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المؤلفون: Constantin A Dasanu, Andrew S Iskandar, Andrew Hwang
المصدر: Journal of Oncology Pharmacy Practice. 25:1282-1284
مصطلحات موضوعية: Male, musculoskeletal diseases, medicine.medical_specialty, Immune checkpoint inhibitors, macromolecular substances, Pembrolizumab, Antibodies, Monoclonal, Humanized, medicine.disease_cause, Autoimmunity, Polymyalgia rheumatica, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, medicine, Humans, Pharmacology (medical), Adverse effect, Aged, 80 and over, business.industry, Cancer, medicine.disease, Dermatology, Oncology, Polymyalgia Rheumatica, 030220 oncology & carcinogenesis, Joint pain, medicine.symptom, business, 030215 immunology
الوصف: Pembrolizumab is a humanized anti-programmed cell death 1 antibody used for the therapy of several malignancies. While autoimmune adverse events are not uncommon with this agent, they are typically mild and self-limiting. Severe autoimmunity is rare but can be life-threatening. Herein, we describe a unique case of severe proximal muscle weakness and joint pain shortly after beginning therapy with pembrolizumab. Work-up revealed elevated pro-inflammatory markers leading to the diagnosis of polymyalgia rheumatica. Steroids allowed for resolution of the joint pain. We call for awareness of this rare autoimmune toxicity with pembrolizumab.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a01fe0627f0b4f0d9f1093bc5bda47eTest
https://doi.org/10.1177/1078155218800386Test -
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المؤلفون: Constantin A Dasanu
المصدر: Journal of Oncology Pharmacy Practice. 27:205-206
مصطلحات موضوعية: Proto-Oncogene Proteins B-raf, Metastatic melanoma, business.industry, Melanoma, Immune checkpoint inhibitors, medicine.medical_treatment, medicine.disease, Radiation therapy, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Mutation, medicine, Cancer research, Humans, Pharmacology (medical), Neoplasm Recurrence, Local, business, Protein Kinase Inhibitors, 030215 immunology
الوصف: Development of brain metastases during treatment with B-raf/MEK inhibitors for malignant melanoma tends to be more frequent than during immune checkpoint inhibitor therapy. Long-term responders to B-Raf inhibitors with or without MEK inhibition should be monitored very closely clinico-radiologically for a potential relapse. In addition to surgery and/or radiation therapy, single or dual immune checkpoint inhibitor therapy should be started without delay in this setting to ensure a favorable clinical outcome.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0745117e3a020713c5ac6f9cc0441a1fTest
https://doi.org/10.1177/1078155220975079Test -
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المصدر: Journal of Clinical Oncology. 39:e20040-e20040
مصطلحات موضوعية: IgM Monoclonal Gammopathy, Cancer Research, Pathology, medicine.medical_specialty, Peripheral neuropathy, Oncology, business.industry, Medicine, business, medicine.disease, Immunoglobulin light chain, Monoclonal gammopathy of undetermined significance
الوصف: e20040 Background: Monoclonal gammopathy of undetermined significance (MGUS) can be associated with significant neurologic morbidity. Of non-IgM MGUS, types IgG and IgA are most commonly associated with peripheral neuropathy (PN). Methods: With IRB approval, we conducted a retrospective cohort study of consecutive patients with non-IgM type MGUS treated at our institution from 2014-2021. Other conditions potentially causing PN were excluded. Statistical analysis: Descriptive statistics were calculated to characterize the study population, and Relative Risk (RR) of PN was evaluated for selected patient, and disease, related factors. P < 0.05 was defined as statistically significant. Results: During the study period, 94 patients with non-IgM type MGUS were seen and comprised the study population. Twenty-two (23.4%) had evidence of PN. Median age was 74; 82% (18/22 ) were Caucasian; 73% (16/22) were women. 82% (18/22) patients had MGUS type IgG kappa or IgA kappa. We identified only 2 patients with each MGUS kappa light chain (LC) and MGUS IgG lambda. Median M-protein size was 0.11 g/dL, and median free LC value was 6.84 mg/L. Incidence/severity of kidney disease was similar in non-IgM MGUS patients with and without PN (p > 0.05). RR of PN was not found to be significantly different based on race or gender, although there appeared to be a tendency for women to be at higher risk compared to men (RR = 1.98, 95% CI = 0.85 to 4.60, p = 0.114.) Kappa LC restriction was strongly associated with PN (RR = 4.31, 95% CI = 1.58 to 11.78; p = 0.004). Electromyographic (EMG) studies identified 14 patients (64%) with distal symmetric axonal neuropathy (DSAN) and 8 patients (36%) with chronic inflammatory demyelinating polyneuropathy (CIDP). Clinically severe PN was identified in 11 (50%) patients; all were subsequently treated with IVIg therapy. Only 5/11 (45%) patients responded to IVIg, and the responses were only partial and transient. Conclusions: This is the first report, to our knowledge, of a significant association of kappa (as opposed to lambda) LC restriction with PN among patients with non-IgM type MGUS. Further investigation is warranted to explain this finding, elucidate pathophysiology and aid in developing more effective therapeutic options. Pending mechanistic characterization of this association, trials of contemporary agents used to treat other plasma cell disorders may be in order. Final statistical analysis, comparison to published series and significance will be presented.