Explore the vast range of titles available.

Present first-line therapy for diffuse large B-cell lymphoma, a subtype of non-Hodgkin lymphoma, is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Ibrutinib, a novel oral Bruton's tyrosine kinase inhibitor, has shown single-drug activity in relapsed or refractory B-cell malignancies. We investigated the safety and efficacy of ibrutinib in combination with R-CHOP for patients with previously untreated CD20-positive B-cell non-Hodgkin lymphoma. In this phase 1b, open-label, non-randomised study, patients were recruited across six centres in the USA and France. Eligibility was age 18 years or older and treatment-naive histopathologically confirmed CD20-positive B-cell non-Hodgkin lymphoma. In the dose-escalation phase (part 1), patients with diffuse large B-cell lymphoma, mantle-cell lymphoma, or follicular lymphoma were enrolled. The primary objective was to determine a recommended phase 2 dose of ibrutinib with a standard R-CHOP regimen, by assessing safety in all patients who received treatment. Patients received ibrutinib 280 mg, 420 mg, or 560 mg per day in combination with a standard R-CHOP regimen every 21 days. Safety of the recommended phase 2 dose was then assessed in a dose-expansion population, which consisted of patients with newly diagnosed diffuse large B-cell lymphoma (part 2). Secondary objectives included assessments of the proportion of patients who had an overall response, pharmacokinetics, and pharmacodynamics. This trial is registered with ClinicalTrials.gov, number NCT01569750. From June 22, 2012, to March 25, 2013, 33 patients were enrolled (part 1: 17; part 2: 16) and 32 received ibrutinib plus R-CHOP treatment (one patient in the part 2 cohort withdrew). The maximum tolerated dose was not reached and the recommended phase 2 dose for ibrutinib was 560 mg per day. The most common grade 3 or greater adverse events included neutropenia (73% [24 of 33 patients]), thrombocytopenia (21% [seven patients]), and febrile neutropenia and anaemia (18% each [six patients]). The most frequently reported serious adverse events were febrile neutropenia (18% [six patients]) and hypotension (6% [two patients]). 30 (94%) of 32 patients who received one or more doses of combination treatment achieved an overall response. All 18 patients with diffuse large B-cell lymphoma who received the recommended phase 2 dose had an overall response. For those subtyped and treated at the recommended phase 2 dose, five (71%) of seven patients with the germinal centre B-cell-like subtype and two (100%) patients with the non-germinal centre B-cell-like subtype had a complete response. R-CHOP did not affect pharmacokinetics of ibrutinib, and ibrutinib did not alter the pharmacokinetics of vincristine. Pharmacodynamic data showed Bruton's tyrosine kinase was fully occupied (>90% occupancy) at the recommended phase 2 dose. Ibrutinib is well tolerated when added to R-CHOP, and could improve responses in patients with B-cell non-Hodgkin lymphoma, but our findings need confirmation in a phase 3 trial. Janssen.

Classical Hodgkin lymphoma is one of the more frequent lymphomas and is generally considered a highly curable disease with standard first-line chemotherapy and radiotherapy in some cases. Despite these outstanding results, major problems remain unresolved. First, there are still patients who will not be cured with front-line regimens and, second, many patients who are cured of classical Hodgkin lymphoma continue to die prematurely due to the late toxic effects of their therapy. Because the median age of patients with classical Hodgkin lymphoma is in the mid-30s, the disease's impact on the number of years lost from productive life is remarkable. In recent years, the gold standard of chemotherapy (often combined with radiotherapy) has changed, with the approval of immunotherapy mostly in relapse settings.

