Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia
| Autor: | John C. Byrd, Raquel Izumi, Min Hui Wang, David M. Weiss, Cheng Quah, Veerendra Munugalavadla, Seema A. Bhat, Michael Gulrajani, Melanie M. Frigault, James S. Blachly, Gerard Lozanski, Mojgan Jianfar, Kerry A. Rogers, Barbara L. Andersen, Jennifer A. Woyach, Ahmed Hamdy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Adult Male medicine.medical_specialty Chronic lymphocytic leukemia Antibodies Monoclonal Humanized Article Drug Administration Schedule 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Refractory Obinutuzumab immune system diseases Internal medicine hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols medicine Agammaglobulinaemia Tyrosine Kinase Bruton's tyrosine kinase Humans Aged Cell Proliferation biology business.industry Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell 030104 developmental biology Treatment Outcome chemistry 030220 oncology & carcinogenesis Ibrutinib Pyrazines Benzamides biology.protein Acalabrutinib Interleukin-2 Rituximab Female Refractory Chronic Lymphocytic Leukemia business medicine.drug |
| Zdroj: | Cancer Discov |
| ISSN: | 0229-6918 |
| Popis: | Acalabrutinib is a selective irreversible Bruton tyrosine kinase (BTK) inhibitor that does not affect IL2-associated tyrosine kinase or antibody-dependent cellular cytotoxicity, making it an attractive candidate for combination therapy with anti-CD20 antibodies. We investigated acalabrutinib plus obinutuzumab in a phase Ib/II study (NCT02296918) of patients with treatment-naïve or relapsed/refractory chronic lymphocytic leukemia (CLL). Nineteen treatment-naïve and 26 relapsed/refractory patients were treated with acalabrutinib (100 mg twice daily) until progression and obinutuzumab (cycle 1: 100 mg day 1, 900 mg day 2, 1000 mg days 8 and 15; cycles 2–6: 1,000 mg day 1). Grade 3/4 adverse events occurred in 71% of patients. Overall response rates were 95% (treatment-naïve) and 92% (relapsed/refractory). Thirty-two percent of treatment-naïve and 8% of relapsed/refractory patients achieved complete remission. At 36 months, 94% (treatment-naïve) and 88% (relapsed/refractory) were progression free. Acalabrutinib plus obinutuzumab was well tolerated, producing high and durable responses in treatment-naïve and relapsed/refractory CLL. Significance: Rituximab plus the less selective BTK inhibitor ibrutinib has not shown benefit in CLL; however, the selective BTK inhibitor acalabrutinib plus the antibody-dependent cellular cytotoxicity–enhanced antibody obinutuzumab yielded durable responses that deepened over time in treatment-naïve and relapsed/refractory CLL, supporting the evaluation of this approach in larger, comparative studies in CLL. This article is highlighted in the In This Issue feature, p. 327 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|