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::61a4a0d5601868286c363785c4c0a5a3Test
https://doi.org/10.1200/jco.2021.39.15_suppl.e20040Test -
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المؤلفون: Juliana Alvarez Argote, Constantin A Dasanu
المصدر: Current Medical Research and Opinion. 34:757-763
مصطلحات موضوعية: Male, Oncology, medicine.medical_specialty, Myeloid, Nonsense mutation, Chronic myelomonocytic leukemia, Frameshift mutation, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Missense mutation, Clinical significance, Aged, business.industry, Myelodysplastic syndromes, Myeloid leukemia, General Medicine, Middle Aged, medicine.disease, Repressor Proteins, medicine.anatomical_structure, Leukemia, Myeloid, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Mutation, Cancer research, Female, business, 030215 immunology
الوصف: ASXL1 gene mutations include nonsense, missense, and frameshift mutations. Although their clinical significance is still debated, they may play an important role in the pathogenesis of several hematologic malignancies.Herein, we offer a comprehensive review on ASXL1 mutations, and link them with survival and clinical outcomes in patients with various myeloid neoplasms. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to February 2016.In acute myeloid leukemia (AML), ASXL1 mutations tend to correlate with older age and male gender, and affect predominantly patients with secondary AML. De novo AML patients with ASXL1 mutations had significantly lower complete remission rates after standard high-dose chemotherapy and shorter survival. In chronic myelomonocytic leukemia and low- or intermediate-risk myelodysplastic syndromes, frameshift and nonsense mutations correlated with shorter survival and a higher risk of leukemic transformation. Overall survival was also shorter in primary myelofibrosis in the presence of ASXL1 mutations.Further research on the role of ASXL1 mutations and therapeutic implications in neoplastic myeloid disorders is stringently needed. Given the relatively high prevalence of ASXL1 mutations, larger studies involving patients affected by these mutations will be feasible in the near future.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::badab17843309f305ffbfbb4f17f2f88Test
https://doi.org/10.1080/03007995.2016.1276896Test -
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المصدر: BBA Clinical
مصطلحات موضوعية: business.industry, Review Article, medicine.disease, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Physiology (medical), Immunology, Molecular Medicine, Medicine, In patient, business, Multiple myeloma, Monoclonal gammopathy of undetermined significance, 030215 immunology
الوصف: Background Multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS), have been linked with several autoimmune conditions in the medical literature. Yet, significance of these associations is not well understood. Methods Herein, we provide a comprehensive literature review on autoimmune disorders identified in patients with MM and MGUS. Most relevant papers were identified via searching the PubMed/Medline and EMBASE databases for articles published from inception until May 1, 2016. Findings Scientific literature on autoimmune conditions in patients with MM and MGUS consists of several case series and a multitude of case reports. Our analysis suggests an increased prevalence of autoimmune conditions in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), including various autoimmune hematologic and rheumatologic conditions among other entities. Conversely, persons with various autoimmune conditions tend to have a higher prevalence of MGUS and MM than the general population. Conclusions Future research is required to explore further the link between MGUS/MM and autoimmune disorders. Inflammation in the setting of autoimmunity may serve as a trigger for MGUS and MM. In addition, a common genetic susceptibility for developing both an autoimmune disease and MM/MGUS might also exist. Autoimmune hematologic and rheumatologic diseases may pose important clinical problems for the MM patients. Therefore, a catalogue of these problems is important so that physicians are able to consider, identify and address them promptly.
