{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:42:22Z","timestamp":1790080942666,"version":"4.0.1"},"reference-count":25,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>PI3 kinase (PI3K) activity is critical for survival of neoplastic B cells in patients with chronic lymphocytic leukemia (CLL). Blockade of PI3K signaling with idelalisib is effective for the treatment of relapsed CLL in combination with the anti-CD20 antibody ofatumumab. In this single-arm, open-label, nonrandomized phase 2 study, we investigated the efficacy and safety of idelalisib with ofatumumab in 27 patients with treatment-na\u00efve CLL in need of therapy. Patients were planned to receive idelalisib for 2 monthly cycles, then idelalisib and ofatumumab for 6 cycles, followed by idelalisib indefinitely. The study was closed early and all patients ceased therapy when an increased rate of death as a result of infection was observed on other first-line idelalisib trials. Median time on therapy was 8.1 months, and median duration of follow-up was 39.7 months. We previously reported high rates of hepatotoxicity in a smaller cohort of patients in this trial; toxicities necessitated therapy discontinuation in 15 patients after a median of 7.7 months. The most frequent grade \u22653 adverse events were transaminitis (52% of patients), neutropenia (33%), and colitis\/diarrhea (15%). The best overall response rate (ORR) was 88.9%, including 1 complete response. Median progression-free survival (PFS) was 23 months (95% confidence interval [CI], 18-36 months); 11 patients have not yet required second-line therapy. Idelalisib and ofatumumab demonstrated an unacceptable safety profile in the first-line setting, which resulted in a short PFS despite a high ORR. Future development of PI3K inhibitors for use in treatment-na\u00efve CLL will require novel approaches to mitigate toxicities. This trial was registered at www.clinicaltrials.gov as #NCT02135133.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018030221","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T16:55:36Z","timestamp":1554828936000},"page":"1167-1174","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":26,"title":["Efficacy results of a phase 2 trial of first-line idelalisib plus ofatumumab in chronic lymphocytic leukemia"],"prefix":"10.1182","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6033-3363","authenticated-orcid":false,"given":"Benjamin L.","family":"Lampson","sequence":"first","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haesook T.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Davids","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-9257","authenticated-orcid":false,"given":"Jeremy S.","family":"Abramson","sequence":"additional","affiliation":[{"name":"Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold S.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe A.","family":"Armand","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7251-8082","authenticated-orcid":false,"given":"Robin M.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Boston, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon E.","family":"Arnason","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Beth Israel Deaconess Medical Center, Boston, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Z.","family":"Rassenti","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Kipps","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5441-1516","authenticated-orcid":false,"given":"Joshua","family":"Fein","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey M.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Hanna","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-4961","authenticated-orcid":false,"given":"Jennifer R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"issue":"17","key":"2020021108280118200_B1","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1182\/blood-2017-10-810044","article-title":"Single-agent ibrutinib in treatment-na\u00efve and relapsed\/refractory chronic lymphocytic leukemia: a 5-year experience","volume":"131","author":"O\u2019Brien","year":"2018","journal-title":"Blood"},{"issue":"4","key":"2020021108280118200_B2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1513257","article-title":"Targeting BCL2 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