Radiation and Dose-densification of R-CHOP in Aggressive B-cell Lymphoma With Intermediate Prognosis: The UNFOLDER Study.

UNFOLDER (Unfavorable Young Low-Risk Densification of R-Chemo Regimens) is an international phase-3 trial in patients 18-60 years with aggressive B-cell lymphoma and intermediate prognosis defined by age-adjusted International Prognostic Index (aaIPI) of 0 and bulky disease (≥7.5 cm) or aaIPI of 1. In a 2 × 2 factorial design patients were randomized to 6× R-CHOP-14 or 6× R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso[lo]ne) and to consolidation radiotherapy to extralymphatic and bulky disease or observation.

Radiation and Dose-densification of R-CHOP in Primary Mediastinal B-cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial.

UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans.

First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial.

The incidence of aggressive B-cell lymphomas increases with age, but for elderly or frail patients not eligible for doxorubicin-containing treatment standard therapy remains to be defined. In this prospective, multicenter, phase-2 B-R-ENDA trial, we investigated the feasibility, toxicity, and efficacy of 8 cycles rituximab combined with 6 cycles bendamustine (BR) in elderly or frail aggressive B-cell lymphoma patients: 39 patients aged >80 years and 29 patients aged 61-80 years with elevated Cumulative Illness Rating Scalescore >6 were included. Progression-free survival (PFS) and overall survival (OS) at 2 years were 45% (95% confidence interval [CI], 28%-61%) and 46% (28%-63%) for the patients age >80, as well 32% (13%-51%) and 37% (17%-57%) for frail patients age 64-80, respectively.

A phase II trial to evaluate the combination of pixantrone and obinutuzumab for patients with relapsed aggressive lymphoma: Final results of the prospective, multicentre GOAL trial.

The prognosis of patients with relapsed diffuse large B-cell lymphoma (DLBCL) remains poor with current options. Here we prospectively evaluated the combination of pixantrone with obinutuzumab for up to six cycles for patients with relapsed or refractory DLBCL. Overall response rate (ORR) was the primary end-point.

Significant reduced loss of bone mineral density after four vs. six cycles of R-CHOP: an analysis of the FLYER-trial.

Patients with diffuse large B-cell lymphoma (DLBCL) treated with the R-CHOP regime receive a high cumulative dose of prednisone. We used computer tomography-ascertained Hounsfield units (HU) as a surrogate parameter for bone mineral density (BMD) in three different locations of the L3 vertebral body at baseline and post-treatment. HU were measured in 50 patients with DLBCL of the previously published FLYER-trial which compared four cycles of R-CHOP + 2 × rituximab infusion to six cycles of R-CHOP in young, favorable DLBCL patients.

CAMK1D Triggers Immune Resistance of Human Tumor Cells Refractory to Anti-PD-L1 Treatment.

The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen to identify genes that mediated resistance against CTLs in anti-PD-L1 treatment-refractory human tumors. Using PD-L1-positive multiple myeloma cells cocultured with tumor-reactive bone marrow-infiltrating CTL as a model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key modulator of tumor-intrinsic immune resistance.

Final Results of a Phase I/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Follicular Lymphoma.

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m, day 1 + 2) and Rituximab (375 mg/m, day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment.

Deep Learning for the Classification of Small-Cell and Non-Small-Cell Lung Cancer.

Reliable entity subtyping is paramount for therapy stratification in lung cancer. Morphological evaluation remains the basis for entity subtyping and directs the application of additional methods such as immunohistochemistry (IHC). The decision of whether to perform IHC for subtyping is subjective, and access to IHC is not available worldwide.

Health-related quality of life in the phase III GALLIUM study of obinutuzumab- or rituximab-based chemotherapy in patients with previously untreated advanced follicular lymphoma.

Health-related quality of life was a secondary endpoint in the phase III GALLIUM study in previously untreated patients with follicular lymphoma who were treated with rituximab- or obinutuzumab-chemotherapy. Patients were randomized 1:1 to receive induction therapy with obinutuzumab- or rituximab-chemotherapy and maintenance in responders. Health-related quality of life was assessed using the Functional Assessment of Cancer Treatment-Lymphoma questionnaire, incorporating well-being and lymphoma-specific subscales.

Identification of Familial Hodgkin Lymphoma Predisposing Genes Using Whole Genome Sequencing.

Hodgkin lymphoma (HL) is a lymphoproliferative malignancy of B-cell origin that accounts for 10% of all lymphomas. Despite evidence suggesting strong familial clustering of HL, there is no clear understanding of the contribution of genes predisposing to HL. In this study, whole genome sequencing (WGS) was performed on 7 affected and 9 unaffected family members from three HL-prone families and variants were prioritized using our Familial Cancer Variant Prioritization Pipeline (FCVPPv2).

Phase I dose escalation study of BI 836826 (CD37 antibody) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a tetraspanin transmembrane protein predominantly expressed on normal and malignant B cells. This phase I, open-label study used a modified 3 + 3 design to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary activity of BI 836826 in patients with relapsed/refractory B cell non-Hodgkin lymphoma (NHL; NCT01403948). Eligible patients received up to three courses comprising an intravenous infusion (starting dose: 1 mg) once weekly for 4 weeks followed by an observation period of 27 (Course 1, 2) or 55 days (Course 3).

