21 results on '"Re challenge"'
Search Results
2. Re-challenge of Platinum-based Chemotherapy for Platinum-refractory Patients with Recurrent or Metastatic Head and Neck Cancer: Claims Data Analysis in Japan
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Tatsunori Murata, Sari Mishina, Hirokazu Kaneko, Makoto Tahara, Issei Doi, and Shinji Takai
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,chemistry.chemical_element ,Disease ,chemotherapy ,lcsh:Computer applications to medicine. Medical informatics ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Platinum resistance ,medicine ,Re challenge ,Chemotherapy ,business.industry ,Health Policy ,Head and neck cancer ,Public Health, Environmental and Occupational Health ,Cancer ,claims data ,Retrospective cohort study ,platinum-refractory ,medicine.disease ,female genital diseases and pregnancy complications ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,lcsh:R858-859.7 ,head and neck cancer ,business ,Platinum ,re-challenge - Abstract
**Background:** The role of platinum rechallenge in head and neck cancer (HNC) has not yet been fully evaluated. **Objectives:** It is our goal to assess the real-world treatment patterns and usefulness of platinum rechallenge in patients with platinum-refractory recurrent or metastatic HNC receiving platinum rechallenge. **Methods:** This is a retrospective study using data from a Japanese hospital claims database stored in electronic hospital information systems. Patients with HNC or undefined histology with an HNC diagnosis using the disease code, between January 1, 2013 and September 30, 2016, were included. Patients diagnosed with other malignancies on or before the initial diagnosis of HNC and those without cancer stage information in the database were excluded from the study. **Results:** A total of 43 994 patients were identified from the database as HNC patients. Of those, in patients who had cancer progression within 6 months after platinum-based chemotherapy administered for primary or recurrent disease (N=842), the median treatment duration of platinum rechallenge for platinum refractory patients was only 1 cycle. The second-line treatment continuation rate at 6 months was 20.1% for patients who received platinum rechallenges and 32.8% for those who received non–platinum-based regimens. **Conclusions:** The findings from this study of data from routine clinical practice suggest that the benefit of platinum rechallenge in a platinum-refractory setting would be limited.
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- 2020
3. Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital
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Edward Silva, Paul Stephenson, Melanie Higgins, and Barbara Hammer
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medicine.medical_specialty ,RC435-571 ,RM1-950 ,Neutropenia ,agranulocytosis ,03 medical and health sciences ,0302 clinical medicine ,neutrophils ,Intervention (counseling) ,medicine ,Re challenge ,Case Series ,Intensive care medicine ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Clozapine ,Psychiatry ,granulocyte-colony-stimulating factor ,clozapine ,seclusion ,antipsychotic agents ,medicine.disease ,forensic ,030227 psychiatry ,Granulocyte colony-stimulating factor ,schizophrenia ,Schizophrenia ,lithium ,Treatment resistant schizophrenia ,Therapeutics. Pharmacology ,Psychology (miscellaneous) ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia; however, its use is prohibited following neutropenias. We review neutrophil biology as applied to clozapine and describe the strategies to initiate clozapine following neutropenia used in a case series of 14 consecutive patients rechallenged in a United Kingdom (UK) high-secure psychiatric hospital. We examine outcomes including the use of seclusion and transfer. Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using this routinely collected clinical data, we describe the patient characteristics, causes of neutropenia, the strategies used for rechallenging with clozapine and clinical outcomes. Results: Previous neutropenias were the result of benign ethnic neutropenia, clozapine, other medications and autoimmune-related. Our risk mitigation strategies included: granulocyte-colony stimulating factor (G-CSF), lithium and watch-and-wait. There were no serious adverse events; at follow up half of the patient’s had improved sufficiently to transfer them to conditions of lesser security. There were dramatic reductions in the use of seclusion. Conclusion: Even in this extreme group, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients. This requires careful planning based on an understanding of neutrophil biology and the aetiology of the specific episode of neutropenia.
