{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:59:13Z","timestamp":1793386753897,"version":"4.5.0"},"reference-count":88,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:sec id=\"ab-jrv230004-1\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Chronic lymphocytic leukemia (CLL), defined by a minimum of 5\u2009\u00d7\u200910\n                      <jats:sup>9<\/jats:sup>\n                      \/L monoclonal B cells in the blood, affects more than 200\u202f000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv230004-2\">\n                    <jats:title>Observations<\/jats:title>\n                    <jats:p>At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and\/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia\/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3\u2032-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-jrv230004-3\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>More than 200\u202f000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2023.1946","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T11:05:09Z","timestamp":1679396709000},"page":"918","source":"Crossref","is-referenced-by-count":248,"title":["Diagnosis and Treatment of Chronic Lymphocytic Leukemia"],"prefix":"10.1001","volume":"329","author":[{"given":"Mazyar","family":"Shadman","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington"},{"name":"Medical Oncology Division, University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"jrv230004r2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.v72.1","article-title":"Cancer statistics, 2022.","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"issue":"21","key":"jrv230004r3","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1182\/blood.2019003453","article-title":"International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia.","volume":"135","author":"Condoluci","year":"2020","journal-title":"Blood"},{"issue":"5","key":"jrv230004r4","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1111\/ejh.v108.5","article-title":"Identifying patients with chronic lymphocytic leukemia without need of treatment: end of endless watch and wait?","volume":"108","author":"Brieghel","year":"2022","journal-title":"Eur J Haematol"},{"issue":"7","key":"jrv230004r5","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms.","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"jrv230004r6","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1146\/pathmechdis.2014.9.issue-1","article-title":"The pathogenesis of chronic lymphocytic leukemia.","volume":"9","author":"Zhang","year":"2014","journal-title":"Annu Rev Pathol"},{"issue":"5","key":"jrv230004r7","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1056\/NEJMra1908213","article-title":"Treatment of chronic lymphocytic leukemia.","volume":"383","author":"Burger","year":"2020","journal-title":"N Engl J Med"},{"issue":"7","key":"jrv230004r8","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s00277-012-1460-z","article-title":"Immunological aspects in chronic lymphocytic leukemia (CLL) development.","volume":"91","author":"Garc\u00eda-Mu\u00f1oz","year":"2012","journal-title":"Ann Hematol"},{"issue":"9","key":"jrv230004r9","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.3324\/haematol.2019.236000","article-title":"Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies.","volume":"105","author":"Delgado","year":"2020","journal-title":"Haematologica"},{"issue":"11","key":"jrv230004r10","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/s41571-019-0239-8","article-title":"Chronic lymphocytic leukaemia: from genetics to treatment.","volume":"16","author":"Bosch","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"issue":"12","key":"jrv230004r11","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1002\/ajh.v92.12","article-title":"IGHV mutational status testing in chronic lymphocytic leukemia.","volume":"92","author":"Crombie","year":"2017","journal-title":"Am J Hematol"},{"issue":"1","key":"jrv230004r12","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000811","article-title":"COVID-19 vaccination response and its practical application in patients with chronic lymphocytic leukemia.","volume":"7","author":"Shadman","year":"2022","journal-title":"Hemasphere"},{"issue":"10","key":"jrv230004r13","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1182\/blood-2009-04-214346","article-title":"Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the Hospital Clinic of Barcelona experience.","volume":"114","author":"Abrisqueta","year":"2009","journal-title":"Blood"},{"issue":"21","key":"jrv230004r14","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1001\/jama.2014.14553","article-title":"Chronic lymphocytic leukemia: a clinical review.","volume":"312","author":"Nabhan","year":"2014","journal-title":"JAMA"},{"issue":"2","key":"jrv230004r15","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1182\/blood.V46.2.219.219","article-title":"Clinical staging of chronic lymphocytic leukemia.","volume":"46","author":"Rai","year":"1975","journal-title":"Blood"},{"issue":"25","key":"jrv230004r16","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"issue":"6","key":"jrv230004r17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.6004\/jnccn.2022.0031","article-title":"NCCN