Adarsh Vennepureddy

Novel Drugs and Combination Therapies for the Treatment of Metastatic Melanoma.

Metastatic melanoma (MM) still remains as one of the most worrisome cancer known to mankind. In last two decades, treatment of melanoma took a dramatic turn with the discovery of targeted therapy which targets the mutations in mitogen-activated protein kinase (MAPK) pathway and immune checkpoint inhibitors. These new findings have led to emergence of many novel drugs that have been approved by FDA. Targeted therapy drugs such as vemurafenib, trametinib and dabrafenib target the MAPK pathway whereas immunotherapies such as ipilimumab, nivolumab and pembrolizumab block immune checkpoint receptors on T lymphocytes. All these drugs have shown to improve the overall survival in MM. Despite these recent discoveries, treatment of MM remains challenging because of rapid development of resistance to targeted therapy. This review will discuss recently approved drugs and their adverse effects and also shed light on combination therapy in treatment of melanoma.

Anti–PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy

ABSTRACT Introduction: Advanced non-small cell lung cancer (NSCLC) has been conventionally treated with cytotoxic chemotherapy with short-lived responses and significant toxicities. Monoclonal antibodies to programmed death-1 receptor (PD-1) and programmed death ligand 1 (PD-L1) have shown tremendous promise in the treatment of advanced NSCLC in various clinical trials. Areas covered: In this article, we will review the outcomes of various trials of anti-PD-1/anti-PD-L1 antibodies in the treatment of NSCLC. We will also discuss their mechanism of action and toxicities. Expert commentary: Anti-PD-1/PD-L1 antibodies offer several advantages including significant antitumor activity, induction of long lasting responses, and favorable safety profile. Several trials are now being conducted to evaluate their efficacy as first line agents as well as in combination with other agents. More research is also needed to identify other biomarkers, in addition to PD-L1 expression, that could more reliably predict response to these drugs, and aid in better patient selection.

Evolution of ramucirumab in the treatment of cancer - A review of literature.

Ramucirumab is a recombinant human monoclonal antibody and is used in the treatment of advanced malignancies. Its mechanism of action is by inhibiting angiogenesis in tumor cells by targeting the vascular endothelial growth factor receptor 2. United States Food and Drug Administration (FDA) approved it initially in 2014 for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma and metastatic non-small cell lung carcinoma. It was approved by FDA in 2015 for the treatment of advanced colorectal cancer. This manuscript consolidates pre-clinical trials to phase I, II, and III trial data indicating the effects of ramucirumab on different cancer types, which led to its approval. By comparing these clinical trials alongside each other, we can more easily examine the studies that have already been completed, along with currently ongoing studies and potential further areas of interest for this newly approved treatment. This approach makes it convenient to compare dosages, overall survival, adverse events, as well as possible routes for combination therapy with ramucirumab. By compiling results for various oncological malignancies, we can differentiate between treatments that are effective and have the highest incidence of stable disease, and those that do not seem promising. Ramucirumab has been effective in the treatment of various carcinomas and this article outlines other tumors in which this treatment option may be successful.

Bleomycin-induced flagellate erythema in a patient with Hodgkin’s lymphoma – A case report and review of literature

Bleomycin is a glycopeptide used as a chemotherapeutic agent for lymphomas, germ cell tumors, and pleurodesis of malignant pleural effusions. The pulmonary toxicity of bleomycin is well known while the cutaneous side effects are uncommon and varies from generalized hyperpigmentation, sclerodermoid changes, erythema multiformae, and gangrene to flagellate dermatosis. Here we report a characteristic but rare side effect of flagellate erythema, which developed secondary to bleomycin in a 27-year old woman with Hodgkin’s lymphoma after two cycles of treatment with adriamycin, bleomycin, vinblastine, dacarbazine regimen. The rash subsided after discontinuation of bleomycin and treatment with steroids.

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development.

Synchronous Diagnosis of Multiple Myeloma, Breast Cancer, and Monoclonal B-Cell Lymphocytosis on Initial Presentation

The cooccurrence of more than one oncologic illness in a patient can present a diagnostic challenge. Here we report an unusual case of concomitant existence of multiple myeloma, breast cancer, and monoclonal B-cell lymphocytosis on initial presentation. The challenge was to accurately diagnose each disease and stage in order to maximize the therapeutic regimen to achieve cure/remission. Successful management of the patient and increased life expectancy can be achieved by multidisciplinary management and patient-oriented approach in multiple primary malignant synchronous tumors.

Role of cyclin-dependent kinase 4/6 inhibitors in the current and future eras of cancer treatment

Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor to gain Food and Drug Administration (FDA) approval, specifically as monotherapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy and endocrine therapy. Abemaciclib also shares a similar indication with palbociclib for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Trilaciclib use remains largely investigational at this time. However, despite FDA-approval for only metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, all four cyclin-dependent kinase 4/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors. Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma. We discuss the approved indications, current research, and areas of future exploration for palbociclib, ribociclib, abemaciclib, and trilaciclib.

Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia@@@Correction

[This corrects the article DOI: 10.7759/cureus.1096.].

Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia

Myelodysplastic syndrome (MDS) refers to a group of various stem cell disorders, characterized by dysplastic and ineffective production in one or more cell lines. In general, MDS tends to present slowly over months to years and is commonly detected with routine bloodwork by primary care physicians. Patients may be asymptomatic and depending on age, comorbidities and risk classification of MDS may not require aggressive therapy. However, MDS carries the risk of progressing to acute leukemia over time. We present a case of rapidly progressive MDS in a previously healthy middle-aged female, originally presenting and treated as acute leukemia.

Bronchial myeloid sarcoma with concurrent Aspergillus fumigatus infection in a patient presenting with hemoptysis

Myeloid sarcoma (MS) is an extramedullary myeloid neoplasm characterized by proliferation of myeloblasts which can occur in any organ or site. Bronchial and pulmonary involvement, however, is uncommon. We describe a case of bronchial MS in an 81-year-old female with a history of high-grade myelodysplastic syndrome; she was started on treatment few months before, and she presented with fever, cough and profuse hemoptysis. She was found to be pancytopenic with bilateral airspace consolidations, most notably in the right upper and lower lobes, on imaging studies. She was treated with broad-spectrum antibiotics and antifungals without much improvement in her clinical or radiological status. Ultimately, biopsy of the lung lesions showed myeloid sarcoma with concurrent Aspergillus fumigatus infection. Bronchial/pulmonary MS should be considered in the list of differential diagnoses in a patient with a history of myeloid neoplasm and presenting with respiratory related symptoms, as early administration of chemotherapy may help to improve survival rates.