BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis.

Introduction: The prognostic value of B-cell lymphoma 2 (BCL2) expression in de novo diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy is of interest to define a target patient population for clinical development of BCL2 inhibitors. We aimed to develop a reproducible immunohistochemistry algorithm and assay to determine BCL2 protein expression and assess the prognostic value of BCL2 in newly diagnosed DLBCL cohorts.

Patients And Methods: The prospectively defined algorithm incorporated BCL2 staining intensity and percentage of BCL2-positive cells.

Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study.

Purpose: The Chinese bridging study PUFFIN (NCT02896855) aimed to assess consistency of efficacy with CLEOPATRA (NCT00567190), investigating pertuzumab with trastuzumab and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer.

Methods: Patients were randomized 1:1, stratified by visceral/non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS).

Safety and efficacy of obinutuzumab with CHOP or bendamustine in previously untreated follicular lymphoma.

The GAUDI study assessed safety and preliminary efficacy of induction therapy with obinutuzumab plus chemotherapy, followed by maintenance therapy with obinutuzumab alone, in previously untreated patients with follicular lymphoma. Assignment to chemotherapy was decided on a per-center basis before the patients' enrollment. Patients (n=81) received four to six cycles of obinutuzumab plus bendamustine every 4 weeks or six to eight cycles of obinutuzumab plus CHOP every 3 weeks.

Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study.

GAUGUIN evaluated the safety and efficacy of obinutuzumab (GA101) monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In phase 1 (dose escalation), 13 patients received obinutuzumab 400 to 1200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2-8). In phase 2, 20 patients received a fixed dose of 1000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2-8).

IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis.

Objectives: To determine whether heterogeneity in interleukin-6 (IL-6), IL-6 receptor and other components of the IL-6 signalling pathway/network, at the gene, transcript and protein levels, correlate with disease activity in patients with rheumatoid arthritis (RA) and with clinical response to tocilizumab.

Design: Biomarker samples and clinical data for five phase 3 trials of tocilizumab were analysed using serum (3751 samples), genotype (927 samples) and transcript (217 samples) analyses. Linear regression was then used to assess the association between these markers and either baseline disease activity or treatment response.

Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000).

The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses.

Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large b-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study.

Purpose: Obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL.

Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study.

Purpose: The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma.

Patients And Methods: Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg).

Results: Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory.

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis.

Background: Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients.

Objective: To carry out a meta-analysis of trials from the rituximab RA clinical programme to investigate this relationship further.

Methods: This was a meta-analysis of four placebo-controlled, phase II or III clinical trials.

Analysing time course microarray data using Bioconductor: a case study using yeast2 Affymetrix arrays.

Background: Large scale microarray experiments are becoming increasingly routine, particularly those which track a number of different cell lines through time. This time-course information provides valuable insight into the dynamic mechanisms underlying the biological processes being observed. However, proper statistical analysis of time-course data requires the use of more sophisticated tools and complex statistical models.

A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection.

Background: Telomeres prevent the ends of eukaryotic chromosomes from being recognized as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harboring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were subjected to a transcriptomic study.