Guidelines Insights: chronic lymphocytic leukemia\/small lymphocytic lymphoma, version 3.2022.","volume":"20","author":"Wierda","year":"2022","journal-title":"J Natl Compr Canc Netw"},{"issue":"25","key":"jrv230004r18","doi-asserted-by":"crossref","first-page":"6618","DOI":"10.1182\/blood-2011-05-357251","article-title":"General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL.","volume":"118","author":"Fazi","year":"2011","journal-title":"Blood"},{"issue":"2","key":"jrv230004r19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1182\/blood.2020009813","article-title":"The CLL International Prognostic Index predicts outcomes in monoclonal B-cell lymphocytosis and Rai 0 CLL.","volume":"138","author":"Parikh","year":"2021","journal-title":"Blood"},{"issue":"1","key":"jrv230004r20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V","article-title":"A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis.","volume":"48","author":"Binet","year":"1981","journal-title":"Cancer"},{"issue":"4","key":"jrv230004r21","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000707","article-title":"Cytogenetics in chronic lymphocytic leukemia: ERIC perspectives and recommendations.","volume":"6","author":"Baliakas","year":"2022","journal-title":"Hemasphere"},{"issue":"26","key":"jrv230004r22","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJM200012283432602","article-title":"Genomic aberrations and survival in chronic lymphocytic leukemia.","volume":"343","author":"D\u00f6hner","year":"2000","journal-title":"N Engl J Med"},{"issue":"18","key":"jrv230004r23","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1182\/blood-2015-05-647578","article-title":"Presence of multiple recurrent mutations confers poor trial outcome of relapsed\/refractory CLL.","volume":"126","author":"Gui\u00e8ze","year":"2015","journal-title":"Blood"},{"issue":"2","key":"jrv230004r24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1182\/blood.2021010845","article-title":"The CLL12 trial: ibrutinib vs placebo in treatment-na\u00efve, early-stage chronic lymphocytic leukemia.","volume":"139","author":"Langerbeins","year":"2022","journal-title":"Blood"},{"issue":"8","key":"jrv230004r25","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1038\/s41375-020-0747-7","article-title":"Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial.","volume":"34","author":"Herling","year":"2020","journal-title":"Leukemia"},{"issue":"6","key":"jrv230004r29","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1158\/2643-3230.BCD-22-0077","article-title":"Anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with hematologic malignancies.","volume":"3","author":"Greenberger","year":"2022","journal-title":"Blood Cancer Discov"},{"issue":"1","key":"jrv230004r30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/00042728-200501000-00008","article-title":"High recurrence rates of squamous cell carcinoma after Mohs\u2019 surgery in patients with chronic lymphocytic leukemia.","volume":"31","author":"Mehrany","year":"2005","journal-title":"Dermatol Surg"},{"issue":"8","key":"jrv230004r31","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1001\/archderm.140.8.985","article-title":"High recurrence rates of basal cell carcinoma after Mohs surgery in patients with chronic lymphocytic leukemia.","volume":"140","author":"Mehrany","year":"2004","journal-title":"Arch Dermatol"},{"issue":"2","key":"jrv230004r32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1182\/blood.2021014960","article-title":"Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial.","volume":"140","author":"Shanafelt","year":"2022","journal-title":"Blood"},{"issue":"11","key":"jrv230004r33","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1182\/bloodadvances.2021006434","article-title":"Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia.","volume":"6","author":"Barr","year":"2022","journal-title":"Blood Adv"},{"issue":"25","key":"jrv230004r34","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia.","volume":"373","author":"Burger","year":"2015","journal-title":"N Engl J Med"},{"issue":"9","key":"jrv230004r35","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.3324\/haematol.2021.279012","article-title":"First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial.","volume":"107","author":"Moreno","year":"2022","journal-title":"Haematologica"},{"issue":"1","key":"jrv230004r36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1470-2045(18)30788-5","article-title":"Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial.","volume":"20","author":"Moreno","year":"2019","journal-title":"Lancet Oncol"},{"issue":"5","key":"jrv230004r37","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa1817073","article-title":"Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia.","volume":"381","author":"Shanafelt","year":"2019","journal-title":"N Engl J Med"},{"issue":"26","key":"jrv230004r38","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1812836","article-title":"Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL.","volume":"379","author":"Woyach","year":"2018","journal-title":"N Engl J Med"},{"issue":"4","key":"jrv230004r39","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/s41375-021-01485-x","article-title":"Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-na\u00efve