{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:04:59Z","timestamp":1793444699093,"version":"4.5.0"},"reference-count":57,"publisher":"American Society for Clinical Investigation","issue":"9","funder":[{"name":"National Cancer Institute","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Subgroups of patients with relapsed or refractory (R\/R) chronic lymphocytic leukemia (CLL) exhibit suboptimal outcomes after standard therapies, including oral kinase inhibitors. We and others have previously reported on the safety and efficacy of autologous CD19-targeted CAR T cells for these patients. Here, we report safety and long-term follow-up of CAR T cell therapy with or without conditioning chemotherapy for patients with R\/R CLL and indolent B cell non-Hodgkin lymphoma (B-NHL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted a phase I clinical trial investigating CD19-targeted CAR T cells incorporating a CD28 costimulatory domain (19\u201328z). Seventeen of twenty patients received conditioning chemotherapy prior to CAR T cell infusion. Five patients with CLL received ibrutinib at the time of autologous T cell collection and\/or CAR T cell administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      This analysis included 16 patients with R\/R CLL and 4 patients with R\/R indolent B-NHL. Cytokine release syndrome (CRS) was observed in all 20 patients, but grade 3 and 4 CRS and neurological events were uncommon (10% for each). Ex vivo expansion of T cells and proportions of CAR T cells with the CD62L\n                      <jats:sup>+<\/jats:sup>\n                      CD127\n                      <jats:sup>+<\/jats:sup>\n                      immunophenotype were significantly greater (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.047; CD8 subset,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0061, CD4 subset) in patients on ibrutinib at leukapheresis. Three of twelve evaluable CLL patients receiving conditioning chemotherapy achieved complete response (CR) (2 had minimal residual disease\u2013negative CR). All patients achieving CR remained progression free at median follow-up of 53 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Conditioning chemotherapy and 19\u201328z CAR T cells were acceptably tolerated across investigated dose levels in heavily pretreated patients with R\/R CLL and indolent B-NHL, and a subgroup of patients achieved durable CR. Ibrutinib therapy may modulate autologous T cell phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT00466531.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Juno Therapeutics and NIH\/National Cancer Institute Cancer Center Support Grant (P30-CA08748).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.122627","type":"journal-article","created":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T12:01:32Z","timestamp":1554206492000},"source":"Crossref","is-referenced-by-count":86,"title":["Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed\/refractory CLL"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-9117","authenticated-orcid":true,"given":"Mark B.","family":"Geyer","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"Center for Cell Engineering,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Center for Cell Engineering,"},{"name":"Michael G. 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Harris Cell Therapy and Cell Engineering Facility,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J.","family":"Purdon","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meier","family":"Hsu","sequence":"additional","affiliation":[{"name":"Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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