Novel and emerging therapies for B cell lymphoma

Abstract

Lymphomas are a heterogeneous group of lymphoproliferative disorders, with unique clinical and biological characteristics that exhibit variable response to therapy. Advances in chemo-immunotherapy have improved outcomes in a number of lymphoma subtypes; however, the prognosis for many patients with relapsed and refractory disease remains poor. Novel therapies including several small molecule inhibitors and chimeric antigen receptor T cells have been approved for the treatment of different lymphoma subtypes at relapse, changing the therapy landscape and further improving survival in many of these diseases. This has led to a focus on the development of new cellular therapy, antibody-based therapy, and small molecule inhibitors for relapsed and refractory disease that offer an alternative approach to cytotoxic chemotherapy. We will review these promising novel therapies and discuss their safety and efficacy in first in human studies.

Factors Associated with Costs in Chimeric Antigen Receptor T-Cell Therapy for Patients with Relapsed/Refractory B-Cell Malignancies

“…Terwilliger found that age is a factor affecting poor prognosis 24 , as the elderly tend to have disease with more comorbidities, which increase the costs. In our study, we found that age was not correlated with increased total costs, and high CR rates of B-cell malignancies have been reported in our center and other independent clinical trials 3 – 13 . Thus, our study showed that CAR-T treatment may be a better choice for R/R B-cell malignancies compared to salvage chemotherapy and salvage allo-HSCT.…”

“…Recently, chimeric antigen receptor T cells (CAR-Ts) have been successfully employed to improve treatment outcomes for B-cell malignancies; CR rates of 70%–95% and 50%–70% for CAR-T treatment of R/R ALL 2 – 8 and B-cell lymphoma 9 – 13 have been reported in independent clinical trials, respectively. Because of the breakthrough efficacy of CAR-T therapy, on August 30, 2017, the FDA approved tisagenlecleucel (Kymriah ® , Novartis, Basel, Switzerland) in the United States for treating patients up to 25 years old with R/R ALL 14 .…”

Sirt6 promotes tumorigenesis and drug resistance of diffuse large B-cell lymphoma by mediating PI3K/Akt signaling

“…DLBCL is an extremely malignant disease characterized by dysregulation of cell proliferation and cells resistant to apoptosis [ 5 ]. Although 50–70% of DLBCL patients are responsive to standard rituximab based chemotherapy [ 6 – 8 ], the remaining relapsed or refractory patients usually die from disease progression [ 9 – 12 ]. Therefore, there is an urgent need to identify novel targeted treatment regimens for DLBCL patients.…”

New Insights into Diffuse Large B-Cell Lymphoma Pathobiology

“…Moreover, DHITsig identified a group of DLBCL with peculiar clinical features. The variable molecular signatures, which identify HGBL and are constituted by the karyotype, the immunohistochemistry, and the DHIT signature [ 30 ], uncovered novel clinical scenarios to be driven by a still evolving genomic landscape in DLBCL, and they enable a rational patient management, based on consolidated [ 26 , 33 ] and novel therapeutic approaches [ 25 , 34 ].…”