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- 2021
4. Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation
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Ou Yamaguchi, Kosuke Hashimoto, Atsuto Mouri, Kyoichi Kaira, Hiroshi Kagamu, Fuyumi Nishihara, Yoshitake Murayama, Ayako Shiono, Kunihiko Kobayashi, and Yu Miura
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Adult ,Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Afatinib ,Antineoplastic Agents ,Toxicology ,Erlotinib Hydrochloride ,03 medical and health sciences ,Egfr tki ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Pharmacology (medical) ,Re challenge ,In patient ,Treatment Failure ,Lung cancer ,Protein Kinase Inhibitors ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,business.industry ,Middle Aged ,medicine.disease ,ErbB Receptors ,Treatment Outcome ,030104 developmental biology ,Oncology ,Egfr mutation ,030220 oncology & carcinogenesis ,Mutation ,Cancer research ,Female ,Non small cell ,Previously treated ,business ,medicine.drug - Abstract
Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure.From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study.The overall response rate (ORR) and disease control rate (DCR) of afatinib as re-challenge were 17.0% and 79.2%, respectively. The median time on treatment of 1st generation EGFR-TKI (1st TKI) was 14 months. By multivariate analysis, smoking, performance status (PS), and time on treatment of 1st TKI with more than 10 months were confirmed to be independent prognostic factors predicting a worse progression-free survival (PFS), and significant prognostic markers for overall survival (OS) were PS and time on treatment of 1st TKI with more than 10 months, especially in patients with exon 19 deletion.Re-challenge of afatinib was identified as one of the therapeutic options after 1st TKI failure in the patients with advanced NSCLC harboring EGFR mutation when the time of treatment by prior 1st TKI is more than 10 months.
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- 2019
5. Resolution of epoetin‐induced pure red cell aplasia, successful re‐challenge with roxadustat
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Jianing Ni, Xiaomeng Lin, Yunzhou Wu, and Xudong Cai
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Drug ,medicine.medical_specialty ,media_common.quotation_subject ,anti‐erythropoietin antibody ,Clinical Biochemistry ,Pure red cell aplasia ,unusual case ,Disease ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Letter to the Editors ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Re challenge ,Letter to the Editor ,media_common ,biology ,roxadustat ,business.industry ,Biochemistry (medical) ,Roxadustat ,Hematology ,General Medicine ,medicine.disease ,haemoglobin ,pure red cell aplasia ,Erythropoietin ,biology.protein ,Antibody ,Complication ,business ,030215 immunology ,medicine.drug - Abstract
The application of erythropoietin (EPO) can bring about a rare but serious complication called anti‐EPO antibody‐mediated pure red cell aplasia (PRCA). Once the disease is diagnosed, EPO administration should be stopped immediately. However, after the removal of the anti‐EPO antibody, treating anaemia in these patients with chronic renal disease with EPO therapy is difficult, as restarting EPO therapy risks the recurrence of anti‐EPO antibody‐mediated PRCA. A 26‐year‐old man with anaemia related to renal failure, who was administered recombinant human EPO subcutaneously, developed anti‐EPO antibody‐mediated PRCA. After removal of antibodies by treatment with corticosteroids and cyclosporine, therapy for anaemia of chronic renal disease with roxadustat achieved good results. Roxadustat is a new type of drug for the treatment of anaemia, and it can stimulate endogenous EPO within or near the physiologic range and increase haemoglobin levels.
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- 2020
6. Literature meta-analysis about the efficacy of re-challenge with PD-1 and PD-L1 inhibitors in cancer patients
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Elisa Gobbini, Matteo Giaj Levra, Julie Charles, Denis Moro-Sibilot, Anne-Claire Toffart, Marie-Thérèse Leccia, CHU Grenoble, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Léon Bérard [Lyon], and CCSD, Accord Elsevier
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Lung Neoplasms ,[SDV]Life Sciences [q-bio] ,Programmed Cell Death 1 Receptor ,Immune checkpoint inhibitor ,B7-H1 Antigen ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Carcinoma, Non-Small-Cell Lung ,Neoplasms ,Re challenge ,Melanoma ,Aged, 80 and over ,biology ,Hazard ratio ,Hematology ,General Medicine ,Middle Aged ,Progression-Free Survival ,3. Good health ,[SDV] Life Sciences [q-bio] ,Treatment Outcome ,030220 oncology & carcinogenesis ,Meta-analysis ,Toxicity ,Retreatment ,Female ,Anti-programmed cell death ligand 1 ,Adult ,medicine.medical_specialty ,Re-challenge ,03 medical and health sciences ,Young Adult ,Internal medicine ,PD-L1 ,Anti-programmed cell death protein 1 ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Aged ,business.industry ,Solid cancer ,Cancer ,medicine.disease ,030104 developmental biology ,biology.protein ,business - Abstract
Summary Introduction Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy. Methods Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/anti-PD-L1 were collected. Results Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, P = 4.10−4) and disease control rates (73% versus 52%, P = 7.10−3) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found (P = 3.10−1). The PFS upon the first ICPi (PFS1) was longer than after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, P = 2.10−3). A longer PFSR was obtained in patients with a longer PFS1 (P = 6.10−3), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, P = 2.10−3), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, P = 1.10−3). Discussion Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.
