Explore the vast range of titles available.

Pre-transplantation 18F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE). In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen. All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1, 8, and 15 for two 28 day cycles. After completion of brentuximab vedotin treatment, patients received a PET scan. Patients who achieved PET-negative status (a Deauville score of 1 or 2) proceeded directly to HDT/ASCT; those with persistent abnormalities on PET received two cycles of augmented ICE (augICE; two doses of ifosfamide 5000 mg/m2 in combination with mesna 5000 mg/m2 continuous infusion over 24 h, days 1 and 2; one dose of carboplatin AUC 5, day 3; three doses of etoposide 200 mg/m2 every 12 h, day 1) before consideration for HDT/ASCT. Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE; however, all patients in the intention-to-treat population were assessed for the primary outcome, which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE. This study is registered with ClinicalTrials.gov, number NCT01508312, and is no longer accruing patients. Between Jan 5, 2012, and Oct 4, 2013, we enrolled 46 patients. One patient was deemed ineligible, and not evaluable, before treatment initiation owing to having nodular, lymphocyte-predominant Hodgkin's lymphoma and thus 45 patients received treatment. After brentuximab vedotin, 12 patients (27%, 95% CI 13–40) were PET-negative and proceeded to HDT/ASCT. 33 (73%, 95% CI 60–86) patients were PET-positive after brentuximab vedotin; one PET-positive patient withdrew consent, therefore 32 PET-positive patients received augICE, 22 (69%, 95% CI 53–85) of whom were PET-negative. Overall, 34 patients (76%, 95% CI 62–89) achieved PET-negativity. All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT. Brentuximab vedotin was well tolerated and associated with few grade 3–4 adverse events including hyperglycaemia (two [4%] patients, grade 3), nausea (one [2%], grade 3), hypoglycaemia (one [2%], grade 3 and one [2%], grade 4), and hypocalcaemia (one [2%], grade 3 and one [2%], grade 4). PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE resulted in a high proportion of patients with relapsed or refractory Hodgkin's lymphoma achieving PET-negativity, and therefore could optimise the chance of cure after HDT/ASCT. Seattle Genetics.

Patients with follicular lymphoma (FL) frequently require multiple treatments during their disease course; however, survival based on lines of treatment remains poorly described in the post-rituximab era. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score was developed to predict survival at diagnosis, yet it remains unknown whether increase in FLIPI score following an initial observation period is associated with less-favorable outcomes. To address these knowledge gaps, we retrospectively studied 1088 patients with FL grade 1–3A managed between 1998 and 2009 at our institution. Median overall survival (OS) and progression-free survival (PFS) after first-line treatment were not reached and 4.73 years, respectively. Following successive lines of treatment, years of median OS and PFS were, respectively: after second-line, 11.7 and 1.5; third-line, 8.8 and 1.1; fourth-line, 5.3 and 0.9; fifth-line, 3.1 and 0.6; sixth-line, 1.9 and 0.5. In initially observed, subsequently treated patients, FLIPI score increase after observation was associated with inferior survival following first-line treatment. The reduced survival we observed after second-line and later therapy supports the development of new treatments for relapsed patients and benchmarks historical targets for clinical endpoints. This study also highlights the utility of changes in FLIPI score at diagnosis and after observation in identifying patients likely to have worse outcomes.

