A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non-ibrutinib therapy, grouped as intensive (IT) or non-intensive therapy (NIT).

A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib.

Among patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), evidence from clinical trials for the effectiveness of single-agent ibrutinib as first-line therapy is limited. This retrospective analysis compared real-world clinical outcomes among patients with CLL, with and without del(17p), treated with first-line ibrutinib monotherapy. Overall survival, time to next treatment, time to treatment discontinuation, and reasons for ibrutinib discontinuation were evaluated.

Flexible and Stretchable Bioelectronics.

Medical science technology has improved tremendously over the decades with the invention of robotic surgery, gene editing, immune therapy, etc. However, scientists are now recognizing the significance of 'biological circuits' i.e.

The DOT1L inhibitor pinometostat reduces H3K79 methylation and has modest clinical activity in adult acute leukemia.

Pinometostat (EPZ-5676) is a first-in-class small-molecule inhibitor of the histone methyltransferase disrupter of telomeric silencing 1-like (DOT1L). In this phase 1 study, pinometostat was evaluated for safety and efficacy in adult patients with advanced acute leukemias, particularly those involving mixed lineage leukemia () gene rearrangements () resulting from 11q23 translocations. Fifty-one patients were enrolled into 6 dose-escalation cohorts (n = 26) and 2 expansion cohorts (n = 25) at pinometostat doses of 54 and 90 mg/m per day by continuous intravenous infusion in 28-day cycles.

Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.

Background: Activating enhancer of zeste homolog 2 (EZH2) mutations or aberrations of the switch/sucrose non-fermentable (SWI/SNF) complex (eg, mutations or deletions of the subunits INI1 or SMARCA4) can lead to aberrant histone methylation, oncogenic transformation, and a proliferative dependency on EZH2 activity. In this first-in-human study, we aimed to investigate the safety, clinical activity, pharmacokinetics, and pharmacodynamics of tazemetostat, a first-in-class selective inhibitor of EZH2.

Methods: We did an open-label, multicentre, dose-escalation, phase 1 study using a 3 + 3 design with planned cohort expansion at the two highest doses below the maximally tolerated dose.

Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC.

Specificity protein 1 (Sp1) transcription factor (TF) regulates expression of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) cells. RNA interference (RNAi) studies showed that among several lncRNAs expressed in HepG2, SNU-449 and SK-Hep-1 cells, highly upregulated in liver cancer (HULC) was regulated not only by Sp1 but also Sp3 and Sp4 in the three cell lines. Knockdown of Sp transcription factors and HULC by RNAi showed that they play important roles in HCC cell proliferation, survival and migration.

Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia.

Background: The treatment of relapsed chronic lymphocytic leukemia (CLL) has resulted in few durable remissions. Bruton's tyrosine kinase (BTK), an essential component of B-cell-receptor signaling, mediates interactions with the tumor microenvironment and promotes the survival and proliferation of CLL cells.

Methods: We conducted a phase 1b-2 multicenter study to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ibrutinib (PCI-32765), a first-in-class, oral covalent inhibitor of BTK designed for treatment of B-cell cancers, in patients with relapsed or refractory CLL or small lymphocytic lymphoma.

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

Purpose: Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies.

Patients And Methods: Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib.

Bevacizumab beyond first progression is associated with prolonged overall survival in metastatic colorectal cancer: results from a large observational cohort study (BRiTE).

Purpose: Bevacizumab provides a survival benefit in first- and second-line metastatic colorectal cancer (mCRC). In a large, observational, bevacizumab treatment study (Bevacizumab Regimens: Investigation of Treatment Effects and Safety [BRiTE]) in patients who had mCRC, a longer-than-expected overall survival (OS) of 25.1 months was reported.

Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study.

Purpose: To evaluate the safety and efficacy of three oxaliplatin and fluoropyrimidine regimens, with or without bevacizumab, as first-line treatment for metastatic colorectal cancer (CRC).

Patients And Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease were randomly assigned to mFOLFOX6 (bolus and infusion fluorouracil [FU] and leucovorin [LV] with oxaliplatin), bFOL (bolus FU and low-dose LV with oxaliplatin), or CapeOx (capecitabine with oxaliplatin), respectively (Three Regimens of Eloxatin Evaluation [TREE-1]). The study was later modified such that subsequent patients were randomized to the same regimens plus bevacizumab (TREE-2).

Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107.

Purpose: In the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.

Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma.

Background: In the era of highly active antiretroviral therapy (HAART), standard-dose chemotherapy for human immunodeficiency virus (HIV)-associated diffuse large B-cell lymphoma is becoming the standard of care. In contrast, the safety and efficacy of intensive regimens have not been established for Burkitt lymphoma (BL), a highly aggressive lymphoma for which moderate-dose chemotherapy is substandard in the HIV-negative population.

Methods: To evaluate the feasibility of intensive chemotherapy in HIV-associated BL, the authors retrospectively reviewed 14 HIV-positive adults with BL treated at their center between 1988 and 2000.

Rituximab: ongoing and future clinical development.

Monoclonal antibodies have been used as therapeutic agents for many years. In 1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be approved by the US Food and Drug Administration for a cancer indication. The use of rituximab in the treatment of low-grade or follicular, relapsed, or refractory CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for United States marketing under the trade name Rituxan.

Rituximab: Ongoing and future clinical development.

Monoclonal antibodies have been used as therapeutic agents for many years. In 1997, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) became the first monoclonal antibody to be approved by the US Food and Drug Administration for a cancer indication. The use of rituximab in the treatment of low-grade or follicular, relapsed, or refractory CD20-positive B-cell non-Hodgkin's lymphoma was approved in November 1997 for United States marketing under the trade name Rituxan.