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- 2020
7. Case of pembrolizumab-induced myocarditis presenting as torsades de pointes with safe re-challenge
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Daniel Jeong, Dae Hyun Lee, Michael G. Fradley, Jessica Huang, Merna Armanious, and Mihaela Druta
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Adult ,Myocarditis ,Immune checkpoint inhibitors ,Torsades de pointes ,Pembrolizumab ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Torsades de Pointes ,medicine ,Humans ,Pharmacology (medical) ,Re challenge ,business.industry ,medicine.disease ,Cardiotoxicity ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Sarcoma ,business ,Programmed death - Abstract
Introduction Pembrolizumab is an immune checkpoint inhibitor targeting the programmed death receptor with clinical effect on multiple malignancies including sarcoma. Associated cardio-toxicities include myocarditis, cardiomyopathy, heart failure, and arrhythmias. Although in most cases of immune checkpoint inhibitor cardiotoxicity the offending agent is discontinued, we report a case of successful and safe re-challenge with a checkpoint inhibitor in a patient with mild myocarditis. Case report We describe a 37-year-old female with alveolar soft part sarcoma, metastatic to the lungs on cycle 13 of pembrolizumab who presented with dyspnea, cough, and vague chest discomfort. Telemetry showed bigeminal bradycardia that transitioned to self-terminating torsades de pointes. Cardiac MRI showed subtle patchy T2 signal increase within the left ventricular septum without late gadolinium uptake, suggesting mild focal myocarditis. Management and outcome: The patient was started on a steroid taper without additional arrhythmias. We have re-challenged the patient who safely tolerated re-challenge with pembrolizumab despite an episode of torsades de pointes and documented myocarditis. She continues to receive pembrolizumab at seven months after the initial event without further cardiovascular events. Discussion To the best of our knowledge, this is the first reported case of successful re-challenge of pembrolizumab after an episode of myocarditis. In patients with mild myocarditis and no evidence of left ventricular dysfunction, re-challenge may be a viable option. However, close monitoring for the development of heart failure, cardiomyopathy, or serious arrhythmias is necessary to ensure patient safety.
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- 2020
8. A case of non-small cell lung cancer with long-term response after re-challenge with nivolumab
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Tetsuya Oguri, Yutaka Ito, Tomoko Tajiri, Norihisa Takeda, Hirotsugu Ohkubo, Ken Maeno, Akio Niimi, Satoshi Fukuda, Kensuke Fukumitsu, Masaya Takemura, Yoshihiro Kanemitsu, and Keima Ito
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Pulmonary and Respiratory Medicine ,Oncology ,PD-L1 ,medicine.medical_specialty ,medicine.medical_treatment ,Case Report ,03 medical and health sciences ,Immune checkpoint inhibitors ,0302 clinical medicine ,Internal medicine ,medicine ,Re challenge ,Lung cancer ,lcsh:RC705-779 ,Chemotherapy ,biology ,business.industry ,lcsh:Diseases of the respiratory system ,medicine.disease ,Radiation therapy ,Long term response ,Nivolumab ,030228 respiratory system ,030220 oncology & carcinogenesis ,biology.protein ,Non small cell ,business - Abstract
A 76-year-old man was admitted to our hospital with cough and dyspnea. He was diagnosed with advanced lung cancer. Nivolumab was given as second-line treatment, cytotoxic chemotherapy was given as third-line treatment, and nivolumab re-challenge was given as fourth-line treatment. Thereafter, 41 chemotherapy courses were administered over 2 years. Currently, he is being followed with no recurrence at least 10 months after treatment. Thus, the case of a patient with advanced lung cancer who was previously unsuccessfully treated with nivolumab and then demonstrated a long-term clinical response to a re-challenge with nivolumab after cytotoxic chemotherapy and radiation therapy is presented. Keywords: Lung cancer, Nivolumab, Immune checkpoint inhibitors, PD-L1
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- 2019
9. Re-challenge chemotherapy in patients with sensitive relapse small-cell lung cancer and interstitial lung disease
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Hidekazu Suzuki, Yuki Hara, Satomu Morita, Naoko Morishita, Norio Okamoto, Ayako Tanaka, Satoshi Tanaka, Shingo Nasu, Tomonori Hirashima, Kazunori Moriizumi, Hiromune Takada, and Takayuki Shiroyama
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Pulmonary and Respiratory Medicine ,Oncology ,Chemotherapy ,medicine.medical_specialty ,Exacerbation ,business.industry ,medicine.medical_treatment ,Interstitial lung disease ,respiratory system ,medicine.disease ,respiratory tract diseases ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,In patient ,Re challenge ,Original Article ,Non small cell ,business ,Lung cancer ,Etoposide ,medicine.drug - Abstract
Background: Treatment modalities for small-cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD) are limited. Although re-challenge with first-line chemotherapy can be effective for sensitive relapse SCLC, its safety and efficacy are uncertain in cases with ILD. This study aimed to investigate both the efficacy and safety of re-challenge chemotherapy in patients with sensitive relapse SCLC with ILD. Methods: Patients with sensitive relapse SCLC with ILD who received re-challenge chemotherapy were studied retrospectively. Sensitive relapse was defined as a treatment-free interval (TFI) of more than 60 days after first-line platinum-based treatment. The endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Re-challenge platinum and etoposide were administered in 11 patients, with the median re-challenge cycle of 3. The overall response rate was 55%. The median PFS and OS from the time of re-challenge treatment were 4 months (95% CI, 2.9–NA) and 9.2 months (95% CI, 8.0–NA), respectively. One patient developed acute exacerbation of ILD 173 days after the last course of re-challenge treatment. Conclusions: Re-challenge chemotherapy can be effective and considered in SCLC patients with pre-existing ILD.