Optimal management of patients who present with Hodgkin lymphoma continues to evolve. Most patients are cured with current treatment strategies, some but both short and long‐term morbidity and mortality from treatment have particular relevance given the youth of the patient population. Combininations of targeted agents together with conventional chemotherapy have recently been investigated in phase 3 cliniial trials for advanced‐stage Hodkgkin lymphoma, and have demonstrated improved efficacy compared with chemotherapy alone. These include both antibody‐drug conjugates and PD‐1 blockade. Treatment approaches have historically differed between pediatric and adult groups, but recent collaborations between adullt and pediatric groups via the NCTN mechanism have resulted in the successful completion of enrollment in an advanced‐stage Hodgkin lymphoma and the opening of an early‐stage trial that will enroll patients accross a broad age spectrum. Novel approachs incorporating targeted and immunomodulatory agents in the relapse setting are being actively investagated in the relapse setting as well.

PET after 2 ABVD cycles (PET-2) is widely adopted to select patients with classical Hodgkin lymphoma (cHL), who might benefit from intensifying or de-escalating therapy. Prolonged progression-free survival (PFS) has been reported in PET-2 positive patients switched to escalated BEACOPP (eBEACOPP) or BEACOPP-14. Nevertheless, the subgroup of patients with a PET-2 scored 5 according to Deauville score (PET-2 DS5) are known to poorly benefit from treatment intensification. To elucidate PET-2 DS5 outcome along with possible predictive factors of response to intensification, a pooled analysis from three multicenter trials, GITIL/FIL HD0607, RATHL, and SWOG S0816, was conducted. PFS and overall survival (OS) were assessed after 41-month median follow-up, the prognostic value of clinical, laboratory, and PET parameters at diagnosis was evaluated. Among 2231 patients, 136 (6%) PET-2 DS5 patients were identified. Their 3-year PFS was 32% (95% CI, 25–42), while the 3-year OS was 82% (95% CI, 75–89). In multivariate analysis low lymphocyte (< 600/mm 3 ) counts were adversely associated with PFS, whereas age ≥ 45 years and leukocytes cells count <15 × 103/μL were barely associated with short OS. The study confirms on a suitable cohort of PET-2 DS5 patients, that this high-risk cHL subgroup has an inadequate response to treatment intensification. Nevertheless, PET-2 DS5 patients may still have good outcome after subsequent salvage treatments with > 80% survival at 3 years, thus excluding a real disease refractoriness. Few distinct parameters may have specific prediction for PFS or OS.

Trial registration: ClinicalTrials.gov number: NCT01777152

The replacement of bleomycin with the immune drug conjugate brentuximab vedotin in the first-line chemotherapy regimen for advanced Hodgkin’s lymphoma prolonged both progression-free and overall survival.

Primary large B‐cell lymphomas of immune‐privileged sites (IP‐LBCLs) comprise LBCLs arising within “immune sanctuaries,” including the central nervous system (CNS), vitreoretina, and testes. Although patients present with localized disease, the prognosis remains poor with high relapse rates, either at the originating site or within another immune‐privileged site. Generally, in the presence of an antecedent IP‐LBCL, subsequent LBCLs are expected to be clonally related. However, we present a primary CNS LBCL and later primary testicular LBCL in a middle‐aged man, diagnosed over a decade apart, which proved to be clonally unrelated by targeted ultra‐deep next‐generation sequencing of the IgH locus.

Lymphoma is one of the most common cancers in adolescents and young adults, but historically, this population has had lower clinical trial enrollment and improvements in overall survival as compared to other age populations. There are multiple challenges that are unique to this population that have affected drug development and clinical trial enrollment. Our panel of experts have identified barriers, and in this review, we discuss current methods to address these barriers as well as potential solutions moving forward.

Background Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG‐PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5‐point scale (5‐PS). Methods In CALGB 50303, patients with DLBCL received frontline R‐CHOP or DA‐EPOCH‐R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5‐PS with progression‐free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. Results Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. Conclusions These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials. In this retrospective analysis of CALGB 50303 study, Torka et al. found that associations with PFS and OS when applying local review versus central review of interim PET (iPET) were comparable? SUV = 66% at iPET was associated with PFS and OS, but visual scoring systems (VSS) were not, highlighting the limitations of VSS.