Evidence-based recommendations for induction and maintenance treatment of newly diagnosed transplant-ineligible multiple myeloma patients.

There is increasing evidence regarding the role of various maintenance therapy (MT) strategies after initial induction to treat newly diagnosed transplant-ineligible patients with MM. We reviewed the literature on available regimens for patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). Lenalidomide (R)-based regimens are still the front-line therapy, but there is an increasing use of bortezomib-based regimens. The MT regimen is mainly based on the initial induction regimen. MT has shown survival benefits compared with patients without maintenance therapy. The most common adverse effects of MT include anemia, neutropenia, thrombocytopenia, infections, and peripheral neuropathy. In conclusion, induction followed by maintenance based on lenalidomide, bortezomib, ixazomib, or daratumumab-based regimens has shown promising results. Therefore, it is essential to conduct more clinical trials to better understand the role of MT in the treatment of NDMM patients who are not candidates for autologous stem cell transplantation.

Pneumonitis and cellular immunodeficiency triggered by the CDK 4/6 inhibitor Abemaciclib.

Breast cancer is the second most common cancer amongst women in the United States following non-melanoma skin cancer. There were an estimated 276,480 new cases and 42,170 deaths in 2020. The lifetime risk for developing breast cancer in females is about 13%. In the United States this year approximately 284,200 people out of which 281,550 women and 2,650 men, will be diagnosed with invasive breast cancer. In recent years, treatment options with novel mechanisms have emerged. Cyclin dependent kinase (CDK) 4/6 inhibitors, namely palbociclib, ribociclib and abemaciclib, are relatively new targeted therapies for treating breast cancers express estrogen receptors (ER) and/or progesterone receptors (PR). CDKs are important regulatory enzymes in cell cycle transitions and cell division. Selective inhibition of CDK4/6 causes cell cycle to arrest in the G1 phase, resulting in reduced cell viability and tumor response. Abemaciclib is the only one approved as monotherapy. Palbociclib and ribociclib must be used as adjunctive therapy to endocrine therapy such as tamoxifen, aromatase inhibitors or fulvestrant. Common side effects include neutropenia, thrombocytopenia, fatigue, nausea, and vomiting. A black box warning for all CDK inhibitors is a rare but possibly fatal severe inflammation of the lungs, called pneumonitis. We present a fatal case of severe pneumonitis with superimposed fungal respiratory infection in the setting of hypogammaglobulinemia in a 65-year-old female with metastatic ER and PR positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer who received abemaciclib.

Checkpoint inhibitors: literature review of new treatments for hepatocellular carcinoma.

OBJECTIVE: To systematically review the ongoing progress of effective treatment of advanced hepatocellular carcinoma (HCC), mainly focusing on immune checkpoint inhibitors (ICPI) as monotherapy and combination therapy. BACKGROUND: HCC in general has a poor prognosis; particularly in the advanced stage. For more than 10 years, the treatment with multikinase inhibitors was the first line treatment. Before the introduction of checkpoint inhibitors, very few treatments were available for patients with hepatocellular cancer in the advanced stage, especially in metastatic and unresectable disease. METHODS: We performed an extensive search of the ongoing and published clinical trials in the English written literature concerning of HCC with immune checkpoint inhibition when compared to first line chemotherapy. CONCLUSIONS: The treatment paradigm for advanced stage HCC has significantly changed recently with the introduction of immunotherapy; based on existing research, there is new era for HCC treatment which will positively affect the outcome in a malignancy that did not see therapy advancement for more than a decade. Monoclonal antibodies against programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1), such as nivolumab and pembrolizumab appear to be a promising therapeutic option in HCC. This review outlines immunotherapy that has been approved, and what inhibitors are under investigation for patients with advanced stage HCC.

Response of advanced cutaneous squamous cell carcinoma to immunotherapy: case report.