chronic lymphocytic leukemia.","volume":"36","author":"Sharman","year":"2022","journal-title":"Leukemia"},{"issue":"8","key":"jrv230004r40","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S1470-2045(22)00293-5","article-title":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.","volume":"23","author":"Tam","year":"2022","journal-title":"Lancet Oncol"},{"issue":"9","key":"jrv230004r41","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/S1470-2045(20)30443-5","article-title":"Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial.","volume":"21","author":"Al-Sawaf","year":"2020","journal-title":"Lancet Oncol"},{"issue":"12","key":"jrv230004r43","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/ajh.25638","article-title":"Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma.","volume":"94","author":"Munir","year":"2019","journal-title":"Am J Hematol"},{"issue":"3","key":"jrv230004r44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia.","volume":"371","author":"Byrd","year":"2014","journal-title":"N Engl J Med"},{"issue":"25","key":"jrv230004r45","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.19.03355","article-title":"ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia.","volume":"38","author":"Ghia","year":"2020","journal-title":"J Clin Oncol"},{"issue":"31","key":"jrv230004r46","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1200\/JCO.21.01210","article-title":"Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial.","volume":"39","author":"Byrd","year":"2021","journal-title":"J Clin Oncol"},{"issue":"4","key":"jrv230004r47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1056\/NEJMoa2211582","article-title":"Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia.","volume":"388","author":"Brown","year":"2023","journal-title":"N Engl J Med"},{"issue":"11","key":"jrv230004r48","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa1315226","article-title":"Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.","volume":"370","author":"Furman","year":"2014","journal-title":"N Engl J Med"},{"issue":"23","key":"jrv230004r49","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1182\/blood-2018-05-850461","article-title":"The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL\/SLL.","volume":"132","author":"Flinn","year":"2018","journal-title":"Blood"},{"issue":"8","key":"jrv230004r50","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1182\/blood.2021015014","article-title":"Enduring undetectable MRD and updated outcomes in relapsed\/refractory CLL after fixed-duration venetoclax-rituximab.","volume":"140","author":"Seymour","year":"2022","journal-title":"Blood"},{"issue":"27","key":"jrv230004r51","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1200\/JCO.2014.55.8262","article-title":"Entering the era of targeted therapy for chronic lymphocytic leukemia: impact on the practicing clinician.","volume":"32","author":"Byrd","year":"2014","journal-title":"J Clin Oncol"},{"issue":"13","key":"jrv230004r52","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1200\/JCO.2016.70.2282","article-title":"BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia.","volume":"35","author":"Woyach","year":"2017","journal-title":"J Clin Oncol"},{"key":"jrv230004r53","doi-asserted-by":"crossref","DOI":"10.1182\/bloodadvances.2022008821","article-title":"BTK and PLCG2 remain unmutated in one third of patients with CLL relapsing on ibrutinib.","author":"Bonfiglio","year":"2023","journal-title":"Blood Adv"},{"issue":"8","key":"jrv230004r54","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1056\/NEJMoa2114110","article-title":"Mechanisms of resistance to noncovalent bruton\u2019s tyrosine kinase inhibitors.","volume":"386","author":"Wang","year":"2022","journal-title":"N Engl J Med"},{"issue":"5","key":"jrv230004r55","doi-asserted-by":"crossref","first-page":"874","DOI":"10.3324\/haematol.2017.182907","article-title":"Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis.","volume":"103","author":"Mato","year":"2018","journal-title":"Haematologica"},{"issue":"20","key":"jrv230004r56","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1182\/blood.2022016953","article-title":"Ventricular arrhythmias and sudden death events following acalabrutinib initiation.","volume":"140","author":"Bhat","year":"2022","journal-title":"Blood"},{"issue":"18","key":"jrv230004r57","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1182\/blood-2016-10-742437","article-title":"Ventricular arrhythmias and sudden death in patients taking ibrutinib.","volume":"129","author":"Lampson","year":"2017","journal-title":"Blood"},{"issue":"4","key":"jrv230004r58","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/leu.2014.247","article-title":"Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation.","volume":"29","author":"Kamel","year":"2015","journal-title":"Leukemia"},{"issue":"5","key":"jrv230004r59","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1097\/CCO.0000000000000871","article-title":"Current status of phosphoinotiside-3 kinase inhibitors in blood cancers.","volume":"34","author":"Shouse","year":"2022","journal-title":"Curr Opin Oncol"},{"issue":"16","key":"jrv230004r60","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1200\/JCO.18.01460","article-title":"Final