{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:01:51Z","timestamp":1792710111787,"version":"4.5.0"},"reference-count":8,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) is typically chemoresistant, with a poor prognosis. We hypothesized that the oral Bcl-2 inhibitor venetoclax could sensitize RS to chemoimmunotherapy and improve outcomes. We conducted a single-arm, investigator-sponsored, phase 2 trial of venetoclax plus dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (VR-EPOCH) to determine the rate of complete response (CR). Patients received R-EPOCH for 1 cycle, then after count recovery, accelerated daily venetoclax ramp-up to 400 mg, then VR-EPOCH for up to 5 more 21-day cycles. Responders received venetoclax maintenance or cellular therapy off-study. Twenty-six patients were treated, and 13 of 26 (50%) achieved CR, with 11 achieving undetectable bone marrow minimal residual disease for CLL. Three additional patients achieved partial response (overall response rate, 62%). Median progression-free survival was 10.1 months, and median overall survival was 19.6 months. Hematologic toxicity included grade \u22653 neutropenia (65%) and thrombocytopenia (50%), with febrile neutropenia in 38%. No patients experienced tumor lysis syndrome with daily venetoclax ramp-up. VR-EPOCH is active in RS, with deeper, more durable responses than historical regimens. Toxicities from intensive chemoimmunotherapy and venetoclax were observed. Our data suggest that studies comparing venetoclax with chemoimmunotherapy to chemoimmunotherapy alone are warranted. This trial was registered at www.clinicaltrials.gov as #NCT03054896.<\/jats:p>","DOI":"10.1182\/blood.2021011386","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T16:10:46Z","timestamp":1637165446000},"page":"686-689","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":74,"title":["Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-2003","authenticated-orcid":false,"given":"Matthew S.","family":"Davids","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-7874","authenticated-orcid":false,"given":"Kerry A.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Division of Hematology, The Ohio State University, Columbus, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3119-6507","authenticated-orcid":false,"given":"Svitlana","family":"Tyekucheva","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Pazienza","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Renner","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"Montegaard","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udochukwu","family":"Ihuoma","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy Z.","family":"Lehmberg","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-9769","authenticated-orcid":false,"given":"Erin M.","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-5054","authenticated-orcid":false,"given":"Catherine J.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caron A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-6031","authenticated-orcid":false,"given":"Philip A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; and"}],"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":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"6","key":"2022020316232093300_B1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/bjh.16748","article-title":"Clinical outcome and prognostic factors of patients with Richter syndrome: real-world study of the Spanish Chronic Lymphocytic Leukemia Study Group (GELLC)","volume":"190","author":"Abrisqueta","year":"2020","journal-title":"Br J Haematol."},{"key":"2022020316232093300_B2","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.1200\/JCO.2017.35.15_suppl.7505","article-title":"Richter\u2019s syndrome (RS) in patients with chronic lymphocytic leukemia (CLL) on novel agent therapy","volume":"35","author":"Davids","year":"2017","journal-title":"J Clin Oncol."},{"issue":"2","key":"2022020316232093300_B3","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/bjh.15035","article-title":"A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor","volume":"180","author":"Rogers","year":"2018","journal-title":"Br J Haematol."},{"issue":"4","key":"2022020316232093300_B4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1513257","article-title":"Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia","volume":"374","author":"Roberts","year":"2016","journal-title":"N Engl J Med."},{"issue":"8","key":"2022020316232093300_B5","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1200\/JCO.2016.70.4320","article-title":"Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma","volume":"35","author":"Davids","year":"2017","journal-title":"J Clin Oncol."},{"issue":"12","key":"2022020316232093300_B6","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","article-title":"Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines","volume":"111","author":"Hallek","year":"2008","journal-title":"Blood."},{"issue":"22","key":"2022020316232093300_B7","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1200\/JCO.20.00303","article-title":"Multicenter study of risk-adapted therapy with dose-adjusted EPOCH-R in adults with untreated Burkitt lymphoma","volume":"38","author":"Roschewski","year":"2020","journal-title":"J Clin Oncol."},{"issue":"27","key":"2022020316232093300_B8","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J Clin Oncol."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/5\/686\/1866530\/bloodbld2021011386.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/139\/5\/686\/1866530\/bloodbld2021011386.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T11:24:06Z","timestamp":1643887446000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/139\/5\/686\/482662\/Venetoclax-plus-dose-adjusted-R-EPOCH-for-Richter"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":8,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,2,3]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2021011386","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]}}}