Sami Ibrahimi

Do proton pump inhibitors modulate the efficacy of anti-PD-1/PD-L1 therapy? A retrospective study

Cancer immunotherapy is one of the most rapidly evolving fields in medicine. Immune checkpoint inhibitors act by releasing a molecular brake-like programmed death-1 (PD-1) or its ligand PD-L1, thus enabling the immune system to attack and destroy cancer cells. These drugs are used to treat a number of patients with a wide variety of solid tumors including metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial cancer, head and neck cancer, gastroesophageal cancer, hepatocellular carcinoma, and hematologic malignancies like Hodgkin’s lymphoma. Currently, there are several Food and Drug Administration-approved immune checkpoint inhibitors that target the PD-1/PD-L1 pathway: nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. A healthy immune system is capable of destroying tumor cells. However, tumor cells and antigen-presenting cells often express immune checkpoints like PD-L1 on their surface. When PD-L1 molecules bind to PD-1 molecules on T cells, they inhibit T-cell function and the tumor cells evade immune surveillance. Immune checkpoint inhibitors directed against PD-1/PD-L1 restore immune function by inhibiting those inhibitory molecules. Unbalancing of immune system leads to immunerelated adverse events (IRAEs) in some patients treated with anti-PD-1/PD-L1 therapy. Diarrhea/colitis and pneumonitis are frequent causes of hospitalization among patients receiving immunotherapy. Grade 3/4 immune-mediated diarrhea/colitis are seen in approximately 1 to 2% of cases, while the incidence of grade 3/4 pneumonitis have been reported in up to 1% patients. Other IRAEs include endocrinopathies, hepatotoxicity, renal toxicity, and dermatologic toxicity. Recently, the composition of gut microbiome has been an active area of interest in cancer immunotherapy. Gopalakrishnan et al. analyzed the oral and fecal microbiome in melanoma patients treated with anti-PD-1/PD-L1 therapy and showed that there is a significant difference in the diversity and composition of gut microbiome among responders vs. nonresponders. In their study, they showed that the within sample diversity of gut microbiome, which takes into account both the number of different species as well as their relative distribution, was significantly higher among responders compared to non-responders. Proton pump inhibitors (PPIs) are commonly used around the world for different indications including gastro-esophageal reflux disease and prevention and treatment of peptic ulcer disease. In 2013, esomeprazole (PPI), was the second largest drug in the US in terms of revenue. A recent study by Imhann et al. found that PPI use was associated with a decreased diversity of the gut microbiome as compared to the non-users. Based on the information presented above, it was hypothesized that cancer patients receiving anti-PD-1/ PD-L1 therapy, while taking PPIs concurrently, will have a different outcome compared to those who are not using PPIs. A retrospective review was performed on 158 patients aged 18 years or older, treated at the University of Oklahoma Health Sciences Center with anti-PD-1/PD-L1 therapy between 2014 and 2016. PPI use was assessed based on medical record review of prescribed and self-reported medications. This study was approved by the institutional review board. Our primary objective was to investigate whether the

Degloving the Feet: A Severe Case of Hand-Foot Syndrome After Induction Chemotherapy

A 21-year-old man with relapsed refractory FLT3-mutated acute myeloid leukemia (AML) received third-line induction chemotherapy with clofarabine, cytarabine, and sorafenib. Within 7 days, he started having hand and foot pain with erythema. Over the next few days, his symptoms progressed, and he developed large flat bullae and severe desquamation of his feet (Figures 1 and 2). He was diagnosed with grade 3 hand-foot syndrome. He was unable to walk for 1 week due to severe pain and swelling, but his symptoms gradually resolved within 3 weeks. Treatment consisted of oral pyridoxine, topical steroids, and other supportive measures, including ice packs, leg elevation, avoidance of friction, and topical creams. Palmar-plantar erythodysesthesia, also known as handfoot syndrome (HFS), is a known chemotherapy complication. The condition is usually self-limited, resolving within a few weeks of stopping the culprit medication. HFS has been commonly reported with cytarabine and sorafenib but is less common with clofarabine. Grade 3 or higher HFS occurred in 3% of patients receiving a combination of clofarabine and cytarabine as induction therapy for AML. The severe HFS in this patient could be attributed to any of the 3 medications he received or the cumulative effect of the combination.

Ibritumomab tiuxetan (Zevalin) and elevated serum human anti-murine antibody (HAMA)

Ibritumomab Tiuxetan (Zevalin) is an anti CD-20 murine monoclonal antibody linked to the radio-isotope 90-yttrium (90Y) by the chelator Tiuxetan. It is FDA approved for treatment of relapsed low grade or follicular B-cell Non-Hodgkins Lymphoma (NHL) or newly diagnosed follicular NHL following an initial response to first-line chemotherapy. Patients may develop Human Anti-Murine Antibodies (HAMA), following exposure to murine antibodies. There is a concern for development of hypersensitivity reactions with Ibritumomab, especially in patients with an elevated HAMA titer. Here we describe a case of a 66 year old male with elevated HAMA titer successfully treated with Zevalin without any hypersensitivity reactions. Existing literature supports our observation that Zevalin can be safely used in most patients with elevated HAMA titers.

Extranodal Marginal Zone Lymphoma of the Central Nervous System

Abstract Extranodal marginal zone lymphoma of the central nervous system (CNS EMZBL) is a rare disease. We present a review of the literature and describe its presentation, differential diagnosis, treatment options, and outcomes. Systematic search of PubMed, Medline, and Embase databases via the Ovid engine for primary articles and case reports yielded 37 unduplicated peer‐reviewed articles of CNS EMZBL. We identified 69 cases in these articles and 1 unreported case at our institution, which were included for this reviews analysis. Median age at diagnosis was 55 years (range, 18‐78 years), with a female preponderance of 77% (n = 54). Most common presenting symptoms were headache in 43% (n = 30), seizures in 31% (n = 22), and visual defects in 27% (n = 19). The most common treatment modalities were localized therapies, which were provided to 67% (n = 47) of cases. These included radiotherapy in 27% (n = 19), radiotherapy with surgery in 24% (n = 17), and surgery alone in 16% (n = 11). Ninety percent (n = 63) of patients had a median follow‐up of 23 months. Complete remission was experienced by 77% (n = 49) patients, and 22% (n = 14) were alive with disease. Three patients had evidence of relapse, and one patient died. CNS EMZBL is an indolent, low‐grade, radiosensitive lymphoma with good treatment outcomes and prognosis. It is an important differential to consider in extra‐axial dural‐based masses. Individualized management plans, with preference given to localized treatment options, should be considered after factoring in the site and extent of disease, its resectability, and the expected adverse effects of systemic therapy.