Expert Point of View: Susan O'Brien, MD, and Bruce Cheson, MD


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Susan O’Brien, MD

Susan O’Brien, MD

SUSAN O’BRIEN, MD, Associate Director for Clinical Science, Chao Family Comprehensive Cancer Center, University of California Irvine Health, told The ASCO Post that the pairing of ibrutinib (Imbruvica) and venetoclax (Venclexta) “is clearly a very powerful combination.” The next question, she said, is whether an antibody would add even more to this doublet. In phase II trials of ibrutinib plus rituximab (Rituxan) or ofatumumab (Arzerra), outcomes were similar to those seen with single-agent ibrutinib, but the same is not true for venetoclax plus an antibody, she pointed out. 

“It looks like there is clearly synergy between venetoclax and rituximab or obinutuzumab [Gazyva],” she said, noting that minimal residual disease (MRD) negativity rates for these doublets have been about 80% or higher in the front-line setting. “Since we do see synergy with venetoclax, perhaps an antibody would add something to this doublet.” 

Supportive Data Build for Chemotherapy-Free Option 

Bruce Cheson, MD

Bruce Cheson, MD

THE ABSTRACT’S invited discussant, Bruce Cheson, MD, Deputy Chief, Division of Hematology/Oncology at Lombardi Comprehensive Cancer Center, Washington, DC, said the addition of ibrutinib and venetoclax to the chronic lymphocytic leukemia (CLL) armamentarium “finally” moves the treatment landscape toward an effective chemotherapy-free option, the supportive data for which have become “substantial.” 

“Dr. O’Brien recently updated the front-line ibrutinib data, showing that without chemotherapy, 92% of CLL patients are progression-free beyond 5 years,” he said.1 Also, the MURANO trial, updated at the 2017 American Society of Hematology (ASH) Annual Meeting, showed venetoclax plus rituximab to be greatly superior to bendamustine plus rituximab, more than doubling the 2-year progression-free survival.2 

“Whether 17p-deleted or not, the chemotherapy-free arm was highly superior to chemo-immunotherapy,” Dr. Cheson noted. 

“And there’s been lots of attention on MRD eradication in CLL,” he continued. Although chemotherapy regimens have resulted in MRD-negativity rates hovering around 35%, ibrutinib/venetoclax produces clinical responses in 100% of patients; all patients with complete remissions also achieved MRD negativity, as did the majority of partial responders, he said. “This is as least as good as we achieve with chemoimmunotherapy,” he added. 

According to Dr. Cheson, patients with CLL to consider for a front-line chemotherapy-free regimen include those with a 17p deletion (in whom chemotherapy is not effective); those older than age 65; patients with comorbidities; patients with unmutated IGHV; and patients willing to be treated with prolonged therapy. “This accounts for more than 80% of our patients with CLL in the front-line,” he said. “And in the relapsed setting, there is no room for chemo anymore.” ■

DISCLOSURE: Dr. O’Brien reported no conflicts of interest. Dr. Cheson has served as a consultant or advisor to AbbVie, Acerta Pharma, Bayer, Morphosys, Pharmacyclics/Janssen, Roche/Genentech, Sunesis Pharmaceuticals, and TG Therapeutics. 

REFERENCES 

1. O’Brien SM, Furman RF, Coutre SE, et al: Five-year experience with single-agent ibrutinib in patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic leukemia. 2016 ASH Annual Meeting. Abstract 233. 

2. Seymour JF, Kipps TJ, Eichhorst BF, et al: Venetoclax plus rituximab is superior to bendamustine plus rituximab in patients with relapsed/refractory chronic lymphocytic leukemia—Results from pre-planned interim analysis of the randomized phase 3 Murano study. 2017 ASH Annual Meeting & Exposition. Abstract LBA-2.


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A REGIMEN COMBINING ibrutinib (Imbruvica) and venetoclax (Venclexta) in previously untreated patients with chronic lymphocytic leukemia (CLL) greatly reduced the risk of venetoclax-associated tumor-lysis syndrome and led to promising rates of undetectable minimal residual disease (MRD) in the phase ...

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