a VTE after NHL diagnosis. The cumulative incidence of VTE at 4 years for the whole cohort was 10.5% (95% CI 8.3-13.2). DLBCL pts had a significantly higher 4 - year cumulative incidence of VTE: 13.7% (95% CI 10.8-17.5) vs. 4.0% (95% CI 2.0 - 7.9) in FL pts (p <0.0001)(Figure 1). Univariate analysis on the training cohort showed that lymphoma subtype (DLBCL vs. FL) was associated with incidence of VTE (p = 0.02); other baseline variables associated with VTE include ECOG performance status, bulky disease, history of VTE, and serum albumin, calcium, WBC count and WBC subtypes (Table 2). Analysis of overall performance of multivariate models, including the K-Score as well as the variables identified in univariate analysis, demonstrated that the addition of lymphoma subtype and albumin to the K-Score improved the C-Index and the AIC (Table 3). The Lymphoma-specific VTE Score (LyV-Score) including lymphoma subtype, presence of bulky disease, baseline WBC and serum albumin resulted in improved performance, with C-Index of 0.775 and AIC of 234.913. To further evaluate the performance of the LyV-Score model, we performed time - dependent ROC and calibration analyses. When applied to the training cohort, 2 and 4-year AUC for the LyV-Score were 0.7767 and 0.7463, respectively, whereas for the K-Score 2 and 4-year AUC were 0.6215 and 0.6032 (Figure 2). Time - based ROC analyses in the validation cohort confirmed the higher AUC achieved by the LyV-Score. Cumulative incidence analyses show the LyV-Score and the K-Score identified groups with statistically significant differences in VTE risk (Figure 3), these differences were more marked between groups identified by the LyV-Score. Conclusions: VTE risk models have considered all lymphoma subtypes as risk factor for VTE. We show this risk is not equivalent for all lymphoma subjects, with aggressive lymphoma patients presenting higher VTE risk. We have developed the LyV-Score as a VTE prediction model that incorporates NHL histologic subtype. This model shows improved performance over historic VTE risk models and can help identify lymphoma patients that may benefit from interventions to prevent VTE. Disclosures Malek: Celgene: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Medpacto: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau; Adaptive: Consultancy. Metheny:Takeda: Speakers Bureau; Incyte: Speakers Bureau. Caimi:Genentech: Research Funding; ADC Therapeutics: Research Funding; Celgene: Speakers Bureau.

Canine lymphoma: Pathological and clinical characteristics of patients treated at a referral hospital

Non-Hodgkin’s lymphomas are common canine cancers with variable demographic and clinical presentations. Their pathological characterization and treatment lag far behind those of humans. We describe consecutive lymphoma patients detected over a one-year period at the National Autonomous University of Mexico (UNAM). Of 4,512 dogs: 220 (4.9%) had a cancer diagnosis, of which 27 (0.6%) had lymphoma (12% of cancer patients). We found an association with Miniature Schnauzers, which represented 18.5% (5/27) of lymphoma patients, but it was only 6.4% (288/4,512) of the dogs studied in this time period (p < 0.011). Miniature Schnauzers and mongrels together constituted nearly half of lymphoma cases. Mean age at diagnosis was 7.5 years (3-14), with a female to male ratio of 1.7:1. We found no correlation between lymphoma and castration status. Most patients presented nodal involvement (80%), were in advanced stages III/IV (90%) and had B-cell versus T-cell tumors (64%/36%). Only two histopathological patterns were seen, both with diffuse nodal-replacement by large immunoblast and/or centroblast-like cells; one having numerous tingible-body macrophages which are suggestive of a high proliferative rate. Chemotherapy was given to 15 patients (65%) with an overall response of 73% (3 complete responses/8 partial responses) and a mean overall survival of 219 days (4-586; SD±185). One cutaneous lymphoma-patient achieved partial response (PR) with lomustine/prednisone, and treatment was still ongoing at 548 days. Earlier diagnosis, better lymphoma subtype distinction, and specific curative treatments are needed.