{"doi":"10.1111/bjh.19419","title":"Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas","abstract":"The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.","journal":"British Journal of Haematology","year":2024,"id":463808,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":262216,"name":"Catherine Diefenbach","orcid":"0000-0003-1116-3246","position":1,"is_corresponding":false},{"id":258327,"name":"Deepa Jagadeesh","orcid":"0000-0002-1772-0659","position":2,"is_corresponding":false},{"id":1294540,"name":"Adam Asch","orcid":null,"position":3,"is_corresponding":false},{"id":1294161,"name":"Abhijeet Kumar","orcid":"0000-0002-6990-4775","position":4,"is_corresponding":false},{"id":1294541,"name":"Michaela L. Tsai","orcid":null,"position":5,"is_corresponding":false},{"id":1294162,"name":"Thomas Jandl","orcid":"0000-0002-9481-4229","position":6,"is_corresponding":false},{"id":35668,"name":"Izidore S. Lossos","orcid":"0000-0002-9346-9013","position":7,"is_corresponding":false},{"id":504914,"name":"Vaishalee P. Kenkre","orcid":"0009-0000-4539-9332","position":8,"is_corresponding":false},{"id":278931,"name":"Farrukh T. Awan","orcid":"0000-0003-1813-9812","position":9,"is_corresponding":false},{"id":44874,"name":"William Novotny","orcid":null,"position":10,"is_corresponding":false},{"id":1294163,"name":"Jane Huang","orcid":"0009-0004-4549-6625","position":11,"is_corresponding":false},{"id":1294164,"name":"Miao Lü","orcid":"0000-0003-3058-9461","position":12,"is_corresponding":false},{"id":1254727,"name":"Prabhu Rajagopalan","orcid":"0000-0003-2615-8458","position":13,"is_corresponding":false},{"id":1254728,"name":"Richard Ghalie","orcid":"0000-0001-6882-8179","position":14,"is_corresponding":false},{"id":233551,"name":"Andrew D. Zelenetz","orcid":"0000-0003-1403-6883","position":15,"is_corresponding":false},{"id":232465,"name":"Jacob D. Soumerai","orcid":"0000-0002-3062-6819","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T02:04:33.257852Z","pmid":"38500476","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":[]}