{"doi":"10.1158/2159-8290.cd-19-1130","title":"Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia","abstract":"Abstract 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","journal":"Cancer Discovery","year":2020,"id":57238,"datarank":3.091421824799515,"base_score":4.382026634673881,"endowment":4.382026634673881,"self_citation_contribution":0.6573039952010823,"citation_network_contribution":2.4341178295984327,"self_endowment_contribution":0.6573039952010823,"citer_contribution":2.4341178295984327,"corpus_percentile":null,"corpus_rank":null,"citation_count":79,"citer_count":66,"citers_with_citation_signal":60,"citers_with_endowment":60,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02296918"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295288,"name":"James S. Blachly","orcid":"0000-0002-4275-5562","position":1,"is_corresponding":false},{"id":278927,"name":"Kerry A. Rogers","orcid":"0000-0001-5748-7874","position":2,"is_corresponding":false},{"id":278932,"name":"Seema A. Bhat","orcid":"0000-0001-7844-0856","position":3,"is_corresponding":false},{"id":300225,"name":"Mojgan Jianfar","orcid":null,"position":4,"is_corresponding":false},{"id":278008,"name":"Gerard Lozanski","orcid":"0000-0002-5095-0456","position":5,"is_corresponding":false},{"id":278935,"name":"David M. Weiss","orcid":"0000-0001-5806-4144","position":6,"is_corresponding":false},{"id":278930,"name":"Barbara L. Andersen","orcid":"0000-0002-7335-1325","position":7,"is_corresponding":false},{"id":280054,"name":"Michael Gulrajani","orcid":null,"position":8,"is_corresponding":false},{"id":298603,"name":"Melanie M. Frigault","orcid":"0009-0002-8525-4239","position":9,"is_corresponding":false},{"id":278263,"name":"Ahmed Hamdy","orcid":"0009-0008-7188-4188","position":10,"is_corresponding":false},{"id":278262,"name":"Raquel Izumi","orcid":"0000-0002-0895-2597","position":11,"is_corresponding":false},{"id":298604,"name":"Veerendra Munugalavadla","orcid":"0000-0002-2390-3822","position":12,"is_corresponding":false},{"id":298605,"name":"Cheng S. Quah","orcid":"0009-0000-4250-7828","position":13,"is_corresponding":false},{"id":298606,"name":"Minhui Wang","orcid":"0000-0001-8121-7786","position":14,"is_corresponding":false},{"id":35686,"name":"John C. Byrd","orcid":"0000-0001-9830-0711","position":15,"is_corresponding":false},{"id":245731,"name":"Jennifer A. Woyach","orcid":"0000-0002-3403-9144","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T21:06:31.136481Z","pmid":"31915195","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}