The most common cancer in the United States is non-melanoma skin cancer. Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer after basal cell carcinoma. It develops in the middle and outer layers of the skin. Its precursor is actinic keratosis, which can progress to squamous cell carcinoma in situ, invasive cSCC, and finally metastatic cSCC. About 20% of non-melanoma skin cancers are squamous cell and the remaining 80% are basal cell. Unlike basal cell, squamous cell carcinoma has the propensity to metastasize. This commonly occurs with squamous cell carcinoma (SCC) thicker than 2 millimeters. The risk of metastasis and local recurrence increases with 6 mm thickness and desmoplasia. The risk factors are excessive sun or ultraviolet light (tanning beds) exposure, immunosuppression (either having a weakened immune system or taking immunosuppressive therapy) and fair skin. Therefore, it most commonly affects skin in the head and neck area such as scalp, ears, lips, face, neck or the back of the hands. The treatment for local cutaneous squamous cell cancer is mainly surgery; excisional surgery, Moh's surgery, cryosurgery, curettage and electrodessication, laser surgery or radiation therapy, photodynamic therapy or topical agents such as fluorouracil or imiquimod. However, cSCC that is locally advanced, such as involvement of regional lymph nodes, or has metastasized to distant organs or tissue, is not amenable to surgery or radiation alone. Immunotherapy with cemiplimab, a programmed cell death 1 (PD-1) inhibitor, is a US Food and Drug Administration (FDA) approved therapeutic option for locally advanced and metastatic cSCC for patients who are not candidates for or whose disease is not susceptible to curative surgery or radiation therapy. Cemiplimab is a humanized recombinant immunoglobulin monoclonal antibody that binds to and blocks PD-1 receptor found on T cells inhibiting T-cell proliferation and cytokine production. We present a case of locally advanced cSCC with regional lymph nodes metastases, which achieved clinical remission, utilizing a unique approach of therapy combining a checkpoint inhibitor, Cemiplimab and radiotherapy.

Use of Immunotherapy in Extensive-Stage Small Cell Lung Cancer.

Lung cancer is a leading cause of cancer death in the United States and around the world. Approximately 13% of lung cancers are small cell lung cancer (SCLC). SCLC is generally classified as a limited-stage and extensive-stage disease depending on the extent of involvement. For patients with the extensive-stage disease, until recently, chemotherapy alone has been the recommended treatment, although radiotherapy could be used in select patients for palliation of symptoms. The standard of care for extensive-stage SCLC is platinum doublet chemotherapy with either cisplatin or carboplatin in combination with etoposide. Even though first-line therapy has an initial response rate of 60-80%, the prognosis is poor, with overall survival of 10-12 months. The only FDA-approved second line of therapy is topotecan, approved both as an intravenous formulation as well as an oral formulation, with response rates of 6-12% in chemorefractory disease and 15-37% in chemosensitive disease. Immunotherapy has recently been approved as a first-line agent in metastatic SCLC in combination with chemotherapy. It is also approved as a third-line agent in metastatic SCLC after the failure of two chemotherapy regimens. The FDA approved four drugs, two of them being PD-1 inhibitors (pembrolizumab, nivolumab), and two of them being PD-L1 inhibitors (atezolizumab and durvalumab) in SCLC. This review article summarizes the significance of immunotherapy in the treatment of extensive-stage SCLC, its side effects, and limitations.

Recent Advances and Therapeutic Options in Lambert-Eaton Myasthenic Syndrome.

Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune-mediated neurological disorder that manifests as muscle fatigue, diminished tendon reflexes, with symptoms of cholinergic overactivity. It can be associated with certain neoplastic conditions, the most common being small cell lung carcinoma (SCLC). The basic pathophysiology involved is antibody-mediated targeting of voltage-gated calcium channels (VGCC), which decreases the release of acetylcholine in the synaptic junction. Multiple treatment options have been introduced in the past and, recently, a new drug, amifampridine, has been approved by the Food and Drug Administration (FDA) for the treatment of weakness associated with these patients. We summarize this newly introduced drug with a brief description of other treatment options available.

Paraneoplastic syndromes in lung cancer and their management.

Paraneoplastic syndromes are most frequently associated with lung cancer. This review considers a variety of paraneoplastic syndromes associated with lung cancer and discusses their pathophysiology, clinical features and management options.

Carotenoids and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem around the world, especially in developed countries. NAFLD includes all cases of fatty liver disease from simple steatosis to cirrhosis, without excessive alcohol intake, use of steatogenic medication or hereditary disorders. Pathogenesis is associated with dietary high fat intake, decreased free fatty acid (FFA) oxidation, increased hepatic lipogenesis and lipolysis from the adipose tissue. These metabolic alterations contribute to the hepatic fat accumulation. Consequently, stimulated oxidative stress and inflammation play a major role in hepatocellular damage. Therefore, antioxidant and anti-inflammatory agents may have a role in the prevention of this disease. Carotenoids are potent antioxidant and anti-inflammatory micronutrients, which have been investigated in the prevention and treatment of NAFLD. The main sources of the carotenoids are fruits and vegetables. In this article we review the potential role and possible molecular mechanism of carotenoids in NAFLD.