Toby Eyre, MCBhB, MRCP, consultant hematologist at Oxford University Hospitals NHS Trust, discusses the potential for BTK inhibitors to be used in combination with venetoclax (Venclexta) for the treatment of patients with mantle cell lymphoma (MCL).

Venetoclax has been extremely effective in patients with chronic lymphocytic leukemia, and it is now being tested with BTK inhibitors in that space. The same thing is starting to happen in MCL, Eyre says. A previous phase I study showed an overall response rate of 75% and a progression-free survival of just under 14 months with venetoclax. Interestingly, similar data has been seen with ibrutinib (Imbruvica). Recent data was published looking at the combination in a small number of patients and it showed efficacy, particularly in terms of complete response rates and minimal residual disease—negativity. The natural next step, Eyre says, is to look at this combination further.

It remains to be seen what the tolerability will be for this combination. Venetoclax and ibrutinib have some overlapping toxicities like diarrhea, cytopenia, and neutropenia.

Videos

Toby Eyre, MBChB, MRCP, consultant hematologist at Oxford University Hospitals NHS Trust, discusses the potential for BTK inhibitors to be used in combination with venetoclax for mantle cell lymphoma.

Dr. Eyre on BTK Inhibitors in Combination With Venetoclax for MCL

Toby Eyre, MBChB, MRCP, consultant hematologist at Oxford University Hospitals NHS Trust, discusses the results of single-agent venetoclax (Venclexta) in patients with relapsed/refractory mantle cell lymphoma (MCL).

There remains an area of unmet need for patients with MCL who relapse after treatment with a BTK inhibitor. In a retrospective study, venetoclax monotherapy induced an overall response rate of 60% in patients with poor-risk relapsed/refractory MCL previously treated with a BTK inhibitor.

Data has been collected on 20 patients, and the response rate is 60% with a complete response rate of 20%. Eyre says that the progression-free survival (PFS) is still fairly limited at just over 3 months, and the overall survival is about 9 months. The drug was well tolerated, Eyre adds, but work still needs to be done in this difficult-to-treat population.

This study utilized the UK Medicines and Healthcare Products Regulatory Agency compassionate use scheme, which Eyre says often includes patients in pretty dire states of disease. In this study in particular, patients had poor-risk clinical features, including a PFS of 4.8 with prior BTK inhibitor therapy.

Toby Eyre, MBChB, MRCP, consultant hematologist at Oxford University Hospitals NHS Trust, discusses the results of single-agent venetoclax (Venclexta) in patients with relapsed/refractory mantle cell lymphoma. 
 

Dr. Eyre on Results of Venetoclax in Relapsed/Refractory MCL

Toby Eyre, MBChB, MRCP, consultant hematologist at Oxford University Hospitals NHS Trust, discusses venetoclax (Venclexta) monotherapy in patients with mantle cell lymphoma (MCL).

Patients with relapsed/refractory MCL have a poor prognosis, with an approximate overall survival of 2 years, says Eyre. Even with the success of BTK inhibitors, many patients relapse, creating an area of unmet need. In a study of patients with poor-risk relapsed/refractory MCL previously treated with a BTK inhibitor, venetoclax monotherapy induced an overall response rate of 60%. Of the responders, 20% had a complete response.

These data come from the UK Medicines and Healthcare Products Regulatory Agency compassionate use scheme, says Eyre. The majority of these patients received ibrutinib (Imbruvica), but some had received other BTK inhibitors while on a clinical trial. These 20 patients went on to received venetoclax monotherapy, but the efficacy data was not collected in the post-BTK inhibitor setting until this study.

Toby Eyre, MBChB, MRCP, consultant hematologist at Oxford University Hospitals NHS Foundation Trust, discusses venetoclax (Venclexta) monotherapy in patients with mantle cell lymphoma.

Toby Eyre, MBChB, MRCP

Articles

Dr. Eyre on BTK Inhibitors in Combination With Venetoclax for MCL

Dr. Eyre on Results of Venetoclax in Relapsed/Refractory MCL

Dr. Eyre Discusses Venetoclax Monotherapy in MCL