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- 2019
10. Remission of long-standing livedoid vasculopathy using a whole foods plant-based diet with symptoms recurrent on re-challenge with standard Western diet
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Bruce Duncan, Patrick C McHugh, Morgen Smith, and Nicholas A. Wright
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medicine.medical_specialty ,Biopsy ,Case Report ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Western diet ,medicine ,Humans ,Re challenge ,Vascular Diseases ,030212 general & internal medicine ,Symptom onset ,skin and connective tissue diseases ,Adverse effect ,Livedo Reticularis ,medicine.diagnostic_test ,business.industry ,Diet, Vegetarian ,Plant based ,General Medicine ,Middle Aged ,Diet, Western ,Community setting ,Female ,Whole food ,business - Abstract
A 63-year-old woman presented with ulcerations of both lower legs. Symptom onset was 2006. In 2013 she saw a dermatologist and a biopsy suggested livedoid vasculopathy. In 2016 a whole food plant-based diet (WFPB) was advised as a potential treatment in the community setting. The patient changed her diet accordingly, but was not otherwise treated. The symptoms remitted completely with close adherence to the WFPB diet and recurred on multiple occasions associated with poor dietary adherence. There was a self-identified dose–response relationship with degree of adherence and number and intensity of flares. There were no known adverse side effects from the diet change, although the patient felt adherence to be difficult at times. The mechanism is not completely clear; we speculate that the dietary changes directly affect vascular endothelial health, which in turn affects propensity towards a prothrombotic state. More research is needed to elucidate potential mechanisms.
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- 2021
11. Ipilimumab challenge/re-challenge in metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors treated with cabozantinib+nivolumab (CaboNivo) or cabozantinib+nivolumab+ipilimumab (CaboNivoIpi)
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Olena Sierra Ortiz, Scot Anthony Niglio, Howard Streicher, Seth M. Steinberg, Daniel Girardi, Rene Costello, Amir Mortazavi, Sumanta K. Pal, Carlos Diaz, Mohammadhadi Bagheri, John Wright, Lisa M. Cordes, Donald P. Bottaro, P. N. Lara, Biren Saraiya, Lisa Ley, Yang-Min Ning, Jacqueline Cadena, Howard L. Parnes, and Andrea B. Apolo
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Oncology ,Cancer Research ,medicine.medical_specialty ,Metastatic Urothelial Carcinoma ,Cabozantinib ,Genitourinary system ,business.industry ,Ipilimumab ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Re challenge ,Nivolumab ,business ,030215 immunology ,medicine.drug - Abstract
5039 Background: We investigated challenging/re-challenging pts with ipilimumab (ipi) after progression on CaboNivo or CaboNivoIpi. Methods: In a phase I expansion study, patients with mUC post-platinum chemotherapy and other GU tumors patients who progressed on Cabo 40 mg daily plus nivolumab, 3 mg/kg every 21 days (CaboNivo) alone or with ipi, 1 mg/kg every 21 days for 4 cycles (CaboNivoIpi)-and achieved a PR or SD≥6 mo, were challenged/re-challenged with ipi, 1 mg/kg every 21 days for up to 4 cycles. Restaging scans were done every 6 wks for the first 12 wks, then every 8 wks and evaluated by RECIST 1.1. Results: In total, 24 patients were evaluated: 18 pts (8 UC (5 bladder and 3 upper tract), 4 clear cell renal cell carcinoma (RCC), 3 urachal adenocarcinoma (adeno), 2 bladder adeno, and 1 sarcomatoid clear cell RCC) who progressed on CaboNivo were challenged with ipi. In the challenge group, median (m) follow-up was 21.2 months. One pt achieved a PR in the LNs, but was found to have brain metastases before the next restaging, 13 had SD and 4 had PD. Median duration of