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Start Over Author "Graef, Thorsten" Topic hematologic neoplasms
3 results on '"Graef, Thorsten"'

1. Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

Author

Brown, Jennifer R, Moslehi, Javid, Ewer, Michael S, O'Brien, Susan M, Ghia, Paolo, Cymbalista, Florence, Shanafelt, Tait D, Fraser, Graeme, Rule, Simon, Coutre, Steven E, Dilhuydy, Marie‐Sarah, Cramer, Paula, Jaeger, Ulrich, Dreyling, Martin, Byrd, John C, Treon, Steven, Liu, Emily Y, Chang, Stephen, Bista, Amulya, Vempati, Rama, Boornazian, Lisa, Valentino, Rudolph, Reddy, Vijay, Mahler, Michelle, Yang, Huiying, Graef, Thorsten, and Burger, Jan A

Subjects
Cancer, Clinical Research, Clinical Trials and Supportive Activities, Hematology, Rare Diseases, Good Health and Well Being, Adenine, Aged, Female, Hematologic Neoplasms, Hemorrhage, Humans, Incidence, Male, Middle Aged, Piperidines, Pyrazoles, Pyrimidines, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, B-cell neoplasms, lymphoid leukaemias, signalling therapies, clinical results in lymphomas, Cardiorespiratory Medicine and Haematology, Immunology
Abstract

Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.

Published
2019

2. Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma.

Author

Chari, Ajai, Larson, Sarah, Holkova, Beata, Cornell, Robert F., Gasparetto, Cristina, Karanes, Chatchada, Matous, Jeffrey V., Niesvizky, Ruben, Valent, Jason, Lunning, Matthew, Usmani, Saad Z., Anderson, Larry D., Chang, Lipo, Lee, Yihua, Pak, Yvonne, Salman, Zeena, Graef, Thorsten, Bilotti, Elizabeth, and Chhabra, Saurabh

Subjects
IBRUTINIB, PROTEASOME inhibitors, HEMATOLOGIC malignancies, CANCER relapse, MULTIPLE myeloma
Abstract

This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia. Overall response rate was 67% (very good partial response, 21%; stringent complete response, 2%), with an additional 9% minimal response. Median progression-free survival was 7.2 months and was not inferior in refractory nor high-risk patients. Median overall survival was not reached. Ibrutinib plus carfilzomib demonstrated encouraging responses with a manageable safety profile in this advanced population. [ABSTRACT FROM AUTHOR]

Published
2018
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3. Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis

Author

Javid Moslehi, Simon Rule, Martin Dreyling, Susan O'Brien, Amulya Bista, Rudolph Valentino, Stephen Chang, Steven Coutre, Michelle Mahler, Thorsten Graef, Huiying Yang, Marie Sarah Dilhuydy, Rama Vempati, Paolo Ghia, Paula Cramer, John C. Byrd, Michael S. Ewer, Florence Cymbalista, Steven P. Treon, Jennifer R. Brown, Graeme Fraser, Emily Y. Liu, Ulrich Jaeger, Jan A. Burger, Vijay Reddy, Tait D. Shanafelt, Lisa Boornazian, Brown, Jennifer R., Moslehi, Javid, Ewer, Michael S., O'Brien, Susan M., Ghia, Paolo, Cymbalista, Florence, Shanafelt, Tait D., Fraser, Graeme, Rule, Simon, Coutre, Steven E., Dilhuydy, Marie-Sarah, Cramer, Paula, Jaeger, Ulrich, Dreyling, Martin, Byrd, John C., Treon, Steven, Liu, Emily Y., Chang, Stephen, Bista, Amulya, Vempati, Rama, Boornazian, Lisa, Valentino, Rudolph, Reddy, Vijay, Mahler, Michelle, Yang, Huiying, Graef, Thorsten, and Burger, Jan A.

Subjects
Male, Time Factors, clinical results in lymphomas, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, B-cell neoplasm, Piperidines, law, Risk Factors, B‐cell neoplasms, signalling therapie, Randomized Controlled Trials as Topic, education.field_of_study, biology, Haematological Malignancy, Incidence (epidemiology), Incidence, Hematology, Middle Aged, lymphoid leukaemia, 030220 oncology & carcinogenesis, Ibrutinib, Hematologic Neoplasms, Female, Research Paper, medicine.medical_specialty, clinical results in lymphoma, Population, Hemorrhage, 03 medical and health sciences, Internal medicine, medicine, Bruton's tyrosine kinase, Humans, education, Aged, business.industry, Adenine, Confidence interval, lymphoid leukaemias, Discontinuation, Pyrimidines, chemistry, Relative risk, biology.protein, Pyrazoles, business, signalling therapies, 030215 immunology
Abstract

Summary Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B‐cell malignancies. In ibrutinib clinical studies, low‐grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any‐grade bleeding were similar for single‐agent ibrutinib and ibrutinib combinations (39% and 40%). Low‐grade bleeding was more common in ibrutinib‐treated than comparator‐treated patients (35% and 15%), and early low‐grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person‐months). MH led to treatment discontinuation in 1% of all ibrutinib‐treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure‐adjusted relative risk for MH in both the total ibrutinib‐treated population (1.9; 95% confidence interval, 1.2–3.0) and RCT comparator‐treated patients (2.4; 95% confidence interval, 1.0–5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B‐cell malignancies.

Published
2018

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