The Role of the Research Advanced Practice Provider in CAR T-Cell Clinical Trials.

In recent years, chimeric antigen receptor (CAR) T-cell therapy has emerged as an effective and potentially paradigm-shifting therapy for patients with refractory lymphoma and myeloma. This novel therapy involves engineering T cells to recognize specific antigens on the surface of cancer cells. Several CAR T-cell products are approved by the US Food and Drug Administration as a result of numerous clinical trials. Due to the complexity of these studies and the high level of care required for CAR T-cell therapy patients, the role of the research advanced practice provider (APP) has become increasingly central to the success of CAR T-cell trials. This review article explores the vital role of the research APP in CAR T-cell clinical trials.

Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma.

PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%), and pancreatitis (3%). Low-grade immune-related AEs were reported in 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune-related AEs occurred in 13% of the patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. The overall response rate (primary end point) was 67%, and the complete response (CR) rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% confidence interval, 8.2-27.6), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow-up of 35 months. The presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a CR and improved PFS. In this single-arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at www.clinicaltrials.gov as #NCT02446457.

Long-term stabilization of leptomeningeal disease with whole-brain radiation therapy in a patient with metastatic melanoma treated with vemurafenib: a case report.

We present a patient with metastatic BRAF-mutated melanoma who achieved long-term stabilization of leptomeningeal disease (LMD) with sequential whole-brain radiation therapy and vemurafenib. A 53-year-old woman with melanoma that harbored the BRAF V600E mutation and had that metastasized to multiple lymph nodes, lungs, breast, and subcutaneous tissue had developed symptomatic LMD 16 months after starting vemurafenib treatment despite achieving a substantial response at the existing metastatic sites. Vemurafenib was discontinued for 7 days, she received whole-brain radiation therapy (30 Gy in 10 fractions), and 7 days after completing the radiation therapy, she resumed vemurafenib therapy. The neurologic symptoms improved significantly, and a cerebrospinal fluid examination revealed disappearance of melanoma cells. She remained alive with radiologically stable LMD for at least 18 months after the whole-brain radiation therapy.