Characteristics Overalla Single lesiona Multifocala N = 44 N = 31 N = 13 Median Age 75 (40, 96) 76 (40, 89) 72 (43, 96) Gender  F 21 (48%) 15 (48%) 6 (46%)  M 23 (52%) 16 (52%) 7 (54%) Race  White 33 (87%) 25 (93%) 8 (73%)  Asian 3 (8%) 1 (4%) 2 (18%)  African American 1 (3%) 1 (4%) 0 (0%)  Other 1 (3%) 0 (0%) 1 (9%)  Unknown 6 4 2 Ethnicity  Not hispanic 38 (97%) 27 (100%) 11 (92%)  Hispanic or latino 1 (3%) 0 (0%) 1 (8%)  Unknown 5 4 1 B symptoms 0 (0%) 0 (0%) 0 (0%) ECOG PS  0 28 (64%) 21 (68%) 7 (54%)  1 14 (32%) 8 (26%) 6 (46%)  2/3 2 (4.5%) 2 (6.5%) 0 (0%) Skin site  Lower extremity 18 (41%) 10 (32%) 8 (62%)  Other site 26 (59%) 21 (68%) 5 (38%) Bulky mass (>5 cm) 5 (14%) 3 (13%) 2 (15%)  Unknown 7 7 0 White blood cells * 1000/microL 7.0 (2.6, 12.6) 6.8 (4.3, 12.6) 7.4 (2.6, 10.8)  Unknown 3 2 1 Hemoglobin, g/dL 13.4 (9.9,16.1) 13.5 (11.0, 16.1) 12.9 (9.9, 15.0)  Unknown 4 3 1 Platelets * 1000/microL 218 (126, 453) 199 (126, 383) 234 (175, 453)  Unknown 3 2 1 Albumin, g/dL 4.2 (3.5, 27.0) 4.2 (3.8, 27.0) 4.2 (3.5, 4.7)  Unknown 4 3 1 Elevated LDH 8 (19%) 7 (23%) 1 (8%)  Unknown 2 1 1 IPI  0/1 32 (76%) 22 (73%) 10 (83%)  2 9 (21%) 7 (23%) 2 (17%)  3 1 (2%) 1 (3%) 0 (0%)  Unknown 2 1 1 CNS-IPI  0/1 30 (71%) 21 (70%) 9 (75%)  2/3 12 (29%) 9 (30%) 3 (25%)  Unknown 2 1 1 Additional cancers 23 (52%) 16 (52%) 7 (54%) Additional skin cancers 15 (34%) 10 (32%) 5 (38%) First-line Treatment  RT 11 (25%) 9 (29%) 2 (15%)  Chemotherapy 15 (34%) 10 (32%) 5 (38%)  Chemotherapy + RT 15 (34%) 10 (32%) 5 (38%)  Other 3 (7%) 2 (6.5%) 1 (8%) First-line CNS prophylaxis 6 (14%) 3 (10%) 3 (23%) PS performance status, LDH lactate dehydrogenase, IPI international prognostic index, CNS central nervous system, RT radiation therapy. aValues reported as n (%) or as median (range). All 44 patients were evaluable for response, with an overall response rate (ORR) of 86% and complete response (CR) rate of 84%. There was no significant difference in response rates (p = 0.13) among the RT, CHT and CMT groups. No significant differences in response rates (p = 0.4) or PFS (p = 0.8) (supplemental tables 3, 4) were observed between the two groups, while a trend toward improved OS was noted in patients with a single lesion, with a median OS of 14 years (95%CI, 9.9-NR), compared to 4.6 years (95%CI, 2.6-NR) for those with multifocal disease (p = 0.11, supplemental table 5 and supplemental Fig. 1).

Historic outcomes for patients with relapsed or refractory nodal-based T-cell lymphomas are poor, with survival generally measured in months in multiple reports from the late 20th and early 21st century. Until recently, salvage strategies have mostly been borrowed from other aggressive lymphomas. However, dedicated investigations into the pathogenesis of T-cell lymphomas have resulted in an outpouring of therapies that target these diseases in biologically rational strategies. In particular, an evolving appreciation of the multiple complex oncogenic pathways and epigenetic changes that underlie these diseases has led to numerous agents targeting these aberrancies. Moreover, large reports of salvage allogeneic stem cell transplants in T-cell lymphoma have now been published, showing that adaptive immunotherapy is a potentially curative strategy for patients with relapsed or refractory disease. This review highlights therapeutic advances for relapsed or refractory T-cell lymphomas, including cellular therapy and allogeneic stem cell transplant, and provides a framework for management.

