{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:46:23Z","timestamp":1793040383914,"version":"4.5.0"},"reference-count":18,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Marginal zone lymphoma (MZL) is challenging to treat, with many patients relapsing following initial treatment. We report the long-term efficacy and safety of copanlisib, a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor, in the subset of 23 patients with relapsed\/refractory MZL treated in the phase 2 CHRONOS-1 study (#NCT01660451, Part B; www.clinicaltrials.gov). Patients had a median of 3 prior lines of therapy, including rituximab and alkylating agents, and received IV copanlisib 60 mg on days 1, 8, and 15 of 28-day cycles for a median of 23 weeks. The objective response rate was 78.3% (18\/23; 3 complete responses and 15 partial responses). The median duration of response was 17.4 months (median follow-up, 9.4 months), and median time to response was 2.1 months. Median progression-free survival was 24.1 months (median follow-up, 10.3 months), and median overall survival was not reached (median follow-up, 28.4 months). The most common all-grade treatment-emergent adverse events (TEAEs) included fatigue (52.2%, 12\/23), diarrhea, and transient, infusion-related hyperglycemia (each 47.8%, 11\/23). Nineteen patients (82.6%) had grade 3\/4 TEAEs, most commonly transient, infusion-related hyperglycemia and hypertension (each 39.1%, 9\/23). TEAEs led to dose reduction or dose interruptions \/delays in 9 patients (39.1%) and 18 patients (78.3%), respectively. Patients with activated PI3K\/B-cell antigen receptor signaling had improved response rates. Overall, copanlisib demonstrated strong efficacy, with a short time to objective response, improved objective response rate with longer treatment duration, durable responses, and manageable safety, in line with previous reports. These data provide rationale for long-term treatment with copanlisib in patients with relapsed\/refractory MZL.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002910","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T15:46:43Z","timestamp":1617119203000},"page":"823-828","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":27,"title":["Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-3993","authenticated-orcid":false,"given":"Panayiotis","family":"Panayiotidis","sequence":"first","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Follows","sequence":"additional","affiliation":[{"name":"Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Mollica","sequence":"additional","affiliation":[{"name":"Maisonneuve-Rosemont Hospital Research Centre, Montr\u00e9al, QC, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Nagler","sequence":"additional","affiliation":[{"name":"Chaim Sheba Medical Center, Tel Aviv University, Tel HaShomer, Israel;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-1918","authenticated-orcid":false,"given":"Muhit","family":"\u00d6zcan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ankara University, Ankara, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Santoro","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Department of Biomedical Sciences, Humanitas University, Rozzano, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Stevens","sequence":"additional","affiliation":[{"name":"Norton Cancer Institute, Louisville, KY;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Trevarthen","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Care and Research Institute of Colorado, Englewood, CO;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-5093","authenticated-orcid":false,"given":"Florian","family":"Hiemeyer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Division, Bayer AG, Berlin, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Garcia-Vargas","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals, Inc, Whippany, NJ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9801-4619","authenticated-orcid":false,"given":"Barrett H.","family":"Childs","sequence":"additional","affiliation":[{"name":"Bayer HealthCare Pharmaceuticals, Inc, Whippany, NJ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Zinzani","sequence":"additional","affiliation":[{"name":"IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;"},{"name":"Istituto di Ematologia \u201cSer\u00e0gnoli,\" Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Universit\u00e0 degli Studi, Bologna, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dreyling","sequence":"additional","affiliation":[{"name":"LMU Hospital, Department of Medicine III, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"2021033015463723400_B1","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues","author":"Swerdlow","year":"2017","edition":"revised 4th ed"},{"issue":"1","key":"2021033015463723400_B2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.annonc.2019.10.010","article-title":"Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Zucca","year":"2020","journal-title":"Ann Oncol"},{"key":"2021033015463723400_B3","author":"US Food and Drug 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