PR or SD was 3.6 months (95% CI: 1.4 – 7.8 months). The mOS from start of ipi challenge was 13.9 months (95% CI: 5.8 months- not estimable); mPFS was 4.6 months (95% CI: 1.9 – 8.7 months). Grade 1/2 treatment related adverse events (AEs) occurred in all 18 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 11 pts (61%). The most common G≥3 AEs were hypophosphatemia (22%), hypertension (6%), adrenal insufficiency (6%), increased AST (6%), and ALT (6%). Six patients (3 bladder UC, 1 penile squamous cell (SCC) carcinoma, 1 urethral SCC, and 1 clear cell RCC with sarcomatoid features) who progressed on CaboNivoIpi were re-challenged with Ipi. On re-challenge, mfollow-up was 20.9 months. There were no PRs, 3 SDs and 3 PDs. mOS from start of re-challenge was 4.0 months (95% CI: 2.2 – 23.3 months) and mPFS was 1.9 months (95% CI: 1.1 – 2.6 months). Grade 1/2 treatment related AEs occurred in all 6 pts (100%) and ≥Grade 3 (G≥3) AEs occurred in 2pts (33%). G≥3 AEs included 1 hypertension (17%) and 1 hyperphosphatemia (17%). Conclusions: Ipi challenge/re-challenge showed low response rates in pts previously treated with CaboNivo or CaboNivoIpi. However, pts treated with CaboNivo who were challenged with ipi had a better OS than patients who had progressed on CaboNivoIpi and were re-challenged with ipi. Larger trials are warranted testing the ipi challenge in pts progressing on CaboNivo. Clinical trial information: NCT02496208 .
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- 2020
12. Immune checkpoint inhibitor re-challenge in patients with advanced non-small cell lung cancer
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Makoto Ogata, Takayasu Kurata, Kayoko Kibata, Aya Nakaya, Shosaku Nomura, Maiko Niki, Hiroshige Yoshioka, and Toshihiko Kaneda
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Immune checkpoint inhibitors ,immune checkpoint inhibitor ,Pembrolizumab ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,In patient ,Re challenge ,Lung cancer ,Adverse effect ,non-small cell lung cancer ,nivolumab ,business.industry ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Non small cell ,pembrolizumab ,Nivolumab ,business ,re-challenge ,Research Paper - Abstract
// Maiko Niki 1 , Aya Nakaya 1 , Takayasu Kurata 1 , Hiroshige Yoshioka 1 , Toshihiko Kaneda 1 , Kayoko Kibata 1 , Makoto Ogata 1 and Shosaku Nomura 1 1 First Department of Internal Medicine, Kansai Medical University, Shin-machi, Hirakata, Osaka 573-1010, Japan Correspondence to: Aya Nakaya, email: nakaya1016@yahoo.co.jp Keywords: immune checkpoint inhibitor; nivolumab; pembrolizumab; re-challenge; non-small cell lung cancer Received: June 11, 2018 Accepted: July 21, 2018 Published: August 17, 2018 ABSTRACT Background: Immune checkpoint inhibitors have dramatically changed lung cancer treatment, demonstrating an overall survival benefit. There are limited data about re-challenge in patients with non-small cell lung cancer. We attempted to address this question for re-challenge of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer. Methods: We retrospectively analyzed 11 patients with advanced non-small cell lung cancer treated with nivolumab and re-challenged with nivolumab/pemblorizumab at Kansai Medical University Hospital from December 2015 to December 2017. Results: Three patients achieved PR and two patients were in SD. These patients were apt to be good responders to the initial treatment, to develop immune-related adverse events and to be immediately started on re-challenge with immune checkpoint inhibitor. The median PFS was 2.7 (range, 0.5–16.1) months. Five patients (45%) had mild to moderate immune-related adverse events. Conclusion: Our study shows the effectiveness of re-challenge of immune checkpoint inhibitors in a subset of non-small cell lung cancer patients. Re-challenge might become one of treatment option for advanced non-small cell lung cancer.
