Novel Therapies for Glioblastoma.

Purpose Of Review: Glioblastoma (GBM) is the most common malignant primary brain tumor, and the available treatment options are limited. This article reviews the recent preclinical and clinical investigations that seek to expand the repertoire of effective medical and radiotherapy options for GBM.

Recent Findings: Recent phase III trials evaluating checkpoint inhibition did not result in significant survival benefit.

Checkpoint blockade treatment sensitises relapsed/refractory non-Hodgkin lymphoma to subsequent therapy.

Patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment.

Polatuzumab Vedotin: a New Target for B Cell Malignancies.

Purpose Of Review: Antibody-drug conjugates are a new class of therapeutic agents in the treatment of B cell malignancies. In this review, we summarize the recent developments of polatuzumab vedotin in the treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

Recent Findings: Polatuzumab vedotin recently received its first FDA approval in combination with bendamustine and rituximab for the treatment of patients with relapsed or refractory DLBCL.

Advances in Therapy for Relapsed or Refractory Hodgkin Lymphoma.

Purpose Of Review: The landscape of relapsed or refractory (R/R) Hodgkin lymphoma (HL) treatment has changed significantly since the FDA approval of brentuximab vedotin in 2011. In this review, we summarize the recent advances in the therapy for R/R classical Hodgkin lymphoma (cHL).

Recent Findings: Immunotherapies with pembrolizumab, nivolumab, and ipilimumab, and chimeric antigen receptor (CAR) T cell therapies have shown promising results in early phase trials.

Are Biosimilars the Future of Oncology and Haematology?

Biological drugs are vital but often high-cost components of cancer treatment. Several biosimilar versions of these drugs have been approved in Europe and/or the USA, with many more in development. However, there is some disconnect between the biosimilars that are approved for use and those accessible in clinical practice, with availability impacted by factors including patent litigation and complex healthcare insurance policies, particularly in the USA.

Clinical development of CT-P6 in HER2 positive breast cancer.

: CT-P6 (trastuzumab-pkrb, Herzuma) is a trastuzumab biosimilar approved for use in HER2 positive breast cancer and HER2 positive gastric cancer. CT-P6 has been shown to exhibit similar safety and efficacy profiles to its reference product, trastuzumab. Preclinical and clinical studies have been performed to prove equivalence between CT-P6 and the trastuzumab originator.

An evaluation of brentuximab vedotin as a treatment option for stage III/IV Hodgkin lymphoma.

: Outcomes of patients with classical Hodgkin lymphoma are excellent, and the intent of frontline therapy for even advanced-stage disease has been curative. This review summarizes the role of brentuximab vedotin in the upfront treatment of advanced stage classical Hodgkin lymphoma in the context of reducing therapy-related toxicity without compromising the high cure rate. : Strategies to reduce bleomycin-induced lung toxicity include a response-adapted approach investigated in the RATHL study and a replacement of bleomycin with brentuximab vedotin in frontline chemotherapy regimens.

Molecular and metabolic pathways mediating curative treatment of a non-Hodgkin B cell lymphoma by Sindbis viral vectors and anti-4-1BB monoclonal antibody.

Background: Limitations to current therapies for treating non-Hodgkin B cell lymphoma include relapse, toxicity and high cost. Thus, there remains a need for novel therapies. Oncolytic viral (OV) therapy has become a promising cancer immunotherapy because of its potential effectiveness, specificity and long-lasting immunity.

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study.

Background: In the Mammary Oncology Assessment of LEE011's (Ribociclib's) Efficacy and Safety (MONALEESA-2) study, combination treatment with the selective inhibitor of cyclin-dependent kinases 4/6 ribociclib with letrozole significantly improved progression-free survival (PFS) versus letrozole alone in postmenopausal women with hormone receptor-positive HR/HER2 advanced breast cancer (ABC). Herein we present results from the subset of US patients enrolled in MONALEESA-2.

Patients And Methods: Postmenopausal women with HR/HER2 ABC without previous treatment for advanced disease were randomized (1:1) to ribociclib 600 mg/d (3 weeks on/1 week off) with letrozole 2.

Immune targeting of the microenvironment in classical Hodgkin's lymphoma: insights for the hematologist.

While up to 80% of patients with Hodgkin's lymphoma (HL) are cured with first-line therapy, relapsed/refractory (R/R) disease remains a clinical challenge and is fatal for many young patients. HL is unique in that the tumor cells (Hodgkin Reed-Sternberg; HRS cells) are a small fraction (<1%) of the tumor bulk, with the remaining tumor composed of the cells of the tumor microenvironment (TME). The support and integrity of the TME is necessary for HRS cell growth and survival.

New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little?

Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits.

Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization.

Purpose: Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen.

Patients And Methods: COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase.

An Overlapping Region between the Two Terminal Folding Units of the Outer Surface Protein A (OspA) Controls Its Folding Behavior.

Although many naturally occurring proteins consist of multiple domains, most studies on protein folding to date deal with single-domain proteins or isolated domains of multi-domain proteins. Studies of multi-domain protein folding are required for further advancing our understanding of protein folding mechanisms. Borrelia outer surface protein A (OspA) is a β-rich two-domain protein, in which two globular domains are connected by a rigid and stable single-layer β-sheet.

Efficacy and safety of the trastuzumab biosimilar candidate CT-P6.

Trastuzumab is an anti-HER2 monoclonal antibody indicated for the treatment of HER2-overexpressing breast and gastric cancers. Despite its clinical efficacy, access to the biological drug can be limited due to its relatively high price, especially in low-income countries. CT-P6 (Herzuma) is a biosimilar candidate of originator or 'reference' trastuzumab, which may offer an alternative, more cost-effective treatment option.