Highlights • A comprehensive review linking MM and MGUS with autoimmune disorders • There is increased prevalence of autoimmune conditions in patients with MM and MGUS • Most autoimmune disorders precede the development of plasma cell dyscrasiasالوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47c7b5e5a20f7d32ae48ed32d4151778Test
https://doi.org/10.1016/j.bbacli.2016.05.004Test -
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المصدر: Journal of Oncology Pharmacy Practice. 25:214-216
مصطلحات موضوعية: Male, Oncology, medicine.medical_specialty, Skin Neoplasms, animal structures, Programmed Cell Death 1 Receptor, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Avelumab, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Azathioprine, medicine, Advanced disease, Humans, Immunologic Factors, Pharmacology (medical), Stage (cooking), skin and connective tissue diseases, Aged, Retrospective Studies, Aged, 80 and over, integumentary system, Merkel cell carcinoma, business.industry, Incidence (epidemiology), Antibodies, Monoclonal, virus diseases, Cancer, Immunosenescence, Middle Aged, medicine.disease, Carcinoma, Merkel Cell, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, business, 030215 immunology, medicine.drug
الوصف: Cases of Merkel cell carcinoma have become increasingly more common in the last two decades, and its incidence has been predicted to climb further. Immunosenescence might explain in part the higher Merkel cell carcinoma prevalence in seniors aged 70 and older. This cancer might also be more aggressive in immunocompromised patients. In a subset of immunocompromised Merkel cell carcinoma patients, we identified significant lymphopenia and a more advanced disease stage compared with their immunocompetent counterparts. Time to death in this cohort was much shorter than in immunocompetent subjects, and their likelihood of death from Merkel cell carcinoma was five times higher. Avelumab approval in 2017 represents an important step forward in the therapy of Merkel cell carcinoma. Hopefully, PD1/PDL1 inhibitors will improve survival in immunocompromised Merkel cell carcinoma hosts, traditionally linked with inferior clinical outcomes.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::05efab1639b5bb68456319341af62ba8Test
https://doi.org/10.1177/1078155218785002Test -
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المؤلفون: Constantin A, Dasanu, Michael, Del Rosario, Ion, Codreanu, Yani, Lu, Stephanie, Farrell, David M, Hyams, Steven C, Plaxe
المصدر: Dermatology online journal. 25(2)
مصطلحات موضوعية: Aged, 80 and over, Male, Skin Neoplasms, Time Factors, Middle Aged, Tumor Burden, Carcinoma, Merkel Cell, Survival Rate, Immunocompromised Host, Sex Factors, Chemotherapy, Adjuvant, Humans, Lymph Node Excision, Female, Neoplasm Invasiveness, Radiotherapy, Adjuvant, Aged, Follow-Up Studies, Neoplasm Staging, Retrospective Studies, SEER Program
الوصف: Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed. Compared to Surveillance, Epidemiology, and End Results (SEER) data, our population was entirely Caucasian (100% versus 95%; P=0.11) and male predominant (75% versus 63%; P=0.11). The median age was 76. The patients more often had Tumor-Node-Metastasis (TNM) stage I disease (50% versus 39%; P=0.00003) and a primary tumor size2cm (57.5% versus 34%; P0.01). They received more frequently lymph node dissection (70% versus 63%, P=0.002) compared with the SEER findings. We identified a subset of immunocompromised patients (n=10) who presented with more stage III disease (40% versus 33%; P=0.021). Time to death averaged 290.1 days in this subset versus 618.2 days (P0.001) in immunocompetent patients and their likelihood of death was 5 times higher. As clinical outcomes in MCC patients vary by immunological status, a multidisciplinary tumor-board approach may better optimize individual patient management.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::481e0be08c2aa16db68eccefcf23f085Test
https://pubmed.ncbi.nlm.nih.gov/30865403Test -
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المؤلفون: Constantin A Dasanu, Andrew Hwang, Andrew S Iskandar
المصدر: Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 25(6)
مصطلحات موضوعية: Oncology, Alectinib, medicine.medical_specialty, Lung Neoplasms, Anaplastic Lymphoma, Carbazoles, Re introduction, 03 medical and health sciences, 0302 clinical medicine, Piperidines, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Anaplastic lymphoma kinase, Humans, Pharmacology (medical), Lung cancer, Protein Kinase Inhibitors, business.industry, Interstitial lung disease, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, Female, Non small cell, business, Lung Diseases, Interstitial, 030215 immunology