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- 2018
13. Successful clozapine re-challenge following myocarditis
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Rohan Dhillon, Prashant Tibrewal, Bang Nguyen, Tarun Bastiampillai, and Charles Du
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medicine.medical_specialty ,Myocarditis ,business.industry ,medicine.disease ,030227 psychiatry ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,Medicine ,Humans ,Re challenge ,business ,Intensive care medicine ,Clozapine ,030217 neurology & neurosurgery ,medicine.drug ,Antipsychotic Agents - Abstract
Objective: To explore the evidence around clozapine re-challenge following myocarditis. Conclusion: This case adds to the 17 cases of clozapine re-challenge following myocarditis, of which 71% were successful (12 cases). This demonstrates that re-challenge could be performed safely and effectively in the context of clozapine-induced myocarditis, if accompanied by a strict and rigorous monitoring protocol.
- Published
- 2017
14. Trecc: Re-challenge therapy with anti-EGFR in metastatic colorectal adenocarcinoma (mCRC)
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Celso Lopes Mello, Tiago Felismino, Mariana Petaccia de Macedo, Larissa Machado, Amanda Karani, Diogo De Brito Sales, and Lara Azevedo Diniz
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Disease progression ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Overall survival ,Medicine ,Colorectal adenocarcinoma ,Re challenge ,business ,030215 immunology - Abstract
683 Background: Anti-EGFR plus chemotherapy (CT) promotes high response rates (RR) and median overall survival (OS) surpasses 30 months in RASwt/BRAFwt mCRC. After disease progression (PD), resistance mechanisms have been described. The aim of our study was to evaluate efficacy of anti-EGFR re-challenge (TRECC). Methods: We retrospectively analyzed a cohort of patients (pts) with mCRC. All pts had received anti-EGFR plus CT and were discontinued for different reasons. During the treatment, there was re-challenge with an anti-EGFR + CT. We aimed to evaluate progression-free survival (PFS) and OS after re-challenge and prognostic factors associated with PFS. Results: Sixty eight pts met the study criteria. Median follow-up after re-challenge was 39.3m. Discontinuation after first exposure was 25% due to PD; 75% for other reasons. Median anti-EGFR free interval was 10.5m. At re-challenge, main CT regime was: FOLFIRI 58.8%, Cetuximab and Panitumumab were used in 59 and 9 pts respectively. mPFS after re-challenge was 6.6m; mOS was 24.4m. Objective response rate (CR + PR) at re-challenge was 42.6%. In an univariate analysis, adverse prognostic factors related to PFS were: absence of objective response at 1st EGFR exposure (HR 2.12, CI:1.20-3.74 p = 0.009); PD as reason for 1st discontinuation (HR 3.44, CI:1.88-6.29 p < 0.0001); re-challenge at fourth or later lines (HR 2,51, CI:1.49-4.23 p = 0.001); panitumumab use (HR 2.26 CI:1.18-5.54 p = 0.017). In a multivariate model, only PD as reason for 1st discontinuation remained statistically significant (HR = 2.63, CI:1.14-6.03 p = 0.022). mPFS was 3.3m and 8.4m and mOS was 7,5m and 33,4m in patients with PD as reason for 1st discontinuation and other reasons respectively. Conclusions: Re-challenge therapy is commonly used due to paucity of effective lines of treament for mCRC. In our analysis, pts that stopped 1st anti-EGFR therapy due to PD have shorter survival, suggesting these pts do not benefit from TRECC. However, interruption due to treatment holiday after PR/CR resulted in longer PFS. In conclusion, for a selected group of pts, TRECC could be considered a strategy of treatment. Due to the limited number of pts, our data should be evaluated in a prospective cohort of patients.