results of a randomized, phase III study of rituximab with or without idelalisib followed by open-label idelalisib in patients with relapsed chronic lymphocytic leukemia.","volume":"37","author":"Sharman","year":"2019","journal-title":"J Clin Oncol"},{"issue":"10","key":"jrv230004r61","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1182\/blood.2019004767","article-title":"Breaking through BCL-2 inhibition in CLL.","volume":"135","author":"Chong","year":"2020","journal-title":"Blood"},{"issue":"21","key":"jrv230004r62","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1056\/NEJMct1114348","article-title":"Anti-CD20 antibody therapy for B-cell lymphomas.","volume":"366","author":"Maloney","year":"2012","journal-title":"N Engl J Med"},{"issue":"1","key":"jrv230004r63","doi-asserted-by":"crossref","DOI":"10.1097\/HS9.0000000000000336","article-title":"Long term follow-up data and health-related quality of life in frontline therapy of fit patients treated with FCR versus BR (CLL10 trial of the GCLLSG).","volume":"4","author":"Kutsch","year":"2020","journal-title":"Hemasphere"},{"issue":"6","key":"jrv230004r64","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jclinepi.2004.10.017","article-title":"Cumulative Illness Rating Scale was a reliable and valid index in a family practice context.","volume":"58","author":"Hudon","year":"2005","journal-title":"J Clin Epidemiol"},{"issue":"7","key":"jrv230004r65","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S1470-2045(16)30051-1","article-title":"First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.","volume":"17","author":"Eichhorst","year":"2016","journal-title":"Lancet Oncol"},{"issue":"7","key":"jrv230004r66","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/leu.2015.14","article-title":"Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study.","volume":"29","author":"Goede","year":"2015","journal-title":"Leukemia"},{"issue":"4","key":"jrv230004r67","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1111\/bjh.17984","article-title":"Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a?pooled analysis from four clinical trials.","volume":"196","author":"Allan","year":"2022","journal-title":"Br J Haematol"},{"issue":"9","key":"jrv230004r68","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.3324\/haematol.2020.259432","article-title":"Zanubrutinib monotherapy for patients with treatment na\u00efve chronic lymphocytic leukemia and 17p deletion.","volume":"106","author":"Tam","year":"2020","journal-title":"Haematologica"},{"issue":"2","key":"jrv230004r69","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2015-06-651125","article-title":"Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial.","volume":"127","author":"Fischer","year":"2016","journal-title":"Blood"},{"issue":"19","key":"jrv230004r70","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1200\/JCO.2017.76.6840","article-title":"Venetoclax for patients with chronic lymphocytic leukemia with 17p deletion: results from the full population of a phase II pivotal trial.","volume":"36","author":"Stilgenbauer","year":"2018","journal-title":"J Clin Oncol"},{"issue":"1","key":"jrv230004r71","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(17)30909-9","article-title":"Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.","volume":"19","author":"Jones","year":"2018","journal-title":"Lancet Oncol"},{"issue":"14","key":"jrv230004r72","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1158\/1078-0432.CCR-19-3815","article-title":"Assessment of the efficacy of therapies following venetoclax discontinuation in CLL reveals BTK inhibition as an effective strategy.","volume":"26","author":"Mato","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"12","key":"jrv230004r73","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1056\/NEJMoa1713976","article-title":"Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia.","volume":"378","author":"Seymour","year":"2018","journal-title":"N Engl J Med"},{"issue":"3","key":"jrv230004r74","doi-asserted-by":"crossref","first-page":"E105","DOI":"10.1002\/ajh.26444","article-title":"A multicenter, retrospective study of accelerated venetoclax ramp-up in patients with relapsed\/refractory chronic lymphocytic leukemia.","volume":"97","author":"Davids","year":"2022","journal-title":"Am J Hematol"},{"issue":"15","key":"jrv230004r75","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.1182\/bloodadvances.2022007812","article-title":"Venetoclax retreatment of patients with chronic lymphocytic leukemia after a previous venetoclax-based regimen.","volume":"6","author":"Thompson","year":"2022","journal-title":"Blood Adv"},{"issue":"10","key":"jrv230004r76","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.3109\/10428194.2015.1022770","article-title":"Management of adverse events associated with idelalisib treatment: expert panel opinion.","volume":"56","author":"Coutr\u00e9","year":"2015","journal-title":"Leuk Lymphoma"},{"issue":"2","key":"jrv230004r77","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1182\/blood-2016-03-707133","article-title":"Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity.","volume":"128","author":"Lampson","year":"2016","journal-title":"Blood"},{"issue":"10277","key":"jrv230004r78","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/S0140-6736(21)00224-5","article-title":"Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1\/2 