الوصف: Alectinib is a member of the family of anaplastic lymphoma kinase inhibitors. This agent is effective in the treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung cancer and has excellent blood–brain barrier penetrability. It is generally well tolerated; however, significant toxicities such as interstitial lung disease have been reported. We present herein an instance of interstitial lung disease four weeks into alectinib treatment. Alectinib was held, and the patient showed clinical and radiographic improvement of her interstitial lung disease. Alectinib was then resumed at half dosage without further complications. Prompt recognition of adverse reactions to this targeted agent is paramount. Cessation of therapy may be needed on a case-to-case basis. However, as our case highlights, safe re-introduction of alectinib can be accomplished in some cases.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a323298b76d5d6c70e82147f6f0ec394Test
https://pubmed.ncbi.nlm.nih.gov/30572795Test -
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المصدر: Expert opinion on biological therapy. 19(2)
مصطلحات موضوعية: 0301 basic medicine, Oncology, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Bevacizumab, Clinical Biochemistry, Angiogenesis Inhibitors, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Clinical Trials, Phase II as Topic, Refractory, Internal medicine, Drug Discovery, otorhinolaryngologic diseases, medicine, Meningeal Neoplasms, Humans, Prospective Studies, neoplasms, Retrospective Studies, Pharmacology, business.industry, Atypical meningioma, medicine.disease, nervous system diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, business, medicine.drug
الوصف: Historically, systemic agents had shown limited efficacy in meningioma, at the expense of significant pharmacologic and/or financial toxicity. As meningiomas are highly vascularized, they might derive benefit from antiangiogenic therapy.This review summarizes the literature regarding bevacizumab pharmacology, safety and efficacy in patients with refractory meningioma. We have searched PubMed/Medline database for pertinent articles published from inception to 1 September 2018.Results of two prospective phase II trials, supported by several retrospective cohorts, suggest a clinical benefit for the vascular endothelial growth factor inhibitor bevacizumab in meningiomas refractory to surgery and radiation therapy. This agent has a tolerable toxicity profile and seems more effective in higher-grade histologies and atypical meningioma, although responses in low-grade meningiomas have also been documented. Our conclusions are restricted due to a small size and lack of control in the prospective trials as well as the retrospective design of other studies. Further study of bevacizumab in refractory higher-grade meningiomas seems warranted.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9deec32d310268ec59fa1c75e6ba0f46Test
https://pubmed.ncbi.nlm.nih.gov/30556741Test -
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المؤلفون: Yazeed Samara, Farhad M Limonadi, Omid Hamid, Constantin A Dasanu, Ion Codreanu, Juliana Alvarez-Argote
المصدر: Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 25(3)
مصطلحات موضوعية: Oncology, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Bevacizumab, Angiogenesis, medicine.medical_treatment, Angiogenesis Inhibitors, Brain Edema, Meningioma, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, otorhinolaryngologic diseases, medicine, Meningeal Neoplasms, Humans, Pharmacology (medical), neoplasms, Neovascularization, Pathologic, business.industry, Growth factor, Metastatic Meningioma, medicine.disease, nervous system diseases, Radiation therapy, Vascular endothelial growth factor, Vascular endothelial growth factor A, chemistry, 030220 oncology & carcinogenesis, business, 030215 immunology, medicine.drug, Signal Transduction
الوصف: Effective therapies for relapsed/refractory meningioma after surgery and radiation therapy represent an unmet need. Most meningiomas are highly vascularized tumors and, therefore, potentially amenable to antiangiogenic therapy. Herein, we review comprehensively the scientific literature on systemic therapy options for relapsed, persistent or metastatic meningioma, not amenable to local therapy. Also, this review offers insights into the function of vascular endothelial growth factor/receptor pathway both in health and disease. Further, we address the current status of the preclinical and clinical studies targeting vascular endothelial growth factor/receptor signaling in meningioma. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to 1 February 2018. Vascular endothelial growth factor pathway activation might represent the primary driver of angiogenesis in meningioma. Positive findings of two prospective phase II trials, supported by the results of several retrospective cohorts, suggest a clinical benefit for the vascular endothelial growth factor inhibitor bevacizumab in refractory meningioma. Bevacizumab causes both peritumoral brain edema reduction and true meningioma shrinkage. Patients with WHO grades II–III meningioma appear to benefit more than patients with grade I disease. Similarly, responses have been documented with certain oral targeted anti-vascular endothelial growth factor/receptor agents. Further exploration of the role of vascular endothelial growth factor/receptor inhibitors in refractory meningioma seems warranted.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3407b0f7dfdca4cdb6bcddb3ce2c9c85Test
https://pubmed.ncbi.nlm.nih.gov/30253729Test
