Year: 2017
Type: article
Abstract: Background: VEN is a selective orally bioavailable BCL-2 inhibitor. The dose-escalation Phase 1 study of VEN in 106 patients (pts) with relapsed/refractory NHL reported an ORR of 44%. Most pts had diffuse large B-cell/follicular lymphoma; we report on updated results in pts with less common NHL subtypes. Methods: VEN was administered and continued until progressive disease (PD)/unacceptable toxicity, in dose cohorts ranging from 300 to 1200 mg. Adverse events (AEs) were assessed by NCI-CTCAE v4.0 and response by 2007 Cheson IWG response criteria, utilizing CT scans beginning at wk 6. Results: 35 of 106 pts had mantle cell lymphoma (MCL, n = 28), marginal zone lymphoma (MZL, n = 3) or Waldenström macroglobulinemia (WM, n = 4). Pts were enrolled from Sept 2011 to Aug 2014. The current analysis reports pt status as of Jan 03, 2017. Eight of 35 pts (23%) continue on treatment and the median time on drug for these pts is 34 months (range 30-54). Most common all grade treatment emergent AEs were nausea (51%), diarrhea (49%) and fatigue (34%); grade 3/4 AEs in >10% of pts were neutropenia and anemia (17% each). Laboratory TLS was reported in a single pt who had bulky MCL. The overall rate of infections was 51% and grade 3/4 infections was 23%. MCL pts (median age: 72 years) had received a median of 3 (1-7) prior treatments (tx). Median time from start of prior tx to start of VEN was 13 mo (2-148) and median time from end of prior tx to start of VEN was 8 mo (0.7-147). The median time on VEN was 11 mo (0.2-42). ORR was 75% (n = 21 responders), 6 pts (21%) achieved CR at a median of 4.4 mo (range 1.2-16.1) on VEN. Four pts with CR and two pts with PR remain on study (DORs: 25-40 mo). One pt with a PR proceeded to elective allogeneic stem-cell transplant and remained disease free at last protocol defined follow-up (24 mo after coming off study). Median PFS was 11 mo and DOR was 15 mo for the MCL cohort. MZL pts (median age: 63 years) had received a median of 4 (2-6) prior tx. Time from start of prior tx to start of VEN was 8, 14, 73 mo and time from end of prior tx to start of VEN was 6, 8, 53 mo. Time on VEN was 5, 1, 35 mo. One pt (6 prior tx) received VEN for <1 mo due to progressive cytopenias; 1 pt (4 prior tx) achieved a PR with VEN at wk 6 but had PD at wk 16; 1 pt (2 prior tx) achieved PR at wk 6, with DOR 32+ mo and remains in PR and on study at 35+ mo. WM pts (median age: 67 years) had a median of 4 (3-5) prior tx. Time from start of prior tx to start of VEN was 5, 18, 33, 67 mo and time from end of prior tx to start of VEN was 4, 10, 29, 66 mo and time on VEN was 42, 17, 54, 20 mo. All pts achieved PR (at wks 6 [n = 2], 16 and 36), with DORs of 11, 12, 38 and 50+ mo (latter is ongoing and remains on study at 54+ mo). Conclusions: VEN monotherapy has a tolerable safety profile with a low rate of serious infections in MCL, MZL and WM pts. ORR was high and many responses durable; median PFS and DOR suggest significant activity in MCL pts. Further investigation of VEN in each disease is indicated. Keywords: ABT-199; non-Hodgkin lymphoma (NHL)
Source: Hematological Oncology
DOI: 10.1002/hon.2438_67
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2622065386