Serological hepatitis B virus (HBV) activity in patients with HBV infection and B-cell non-Hodgkin's lymphoma.

Background: Previous epidemiological studies suggest an association between hepatitis B virus (HBV) infection and B-cell non-Hodgkin lymphoma (B-NHL). The aim of our study was to evaluate clinical characteristics and serological indicators of HBV activity in patients who were diagnosed with both HBV infection and indolent or aggressive B-NHL.

Methods: Seventy-two patients with current or resolved HBV infection and B-NHL were identified between 2000 and 2017 at our institution.

Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial.

Background: Six cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) are the standard treatment for aggressive B-cell non-Hodgkin lymphoma. In the FLYER trial, we assessed whether four cycles of CHOP plus six applications of rituximab are non-inferior to six cycles of R-CHOP in a population of patients with B-cell non-Hodgkin lymphoma with favourable prognosis.

Methods: This two-arm, open-label, international, multicentre, prospective, randomised phase 3 non-inferiority trial was done at 138 clinical sites in Denmark, Israel, Italy, Norway, and Germany.

Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study.

The MabThera and Involved field Radiotherapy study investigated efficacy and safety of involved field (IF) radiotherapy in combination with the anti-CD20 antibody Rituximab for early-stage follicular lymphoma (FL) in a prospective, single-arm multicenter phase 2 design. Eighty-five stage I-II FL patients received 8 cycles of Rituximab (375 mg/m) and IF irradiation (30/40 Gy). The primary endpoint was progression-free survival (PFS) 2 years from treatment start.

Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial.

Background: Large field irradiation had been standard for early-stage follicular lymphoma (FL) for a long time. Although involved field radiotherapy (IF-RT) was recently favored because of the toxicity of large field irradiation, smaller irradiation fields have been accompanied with an increased risk of out-of-field recurrence. The MIR (MabThera and Involved field Radiation) trial has shown that the combination of IF-RT at a dose of 30-40 Gy with the anti-CD20 antibody rituximab has led to similar efficacy compared with large field irradiation but with markedly reduced side effects.

Patients With Malignant Lymphoma and HIV Infection Experiencing Remission After First-Line Treatment Have an Excellent Prognosis.

Background: Malignant lymphoma is still the leading cause of death among AIDS-related diseases.

Patients And Methods: We performed a retrospective analysis of 50 HIV-positive lymphoma patients. The median interval between HIV and malignant lymphoma diagnosis was 4 years.

Role of virological serum markers in patients with both hepatitis B virus infection and diffuse large B-cell lymphoma.

Background: Causality between hepatitis B virus (HBV) infection and diffuse large B-cell lymphoma (DLBCL) was reported in various studies. However, the implication of different virological serum markers of HBV infection in patients with both HBV infection and DLBCL is not fully understood. The aim of this study was to investigate the impact of HBV markers on overall survival (OS) and progression-free survival (PFS) in patients with both HBV infection and DLBCL.

NKT cells - New players in CAR cell immunotherapy?

Low levels of peripheral blood natural killer T (NKT) cells in cancer patients and a favorable outcome associated with a high number of tumor-infiltrating NKT cells demonstrated in several studies indicated the important role of these immune cells in the antitumor response. With effective antitumor immunity via direct tumor lysis, cytokine modulation of effector cells and regulation of immunosuppressive cells, type I NKT cells display interesting features/properties for the rapidly developing chimeric antigen receptor (CAR) technology. Due to their restriction to the monomorphic HLA-like molecule CD1d, but not to the polymorphic human leukocyte antigen (HLA), NKT CAR cells show potential for enabling autologous and allogeneic/off-the-shelf cancer immunotherapy.

Acalabrutinib, A Second-Generation Bruton's Tyrosine Kinase Inhibitor.

The Bruton's tyrosine kinase (BTK) is an essential in the B-cell receptor (BCR) signaling pathway which was identified as crucial in the pathogenesis of B-cell malignancies. Ibrutinib, a first-in-class BTK inhibitor, has been approved for the treatment of distinct B-cell malignancies. To overcome off-target side effects of and emerging resistances to ibrutinib, more selective second-generation BTK inhibitors were developed.

Ibrutinib.

Abnormal B-cell receptor (BCR) signalling is a key mechanism of disease progression in B-cell malignancy. Bruton's tyrosine kinase (BTK) has a pivotal role in BCR signalling. Ibrutinib (PCI-32765) is a small molecule which serves as a covalent irreversible inhibitor of BTK.

Maintenance Treatment for Patients With Mantle Cell Lymphoma: A Systematic Review and Meta-analysis of Randomized Trials.

Current treatment of patient with mantle cell lymphoma (MCL) is insufficient and does not result in cure. To assess the efficacy and safety of maintenance therapy for patients with MCL, we performed a systematic review and meta-analysis of randomized controlled trials. Six trials randomizing 858 patients were included in the meta-analysis.

Selective contrast-enhanced computed tomography is appropriate in diffuse large B-cell lymphoma therapy response assessment.

Objective: Although not the gold standard, contrast-enhanced CT of neck, thorax, and abdomen/pelvis is routinely performed in diagnosis and response assessment of DLBCL. PD during first-line treatment is a relatively rare event. The question arises if the imaging of initially involved regions only might be sufficient for response evaluation.