Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: NHL – New Drugs
Methods: In this phase 2 trial, pts aged ≥18 years with relapsed/refractory NHL or CLL received oral abexinostat at 80 mg BID for 14 days of a 21-day cycle and continued until progressive disease or unacceptable toxicity. The 80 mg BID dose, which corresponds to the recommended phase 2 dose of 45 mg/m2 BID, was identified in phase 1 of the study (Morschhauser, Invest New Drugs, 2015). The primary endpoint was overall response rate (ORR); secondary endpoints included overall survival, progression-free survival, time to tumor progression, duration of response, disease-free survival, and time to treatment failure.
Results: A total of 100 pts (median age, 66.5 years; 52% >65 years; 55% male) were enrolled between Oct 2011 and Jul 2014, including 16 with CLL, 17 with diffuse large B-cell lymphoma (DLBCL), 18 with FL, 16 with mantle cell lymphoma (MCL), 18 with T-CL, and 15 with marginal zone lymphoma (MZL) or other NHL subtypes. The median number of prior regimens across all lymphoma subtypes was 3 (range, 1-11) with a median of 4.5 prior regimens (range, 1-11) for FL pts. All pts received at least one dose of study drug; 55% discontinued due to progressive disease and 25% due to adverse events. Seven pts remain on treatment. Among the 87 pts evaluable for efficacy, ORR was 28% (CR, 5%). Responses by histology are shown in the table. Highest responses were observed in FL, T-CL, and DLBCL with ORRs of 56%, 40%, and 31% and median durations of response of 26.0 weeks (range, 0.1-90.4), 32.1 weeks (range, 6.3-51.3), and 8.1 weeks (range, 3.1-59.0), respectively. Grade ≥3 adverse events (AEs) and any serious AEs (SAEs) were reported in 86% and 46% of pts, respectively. The most frequently reported grade ≥3 treatment-emergent AEs were thrombocytopenia (80%), neutropenia (27%), and anemia (22%). The incidence of any-grade diarrhea was 47% (grade ≥3, 3%). The most commonly reported SAEs included thrombocytopenia (15%), anemia (7%), and pneumonia (6%). The most frequent toxicities that led to discontinuation included hematologic events, such as thrombocytopenia and neutropenia. Gastrointestinal toxicities leading to discontinuation were infrequent with 1 episode of vomiting being reported.
Conclusions: Abexinostat has a manageable toxicity profile in pts with various NHL subtypes that is similar to other HDACi and comparable to other single-agent therapies currently in development. Promising efficacy was observed with abexinostat, especially in FL, T-CL, and DLBCL, with an ORR ≥30% in these subtypes, consistent with the results of an independent study of abexinostat in lymphomas that used a week-on-week-off schedule (Evens ICML 2013). Further investigation of the safety and efficacy of abexinostat in these indications implementing the less dose-intense interval on a week-on-week-off schedule is planned.
Table: Response With Abexinostat by Tumor Type
Tumor type |
ORR, % (CR, %) |
Overall (N=87) |
28% (5%) |
FL (n=16) |
56% (6%) |
T-CL (n=15) |
40% (7%) |
DLBCL (n=16) |
31% (6%) |
MCL (n=13) |
15% (8%) |
MZL/other (n=13) |
15% (0%) |
CLL (n=14) |
0% (0%) |
Disclosures: Ribrag: Pharmamar: Honoraria , Membership on an entity’s Board of Directors or advisory committees ; Gilead: Membership on an entity’s Board of Directors or advisory committees ; Servier: Consultancy , Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding . Off Label Use: abexinostat in NHL and CLL. Coiffier: CELLTRION, Inc.: Consultancy , Honoraria ; Gilead Sciences: Research Funding . Luan: Pharmacyclics LLC, an AbbVie Company: Employment . Graef: AbbVie: Equity Ownership ; Pharmacyclics LLC, an AbbVie Company: Employment , Membership on an entity’s Board of Directors or advisory committees . Morschhauser: Genentech Inc./Roche: Other: Advisory boards .
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