- Published
- 2019
15. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia
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Sukhwinder S. Shergill, John Lally, Victoria Bell, and Jessica J. Foster
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medicine.medical_specialty ,Psychosis ,business.industry ,Declaration ,Short Report ,Schizoaffective disorder ,Creative commons ,Neutropenia ,medicine.disease ,Dyscrasia ,030227 psychiatry ,3. Good health ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,medicine ,Re challenge ,Psychiatry ,business ,030217 neurology & neurosurgery ,Clozapine ,medicine.drug - Abstract
A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
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- 2016
16. Successful re-challenge with anti-BRAF and anti-MEK in a patient with symptomatic melanoma flare
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Caroline Robert, Tony Ibrahim, Amadine Weill, Emilie Routier, and Maria Baz
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Melanoma ,medicine.disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Re challenge ,030212 general & internal medicine ,business ,Flare - Published
- 2017
17. Investigating Systemic Immunity to Typhoid and Paratyphoid Fever: Characterising the Response to Re-challenge in a Controlled Human Infection Model
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Celina Jin, Brian Angus, Alison Simmons, Melita A. Gordon, Andrew J. Pollard, Malick M. Gibani, Vincenzo Cerundolo, Helena Thomaides-Brears, Sonu Shrestha, Giorgio Napolitani, and Lorena Precaido-Llanes
- Subjects
business.industry ,030231 tropical medicine ,Attack rate ,Paratyphoid fever ,Systemic immunity ,medicine.disease ,Virology ,Typhoid fever ,03 medical and health sciences ,0302 clinical medicine ,Infectious Diseases ,Oncology ,Immunity ,medicine ,Re challenge ,030212 general & internal medicine ,business - Published
- 2017
18. QUADRUPLE THREAT: A phase II trial of RRx-001 followed by etoposide-platinum re-challenge in previously treated small cell lung cancer
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Christina Brzezniak, Daniel Morgensztern, Alexander I. Spira, Bryan Oronsky, Heather A. Wakelee, Sukhmani K. Padda, Saiama N. Waqar, Thomas J. Reid, Karen Zeman, Michal G. Rose, Ellice Yuen-Ming Wong, Nacer Abrouk, and Patrick C. Ma
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0301 basic medicine ,Drug ,Cancer Research ,business.industry ,media_common.quotation_subject ,chemistry.chemical_element ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,chemistry ,Cancer stem cell ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Re challenge ,Non small cell ,Previously treated ,business ,Platinum ,Etoposide ,medicine.drug ,media_common ,Chemotherapy resistance - Abstract
e20575Background: RRx-001 is a first-in-class epi-immunotherapeutic drug that targets tumor-associated macrophages and cancer stem cells to reverse chemotherapy resistance in small cell lung cancer...
- Published
- 2018
19. A severe hypersensitivity reaction to abacavir following re-challenge
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Sej Todd and Carol Emerson
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Anti-HIV Agents ,Pyridones ,Human immunodeficiency virus (HIV) ,HIV Infections ,02 engineering and technology ,Dermatology ,medicine.disease_cause ,Piperazines ,Drug Hypersensitivity ,03 medical and health sciences ,020210 optoelectronics & photonics ,0302 clinical medicine ,Abacavir ,Oxazines ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,Humans ,Pharmacology (medical) ,Re challenge ,030212 general & internal medicine ,business.industry ,Public Health, Environmental and Occupational Health ,virus diseases ,Dideoxynucleosides ,Hypersensitivity reaction ,Drug Combinations ,Infectious Diseases ,HLA-B Antigens ,Lamivudine ,Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination ,Immunology ,HIV-1 ,business ,Heterocyclic Compounds, 3-Ring ,medicine.drug - Abstract
We report this case to highlight the possibility of a severe hypersensitivity reaction as an important potential consequence of couples, living with HIV, sharing anti-retroviral treatment. An HIV-1 positive and carrier of HLA-B*57:01 allele, treatment experienced man was commenced one pill Regimen Stribild (tenofovir, emtricitabine, elvitegravir and cobicistat) in July 2015. On running short of medication, he admitted to sharing his partner’s treatment (Triumeq; abacavir, lamivudine and dolutegravir). On the second occasion, re-introduction resulted in whole body rash 4 h post dose and was associated with fever, respiratory symptoms, headache and vomiting. On examination, he was pyrexic, tachyponeic, tachycardiac and hypotensive. Hypersensitivity to abacavir can cause significant morbidity. Re-challenge can result in a more rapid, severe and potentially life-threatening reaction. This potentially could become an increasing problem with more couples, living with HIV, sharing medication.
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- 2016
20. Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study
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Meghan J. Mooradian, John J. Park, Dirk Schadendorf, Francesco De Rosa, Ana Arance, Sara Valpione, Grant A. McArthur, Keith T. Flaherty, Axel Hauschild, Elisabeth Livingstone, Matteo S. Carlino, Wen Xu, Paolo A. Ascierto, Michele Maio, Joanna Mangana, James Larkin, Georgina V. Long, Simone M. Goldinger, Michael Weichenthal, and Paul Lorigan
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,Surgery ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Acquired resistance ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Re challenge ,business - Abstract
9512 Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1st BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases.
