Hanna, Kirollos S.

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin’s lymphomas that is generally classified as an aggressive lymphoma requiring front-line chemo-immunotherapy with stem cell rescue. Despite effective treatment, many patients relapse or are refractory to front-line therapy. In addition, these patients may also develop drug resistance requiring novel modalities for subsequent lines. Bruton’s tyrosine kinase inhibitors have demonstrated a well-tolerated safety and efficacy profile across several B-cell malignancies. Ibrutinib, acalabrutinib, and zanubrutinib are FDA-approved as treatment options for patients with Mantle cell lymphoma following one prior line of therapy. Various factors should be considered which include the adverse event profile of these agents and ability to adhere to therapy. In this article, we review the role of Bruton’s tyrosine kinase inhibitors for the management of Mantle cell lymphoma and review the clinical pharmacology, pharmacokinetics, safety and efficacy, and future directions.

Renal cell carcinoma is a common malignancy of the genitourinary system and is the eight most common cancer type in the United States. The overall incidence of renal cell carcinoma appears to be increasing but death rates have been declining. Patients with poor risk, advanced disease have a two-year survival rate of approximately 7%. Prior to the advent of tyrosine kinase inhibitors, anti-vascular endothelial growth factor antibodies, mammalian target of rapamycin inhibitors, and checkpoint inhibitors, IFN-α and high-dose IL-2, were standard of care treatment options but, conversely, their use is now limited to select patients. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for renal cell carcinoma as they mark a new era in the treatment of advanced or relapsed setting. Nivolumab, pembrolizumab, avelumab, ipilimumab, and atezolizumab all play a role in management of disease as either monotherapy or in combination with other agents. Ongoing clinical trials are ongoing to further assess the benefits of inducing cellular immunity in the treatment of renal cell carcinoma. In this article, the available data on immune checkpoint inhibitors for the treatment of advanced or relapsed renal cell carcinoma and their place in therapy are reviewed.

Chronic lymphocytic leukemia is one of the most common lymphoid malignancies. Often treatment modalities are tailored to individual patients based on age, presence of comorbidities and cytogenetics. The advent of ibrutinib has significantly changed the management of the disease in all patient groups and has had the largest impact on clinical practice to date. Over the last 15 years, a series of trials have established that chemoimmunotherapy improves both progression-free survival and overall survival compared to chemotherapy alone. Despite its proven role, efficacy of ibrutinib has not been well established in young, fit patients and in comparison with standard care and as combination therapy with other agents such as venetoclax. New data have strengthened the role of ibrutinib in the front-line setting and establish its place in therapy. In addition, combination therapies are geared to achieve negative minimal residual disease and allow patients to potentially be off of therapy. The management of this leukemia has extensively changed over the past years, and this review article will aim to highlight key trials that have changed practice and led to guideline updates. It is not unlikely that treatment modalities will continue to improve in light of new data.

Urothelial Carcinoma (UC) is the second most common malignancy of the genitourinary system and is the sixth most common cancer in the USA. Over a decade prior to 2016, the standard of care for early disease consisted of transuretheral resection of the bladder tumor with or without intravesicular chemotherapy or immunotherapy. Systemic chemotherapies such as gemcitabine and cisplatin combinations or dose-dense methotrexate, vinblastine, doxorubicin, cisplatin were reserved for recurrent, muscle-invasive, advanced or metastatic disease. Novel treatment approaches for UC have significantly impacted the management of patients. In 2016–2017, five immune checkpoint inhibitors marked a new paradigm in the treatment of UC for patients with advanced or metastatic disease or who are unable to tolerate platinum-based chemotherapy. Most recently, the U.S. Food and Drug Administration set restrictions on two commonly utilized checkpoint inhibitors, atezolizumab and pembrolizumab, in the first-line setting in patients with UC due to decreased survival associated with low expression of the protein programmed death ligand 1. Furthermore, Breakthrough Therapy Designations have been granted for enfortumab vedotin and erdafitinib for patients following platinum-based chemotherapy and those with fibroblast growth factor receptor mutated UC, respectively. Additional updates include dose-dense gemcitabine and cisplatin for muscle-invasive bladder cancer and preoperative checkpoint blockade. This article will review the available data on updates in the treatment of UC and future direction of therapies.

Urothelial carcinoma ( UC ) is the second most common malignancy of the genitourinary system and the sixth most common cancer in the United States. The overall incidence of UC appears to be on the decline, but death rates have remained stable. Stage IV metastatic disease is associated with only a 5% survival rate at 5 years. Gemcitabine and cisplatin combinations or dose‐dense methotrexate, vinblastine, doxorubicin, and cisplatin are the preferred regimens for individuals with advance, metastatic disease and a good performance status and organ function. Second‐line therapies in this setting are limited. During the course of 1 year, five immune checkpoint inhibitors were approved for treatment of cancers in the locally advanced or metastatic setting: atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for UC . Based on the limited data, pembrolizumab and atezolizumab may be the drugs of choice, as they are supported by the most influential data to date; however, further research is warranted. Ongoing clinical trials will further assess the benefits of inducing cellular immunity in the treatment of UC . These therapies mark a new landscape in the treatment of UC . In this article, the available data on immune checkpoint inhibitors for the treatment of locally advanced or metastatic UC and their place in therapy are reviewed.

Pembrolizumab, a programmed cell death protein 1 (PD‐1) inhibitor, is a humanized monoclonal antibody used in the treatment of metastatic or unresectable melanoma and advanced non–small cell lung cancer (NSCLC). We hereby report a case of pembrolizumab‐induced uveitis to increase practitioner awareness. A 78‐year‐old woman presented with onset of panuveitis after initiation of pembrolizumab therapy for metastatic melanoma. The patient received three cycles of therapy every 21 days, during which her symptoms progressively worsened. She was treated with topical and systemic corticosteroids, and further pembrolizumab was discontinued despite a good response to therapy. Pembrolizumab has been associated with rapid onset of ocular inflammation and uveitis. PD‐1 inhibitors mediate a T‐cell response against cancer cells; however, autoimmune complications have been reported. Incidence of pembrolizumab‐induced uveitis is reported to be < 1%. To date, three cases have been reported since its Food and Drug Administration approval in September 2014. Uveitis, if left untreated, may lead to permanent vision loss and ocular damage. Cases of immune‐mediated uveitis have been reported with cancer immunotherapies. Oncologists and ophthalmologists should be aware of this complication. With the increasing targeted pharmaceuticals in oncology, effective management of adverse events is necessary to ensure patient safety and optimal outcomes.