{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:35:48Z","timestamp":1793842548448,"version":"4.6.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Trial Information<\/jats:title>\n                  <jats:p>ClinicalTrials.gov \u00a0Identifier: NCT02091063 Sponsor: Acetylon Pharmaceuticals Principal Investigator: Jennifer E. Amengual IRB Approved: Yes<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Lessons Learned<\/jats:title>\n                  <jats:p>Oral selective HDAC6 inhibitors could allow for decreased toxicity compared to pan-class inhibitors, and increased ease of use. ACY-1215 is well tolerated and led to disease stabilization in 50% of patients treated on a twice-daily dosing schedule. Rational drug combinations with ACY-1215 improve efficacy in patients with lymphoma. Biomarkers such as XBP-1 level or HDAC6-score may improve patient selection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>ACY-1215, ricolinostat, is an oral, first-in-class isoform-selective HDAC6 inhibitor. HDAC6 is a class IIb deacetylase and plays a critical role in protein homeostasis via the unfolded protein response (UPR). Lymphocytes generate a large repertoire of antibodies and depend on an activated UPR to maintain proteostasis. Lymphomas utilize this biology to evade programmed cell death. In preclinical models of lymphoma, ACY-1215 disrupted proteostasis, triggering apoptosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We translated these findings into a multi-institution, open-label, dose-escalation phase Ib\/II study aimed to determine the safety and efficacy in patients with relapsed and refractory lymphoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-one patients with heavily pretreated lymphoma were accrued. Patients in the phase Ib portion were enrolled on one of two dose cohorts [Arm A: 160 mg daily (n = 3) or Arm B: 160 mg twice daily (n = 10)]. ACY-1215 was well tolerated. There were no dose limiting toxicities. Most adverse events were grade 1\u20132, including diarrhea (57%), nausea (57%), and fatigue (43%). Grade 3\u20134 toxicities were rare and included anemia (9.5%) and hypercalcemia (9.5%). An additional 8 patients were enrolled on the phase II portion, at 160 mg twice daily. Sixteen patients were evaluable for response. ACY-1215 did not result in any complete or partial responses in patients treated. Eight patients had stable disease (50%) lasting a median duration of 4.5 months, all of whom were treated twice daily. Disease progressed in eight patients (50%) at cycle 2. Five patients were not evaluable due to disease progression prior to cycle 2. The median PFS was 56 days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ACY-1215 is an oral selective HDAC6 inhibitor that was safe in patients with relapsed and refractory lymphoid malignancies and led to disease stabilization in half of the evaluable patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/onco.13673","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T07:00:17Z","timestamp":1610953217000},"page":"184-e366","source":"Crossref","is-referenced-by-count":56,"title":["First-in-Class Selective HDAC6 Inhibitor (ACY-1215) Has a Highly Favorable Safety Profile in Patients with Relapsed and Refractory Lymphoma"],"prefix":"10.1093","volume":"26","author":[{"given":"Jennifer E.","family":"Amengual","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Lue","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Lichtenstein","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijal","family":"Shah","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center, Tampa, Florida, 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