ABSTRACT
High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improved 5-year overall survival rates in relapsed/refractory germ cell tumors (GCTs) from 10% to 52%. Nearly 30% of GCT patients are deemed poor mobilizers after receiving several lines of prior therapy. There is limited data available regarding upfront plerixafor use in GCT patients. We predicted upfront plerixafor use would increase the amount of stem cells collected preventing subsequent mobilizations and improve time to curative therapy. A retrospective, single center, chart review of adult GCT patients who received plerixafor upfront for mobilization at a single center between January 1, 2013 and August 31, 2021 was performed. The primary objective was to evaluate the rate of successful peripheral blood CD34+ cell collections. Secondary objectives consisted of describing the impact of plerixafor use on mobilization and assessing auto-HSCT related outcomes. Sixteen patients received plerixafor upfront after an average of three prior lines of therapy (range: 2-5 lines). Successful collection (≥4 × 106 CD34+ cells/Kg collected within four days) was achieved in 15 (94%) patients in a median of one apheresis day (interquartile range: 1-2 days). All patients proceeded to an initial auto-HSCT and 12 patients (75%) completed both transplants as planned. Survival at 12 months was 50%. The significantly higher amount of CD34+ cells collected over less apheresis days demonstrated the clinical utility of upfront plerixafor and its potential to facilitate more efficient stem cell mobilization. There is a need for larger randomized studies with upfront plerixafor use in this unique patient population.
ABSTRACT
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.