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- 2017
21. Second TKI Discontinuation in CML Patients That Failed First Discontinuation and Subsequently Regained Deep Molecular Response after TKI Re-Challenge
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Stéphane Giraudier, Stephane Morisset, Franck E. Nicolini, Agnès Guerci-Bresler, Philippe Rousselot, Martine Escoffre, Bruno Varet, Gabriel Etienne, Françoise Huguet, Laurence Legros, Thomas Pagliardini, and Francois-Xavier Mahon
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medicine.medical_specialty ,business.industry ,Immunology ,Imatinib ,Cell Biology ,Hematology ,Biochemistry ,Discontinuation ,Dasatinib ,03 medical and health sciences ,0302 clinical medicine ,Nilotinib ,030220 oncology & carcinogenesis ,Internal medicine ,Cohort ,medicine ,Re challenge ,business ,Survival rate ,Accelerated phase ,030215 immunology ,medicine.drug - Abstract
Background: Tyrosine kinase inhibitors (TKIs) are able to induce, in some chronic myeloid leukemia (CML) patients, long-term undetectable molecular disease (UMD). Several studies have now demonstrated that TKIs could be safely discontinued in those patients previously treated with imatinib (STIM, TWISTER, EUROSKI) and more recently with nilotinib and dasatinib (STOP 2G-TKI). All these studies show a Treatment-Free Remission (TFR) rate reaching ~50%. However, a major issue needs to be resolved for the ~50% of patients that fail such TFR strategies. Methods: We have previously reported the possibility of a second imatinib discontinuation in 16 patients who obtained a second UMD state according to the STIM criteria (RE-STIM observational study, Legros et al. Blood 2012). Here, we report a larger cohort of patients who attempt twice TKI-discontinuations with enlarged inclusion criteria: Adults CML patients without prior allogeneic transplantation or progression to advanced phase CML undergoing a 2nd attempt of TKI discontinuation for sustained deep molecular response after a 1st failure. All patients were followed in CML reference centers and according to the EUTOS-ELN accreditation criteria for BCR-ABL assessments with minimal numbers of 32,000 ABL copies/sample. Results: At the time of analysis (1st July 2016), 67 patients (median age: 51 years (range: 25-80 years)) were included. At CML diagnosis, 64 patients were in chronic phase (CP) and 3 patients in accelerated phase (AP). The Sokal risk and the EUTOS long-term survival scores (ELTS) were respectively low in 47% and 68%, intermediate in 36% and 16%, high in 11% and 2% and unknown in 6% and 14% of patients. All patients were treated initially with imatinib and 16% of patients switch to nilotinib (6/11) or to dasatinib (5/11) for intolerance/resistance reasons prior to the 1st TKI discontinuation. The median time on TKI prior to the 1st discontinuation was 63 months (range: 30-146) and the median duration of 1st CMR was 35 months (range: 20-85). The 1st molecular relapse occurred with a median of 2.5 months (range: 0-22) and the second UMD after TKI re-challenge was obtained with a median of 4.4 months (0-40). The reason of the TKI re-challenge was loss of UMD in 43%, loss of MMR in 55% and unknown in 1%. The TKI re-challenge (imatinib 73%, nilotinib 16%, dasatinib 11%) was then administered during a median of 31 months (range: 9-72 months) before the 2nd attempt of discontinuation. At 2nd TKI cessation, 85% of patients were in UMD, 3% in MR4.5, 6 % in MR4, 3% in MMR and 3% unknown. Thirty out of sixty-eight (44%) patients remained treatment-free after a median follow-up of 21.5 months (1-106), see figure. Similarly to 1st attempts, the majority of loss of MMR occurred during the first 6-12 months in this 2nd attempt cohort. Gender, age, disease phase, prognosis scores, prior interferon exposure, initial TKI type, and duration of UMD were not found to have any impact on the outcome after the 2nd attempt in a multivariate analysis. In contrast, a longer time to obtain the first UMD before the 1st attempt was associated with a significantly lower molecular disease-free survival rate after the 2nd discontinuation (p = 0.048). All patients are alive at last follow-up except one who died from an unrelated CML reason (heart attack under imatinib). Conclusion: TKIs could safely and successfully be discontinued a second time in CML pts despite a 1st failure. Figure. Figure. Disclosures Nicolini: BMS: Consultancy, Honoraria; Ariad pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Etienne:BMS: Speakers Bureau; Pfizer: Speakers Bureau; ARIAD: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Huguet:Pfizer, Novartis, BMS, Ariad, Jazz, Amgen: Membership on an entity's Board of Directors or advisory committees. Guerci-Bresler:Pfizer: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; ARIAD: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Mahon:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ARIAD: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria.
- Published
- 2016
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