Introduction: Immune evasion through inhibition of effector T cells is a key survival mechanism of lymphoma cells. We hypothesized that reinstating effector T cell activity through concurrent inhibition of the PD1/PD-L1 axis and of Treg activity will result in a synergistic anti-tumor effect with an acceptable toxicity profile. Methods: Phase I multi-institutional NCI-ETCTN trial aimed to evaluate the safety and tolerability of the combination of mogamulizumab and pembrolizumab in relapsed or refractory non-Hodgkin lymphoma. The study used a 3 + 3 design. Treatment consisted of mogamulizumab 1 mg/kg on days 1, 8, and 15 of cycle 1, followed by 1.5 mg/kg on day 1 of each subsequent 21-day cycle in combination with pembrolizumab 200 mg on day 1 of each cycle. A de-escalation level was defined as a 50% reduction in the dose of mogamulizumab (registered in clinicaltrials.gov NCT03309878). Results: The study was discontinued early, after treating seven patients (two angioimmunoblastic T cell lymphoma, four transformed follicular lymphoma, and one diffuse large B cell lymphoma of germinal center subtype) for concerns of futility and non-tolerability. Only two patients completed the first two cycles of treatment. Three patients presented with an early progression and three withdrew consent in the setting of general deterioration with clinically suspected progression. All six patients expired shortly after withdrawal from the study. The remaining patient experienced stress cardiomyopathy during the third cycle and was taken off the study. Discussion: In striking difference to the observation in solid malignancies, the combination of mogamulizumab with pembrolizumab was associated with low tolerability and suspected hyper-progression in patients with lymphoma.

The peripheral T-cell lymphomas (PTCLs) are a notoriously diverse family of non-Hodgkin lymphomas with generally aggressive biology. Clinical management is challenging given a largely inadequate literature base comprised of few randomized trials and heterogeneous observational reports. Herein, we provide an account of our practice in the treatment of the 3 most common nodal PTCLs: PTCL, not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma (ALCL). In the up-front setting, we employ anthracycline-based induction, with the incorporation of brentuximab vedotin for all those with ALCL and consideration in those with other CD30-expressing PTCLs based on improved progression-free and overall survival in the absence of additional toxicity in the ECHELON-2 trial. We strongly consider high-dose therapy with autologous stem cell rescue in first complete remission. In the relapsed or refractory (R/R) setting, we often look to clinical trials or choose from 4 FDA-approved single agents-belinostat, brentuximab vedotin, romidepsin, and pralatrexate-based on tumor phenotype and side-effect profiles. Our goal in the R/R setting is achievement of complete remission followed by allogeneic transplant with curative intent in appropriate candidates or long-term disease control in others. Numerous investigational agents are advancing through trials and have potential to alter standards of care in the near future.

Recent prospective clinical trial data suggest that patients with Hodgkin’s lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.

[...]we believe that our results, which are based on the visual five-point scale, are accurate and clinically meaningful, and can provide guidance for future clinical studies to improve the outcome of patients with Hodgkin's lymphoma.

Despite the success of modern therapy for Hodgkin lymphoma (HL), about 15 % of patients will fail both first-line and second-line therapy and treatment options for these patients are limited. New agents are needed to improve the outcome for relapsed or refractory HL and to improve the toxicity of current front-line regimens. Brentuximab vedotin (BV) was recently approved for HL and is likely to have a tremendous impact on the current treatment paradigm for HL. Additional agents that have demonstrated activity in HL include histone deacetylase inhibitors, such as panobinostat, entinostat, and mocetinostat, PI3-kinase/Akt/Mtor pathway inhibitors, such as everolimus, as well as lenalidomide and bendamustine. Studies evaluating these agents alone or in combination with either chemotherapy or other targeted agents are ongoing. Current challenges in HL research include identifying the most appropriate drug combinations of new and old drugs and identifying predictors of response to the new targeted agents.