{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:25:12Z","timestamp":1790673912372,"version":"4.1.0"},"reference-count":37,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"15","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2021,5,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R\/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3K\u03b4\/casein kinase-1\u03b5, exhibits improved selectivity for PI3K\u03b4 compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of umbralisib in patients with R\/R iNHL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>In this multicohort, open-label, phase IIb study, 208 patients with R\/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) unresponsive to prior treatments (\u2265 1 MZL; \u2265 2 FL\/SLL), including \u2265 1 anti-CD20\u2013based therapy, were administered umbralisib 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal. Primary end point is overall response rate; secondary end points include time to response, duration of response, progression-free survival, and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The median follow-up is 27.7 months (efficacy) and 21.4 months (safety). The overall response rate was 47.1%, and tumor reduction occurred in 86.4% of patients. The median time to response was 2.7-4.6 months. The median duration of response was not reached for MZL, 11.1 months for FL, and 18.3 months for SLL. Median progression-free survival was not reached for MZL, 10.6 months for FL, and 20.9 months for SLL. At least one grade \u2265 3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). A total of 31 patients (14.9%) discontinued because of a treatment-related adverse event. Grade \u2265 3 TEAEs reported in \u2265 10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT\/AST (grade \u2265 3) occurred in 6.7%\/7.2% of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event\u2013related discontinuations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.20.03433","type":"journal-article","created":{"date-parts":[[2021,3,8]],"date-time":"2021-03-08T15:59:23Z","timestamp":1615219163000},"page":"1609-1618","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":154,"title":["Umbralisib, a Dual PI3K\u03b4\/CK1\u03b5 Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma"],"prefix":"10.1200","volume":"39","author":[{"given":"Nathan H.","family":"Fowler","sequence":"first","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Samaniego","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, 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