Adebayo Ogunniyi

OBJECTIVE: To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology. DATA SOURCES: A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators(') personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options. DATA SYNTHESIS: Ipilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising. CONCLUSIONS: The treatment landscape in oncology is quickly evolving with the advent of ICIs.

The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

Advancements in the treatment of acute myeloid leukemia (AML) have been sparse during the past several decades, and the disease continues to have a poor prognosis. However, in 2017 alone, four new medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of AML reached the market. Midostaurin, liposomal cytarabine and daunorubicin, enasidenib, and gemtuzumab ogozamicin all showed benefit in respective clinical trials to gain approval for the treatment of AML in various patient populations. Additionally, many phase II and III clinical trials are currently ongoing to assess the safety and efficacy of other potential therapies for the treatment of AML. In this review, we summarize the results of the landmark clinical trials associated with the newly approved agents as well as the current ongoing clinical trials for the treatment of AML. A literature search was performed to retrieve data on agents currently being studied for use. Although the overall prognosis for patients with AML remains poor, the addition of the newly FDA-approved medications is a step in the right direction for a disease state that has proved difficult to treat.

Plerixafor (P), an agent that selectively and reversibly binds to the chemokine receptor CXCR4, has been approved in combination with G-CSF (P + G-CSF) for stem cell (SC) mobilization in patients with multiple myeloma (MM). The goal of this study was to determine the SC collection success rate of P + G-CSF using a clinically relevant outcome defined as the ability to collect at least 5 × 106 CD34+ cells/kg to allow safely two transplants, and identify risk factors impacting SC mobilization. One hundred and thirty-eight patients were mobilized with P + G-CSF upfront following induction. The SC collection success rate was 92.8%. We identified exposure to lenalidomide alone (p = .038), WBC count <4 × 103/mcL prior to mobilization (p = .01) and non-African American race (p = .019), as risk factors for low efficiency by multivariate analysis. This study demonstrates that P + G-CSF is highly efficient in MM patients and provides strong support for its upfront use in SC collection for MM patients.

OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). STUDY SELECTION/DATA EXTRACTION: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified. DATA SYNTHESIS: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL. CONCLUSION: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.