study.","volume":"397","author":"Mato","year":"2021","journal-title":"Lancet"},{"issue":"24","key":"jrv230004r79","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1056\/NEJMoa1400029","article-title":"Resistance mechanisms for the Bruton\u2019s tyrosine kinase inhibitor ibrutinib.","volume":"370","author":"Woyach","year":"2014","journal-title":"N Engl J Med"},{"issue":"9","key":"jrv230004r80","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1182\/bloodadvances.2018030007","article-title":"Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib.","volume":"3","author":"Awan","year":"2019","journal-title":"Blood Adv"},{"issue":"S2","key":"jrv230004r81","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/hon.29_2629","article-title":"PHASE 2 study of acalabrutinib in ibrutinib-intolerant patients with relapsed\/refractory chronic lymphocytic leukemia.","volume":"37","author":"Rogers","year":"2019","journal-title":"Hematol Oncol"},{"issue":"1","key":"jrv230004r82","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1016\/S2352-3026(22)00320-9","article-title":"Zanubrutinib in patients with previously treated B-cell malignancies intolerant of previous Bruton tyrosine kinase inhibitors in the USA: a phase 2, open-label, single-arm study.","volume":"10","author":"Shadman","year":"2023","journal-title":"Lancet Haematol"},{"issue":"4","key":"jrv230004r83","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.hoc.2021.03.011","article-title":"Immune therapy for chronic lymphocytic leukemia: allogeneic transplant, chimeric antigen receptor T-cell therapy, and beyond.","volume":"35","author":"Shadman","year":"2021","journal-title":"Hematol Oncol Clin North Am"},{"issue":"16","key":"jrv230004r84","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1182\/bloodadvances.2020001956","article-title":"Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents.","volume":"4","author":"Roeker","year":"2020","journal-title":"Blood Adv"},{"issue":"7897","key":"jrv230004r85","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-021-04390-6","article-title":"Decade-long leukaemia remissions with persistence of CD4+ CAR T cells.","volume":"602","author":"Melenhorst","year":"2022","journal-title":"Nature"},{"issue":"12","key":"jrv230004r86","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1182\/blood.2021011895","article-title":"Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed\/refractory CLL or SLL.","volume":"139","author":"Siddiqi","year":"2022","journal-title":"Blood"},{"issue":"2","key":"jrv230004r87","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1200\/JCO.22.01028","article-title":"Emerging therapies for the management of Richter transformation.","volume":"41","author":"Smyth","year":"2023","journal-title":"J Clin Oncol"},{"issue":"11","key":"jrv230004r88","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.3324\/haematol.2020.256388","article-title":"Hodgkin lymphoma arising in patients with chronic lymphocytic leukemia: outcomes from a large multi-center collaboration.","volume":"106","author":"Stephens","year":"2021","journal-title":"Haematologica"},{"key":"jrv230004r1","unstructured":"Cancer Stat Facts: Leukemia\u2014chronic lymphocytic leukemia (CLL). National Cancer Institute. Published 2022. Accessed February 21, 2023. https:\/\/seer.cancer.gov\/statfacts\/html\/clyl.html"},{"key":"jrv230004r26","unstructured":"Pneumococcal vaccine timing for adults. Centers for Disease Control and Prevention Published February 8, 2022. Accessed February 22, 2023. https:\/\/www.cdc.gov\/vaccines\/vpd\/pneumo\/downloads\/pneumo-vaccine-timing.pdf"},{"key":"jrv230004r27","unstructured":"COVID-19 vaccines for people who are moderately or severely immunocompromised. Centers for Disease Control and Prevention. Updated January 31, 2023. Accessed February 22, 2023. https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/vaccines\/recommendations\/immuno.html"},{"key":"jrv230004r28","unstructured":"Chronic lymphocytic leukemia\/small lymphocytic lymphoma (version 1.2023) National Comprehensive Cancer Network. Published 2023. https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/cll.pdf"},{"key":"jrv230004r42","doi-asserted-by":"crossref","unstructured":"Kater? AP, Owen? C, Moreno? C, Follows? G, Munir? T, Levin? M-D, . Fixed-duration ibrutinib-venetoclax in patients with chronic lymphocytic leukemia and comorbidities. NEJM Evidence. Published May 13, 2022. Accessed February 22, 2023. https:\/\/evidence.nejm.org\/doi\/full\/10.1056\/EVIDoa2200006","DOI":"10.1056\/EVIDoa2200006"}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/articlepdf\/2802611\/jama_shadman_2023_rv_230004_1679344287.92157.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T11:05:54Z","timestamp":1679396754000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2802611"}},"subtitle":["A Review"],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":88,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,3,21]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2023.1946","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3,21]]}}}