Top Takeaways from ASH: Venetoclax represents ‘exciting’ option for CLL

Phase 2 study results of venetoclax presented at the ASH Annual Meeting and Exposition represent “a huge advancement” in the treatment of patients with relapsed and/or refractory chronic lymphocytic leukemia with deletion of 17p.

The single-arm, multicenter trial conducted by Stephan Stilgenbauer, MD, PhD, professor in the department of internal medicine at University of Ulm in Germany, and colleagues included 107 patients (median age, 67 years; range 37-85) with relapsed/refractory CLL; men composed 65% of the cohort. Participants had been treated with a median of two prior regimens (range, 1-10).

The overall response rate was 79.4% (95% CI, 70.5-86.6), with deep responses in 7.5% of patients who achieved complete remission or complete remission with incomplete hematologic recovery (CRi) and 2.8% of patients with nodular partial remission. Median time to first response was 0.8 months (range, 0.1-8.1) and median time to complete remission or CRi was 8.2 months (range 3-16.3). Among 45 patients who underwent a minimal residual disease (MRD) assessment, 18 patients had no detectable MRD in the peripheral blood and six patients had no MRD in the bone marrow.

Grade 3 to grade 4 adverse events included neutropenia (40%), anemia (18%) and thrombocytopenia (15%), although the researchers noted that 22.4% of patients had neutropenia at the start of the study. Grade 3 or worse infections occurred in 20% of patients, including pneumonia (5%), and five patients reported laboratory tumor lysis syndrome, but none resulted in a negative clinical outcome.

Nilanjan Ghosh, MD, PhD, director of the lymphoma program and associate director of clinical trials in the Department of Hematologic Oncology and Blood Disorders at the Levine Cancer Institute, Carolinas HealthCare System, and Ryan Jacobs, MD, of the Department of Hematologic Oncology and Blood Disorders at the Levine Cancer Institute, discussed the potential implications of the study results with Healio.com.

Venetoclax, other recent approvals lead to resurgence of progress in CLL

According to Ghosh, multiple outcomes seen in this study make venetoclax (ABT-199/GDC-0199; AbbVie, Genentech) “a really exciting drug.”

Nilanjan Ghosh

“Until recently, patients with CLL with deletion of 17p had very poor outcomes,” Ghosh said. “In this relapsed, refractory population, there is no other single agent that has shown complete responses. Venetoclax is a huge advancement.”

The emergence of a “renaissance period” in CLL has been described by many experts, including Jeff Sharman, MD, director of research at Willamette Valley Cancer Institute and Research Center in Eugene, OR, and medical director of hematology research for the US Oncology Network, and others. Jacobs highlighted the recent FDA approvals of ibrutinib (Imbruvica; Pharmacyclics, Janssen) and idelalisib (Zydelig, Gilead) for CLL in addition to the ASH data on venetoclax as integral parts of this period.

Ryan Jacobs

“What’s been a little bit frustrating with some of these other agents, like ibrutinib or idelalisib, is that while there are amazing response rates –complete responses are lacking,” he said. “Venetoclax yielded complete response rates as a single agent in a relapsed, refractory population treated with a median of two prior regimens.”

Ghosh also alluded to the role venetoclax could have in altering the current treatment landscape for CLL.

“We know that venetoclax has very good activity after failure of the two kinase inhibitors that have already been approved in CLL,” he said. “It’s good to know that there are options beyond ibrutinib or idelalisib. This is knowledge that needs to be out there.”

These ongoing developments make it “an exciting time” to be involved in the research and treatment of CLL, according to Jacobs.

“There’s been this birth of new drugs, some of which are approved, and there are more on the way,” he said. “I think we’re going to end up seeing similar things happening in CLL like what has been in multiple myeloma over the past decade, where, by and large, we move away from chemotherapy and use a lot of these newer, mostly oral compounds.” – by Julia Ernst, MS

References:

Jones J, et al. Abstract 715. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Stilgenbauer S, et al. Abstract LBA-6. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Disclosure: Stilgenbauer reports research funding and honoraria from and advisory board roles with AbbVie, Amgen, Boehringer Ingelheim, Celgene, Genentech, Genzyme, Gilead, GlaxoSmithKline, Janssen, Mundipharma, Novartis, Pharmacyclics and Roche. Ghosh and Jacobs report no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.