Venetoclax monotherapy as front-line therapy for blastic plasmacytoid dendritic cell neoplasm.

Venetoclax is an approved treatment for relapsed/refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN). We report a unique case of venetoclax monotherapy used for front-line induction and as a bridge to allogeneic hematopoietic stem cell transplantation (HCT). Venetoclax therapy resulted in rapid complete resolution of skin lesions, however, treatment interruption due to neutropenia led to brisk cancer recurrence. Fortunately, the patient responded to re-challenge and was able to undergo HCT. Venetoclax is active in the first-line treatment setting for BPDCN, however its effect on blood counts and durability of response should be further studied.

Belumosudil for chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGvHD) is a multisystem disease that is diagnosed in up to 70% of patients following allogeneic hematopoietic cell transplantation. In cGvHD, the donor immune cells attack the patient's cells, resulting in inflammation and fibrosis in multiple tissues. cGvHD can affect almost any organ and is the major cause of morbidity and mortality in transplant survivors. Rho-associated coiled-coil-containing protein kinase (ROCK) is a signaling pathway that modulates inflammatory response and fibrotic processes and is dysregulated in autoimmune disorders. Many inhibitors targeting the ROCK pathway have been studied, but most lack isoform selectivity resulting in dose-limiting effects. Belumosudil mesylate is a selective oral ROCK2 inhibitor that has demonstrated safety and efficacy for cGvHD. It has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years and older with cGvHD after failure of at least two prior lines of systemic therapy, becoming the first and only approved therapy targeting ROCK2. This review examines the preclinical and clinical studies leading to the first approval of the novel drug belumosudil for cGvHD.

The evolving role of targeted biological agents in the management of indolent B-cell lymphomas.

Improved understanding of the mechanisms of lymphomagenesis has resulted in a surge of development for new targeted agents. An impressive number of biological agents targeting different steps in the pathways of tumor proliferation, survival and apoptosis have become available. The management of patients with indolent non-Hodgkin lymphomas (iNHLs) is rapidly transforming with incorporation of those targeted biological agents into the front-line and relapsed/refractory setting. This review highlights several categories of novel biological agents and will discuss their potential role in the contemporary management of patients with iNHLs.