SOHO 2017 | Outcomes and MRD analysis in the pivotal M13-982 trial of venetoclax for R/R del(17p) patients

The fifth Annual Meeting of the Society of Hematologic Oncology (SOHO) took place at the Westin Galleria in Houston, Texas, between 13^th–16^th September 2017.

In 2012, SOHO was established and the society “aims to promote worldwide research, education, prevention, clinical studies and optimal patient care in all aspects of hematologic malignancies and related disorders.” SOHO has over 2,000 members and is led by a Board of Directors with six voting members, a Steering Committee of clinician-scientists, a Scientific Committee, and an Education Committee.

The 2017 meeting was a dynamic and informative event with internationally recognized speakers representing the spectrum of hem-onc diseases. This year, it is thought that over 1,000 physicians, nurses, and related healthcare specialists attended the 3.5-day event.

The ninth session of the meeting was dedicated to Chronic Lymphocytic Leukemia (CLL), took place on 16^th September 2017, and was co-chaired by Michael J. Keating, MB BS, from the University of Texas MD Anderson Cancer Center, Houston, Texas, USA, and Emili Montserrat, MD, PhD, from the Hospital Clinic Barcelona, Barcelona, Spain.

One of the oral abstracts (CLL-102) presented during this session focused on outcomes and Minimal Residual Disease (MRD) in the pivotal M13-982 trial of venetoclax in Relapsed/Refractory (R/R) CLL with del(17p).

This abstract was presented by William Wierda, MD, also from the University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Venetoclax was administered to patients (n=158) at a dose of 400mg daily after initial ramp-up until disease progression or discontinuation. Data cut-off was 10^th June 2016.

Patients:

• Median age = 67 years (range, 29–85)
• Median number of prior therapies = 2 (range, 0–10); 32% refractory to fludarabine; 11% previously received B-cell receptor inhibitor
• Nearly half (48%) had nodes ≥5cm
• Unmutated IGHV = 78%
• Median duration on venetoclax = 16.7 months (range, 0–34.4)
• Reasons for discontinuation = PD (31.0%), AEs (12.6%), consent withdrawal (2.5%), SCT (2.5%), and other reasons (1.9%)

Efficacy:

• Investigator-assessed ORR = 77%; CR = 18%
• 2-year estimated PFS = 52%; 2-year estimated OS = 72%
• ORR of 5 newly diagnosed pts in expansion cohort = 80%; CR = 40%; all alive and progression free after 12 months
• ORR in patients with prior B-cell receptor inhibitor (n=18) = 61%; CR = 11%; 12-month estimated PFS = 50%; 12-month estimated OS = 72%

MRD analysis:

• Pts with evaluable blood MRD by flow = 101; also with Next-Generation Sequencing (NGS) data = 76
• Blood MRD-negativity by flow = 42/158 (27%); 28 had contemporaneous NGS samples
• MRD-negativity by NGS = 20 pts (71%); MRD-positivity by NGS = 8 pts (22%)
• Blood MRD-negativity by NGS was observed in 22 pts; 9 also negative in bone marrow
• 2-year estimated PFS was 100% in pts who achieved blood MRD-negative CR by flow (n=19) compared to 78.5% for blood MRD-negative PR pts (n=23)
• Similar observed by NGS

The abstract presentation was concluded by stating that durable, high response rates were achieved with the BCL-2 inhibitor venetoclax in this high-risk patient population. Furthermore, achievement of MRD-negativity by flow or NGS was associated with optimistic outcomes.

During iwCLL 2017, the Lymphoma Hub reported on a presentation given by Danielle Brander, MD, from the Duke Cancer Institute, Durham, North Carolina, USA, who reported results from the phase Ib, open-label, dose-escalation M13-365 trial of venetoclax plus rituximab for R/R CLL (NCT01682616); read more here.

Abstract:

Venetoclax in patients with relapsed/refractory del(17p) CLL resulted in an ORR of 79% (7% CR) at the initial analysis of the M13-982 trial (n=107). Subsequently, 51 patients were enrolled in a safety expansion cohort.