Venclexta Shows Potential to Treat Mantle Cell Lymphoma, Unmet Needs Remain

Patients with mantle cell lymphoma (MCL) who were treated with Venclexta (venetoclax) showed a slight improvement in response rates compared with chemoimmunotherapy, according to retrospective study results presented at the 2018 European Hematology Association (EHA) Congress.

Single-agent Venclexta induced a 60 percent overall response rate (ORR) in 20 patients with poor-risk, relapsed/refractory MCL who were previously treated with a BTK inhibitor, such as Imbruvica (ibrutinib). Additionally, 20 percent of patients experienced a complete response (CR).

The study was conducted in the United Kingdom, where Venclexta was given to patients with relapsed/refractory MCL free of charge as part of the UK Medicines and Healthcare Products Regulatory Agency compassionate use scheme — a treatment option that allows the use of an unauthorized medicine.

“It is well known in MCL that the relapsed/refractory prognosis is poor,” lead author Toby Eyre, MBChB, MRCP, a consultant hematologist at Oxford University Hospitals NHS trust, said in an interview with OncLive, a sister publication of CURE.

“There is an overall survival of approximately two years, even with the addition of BTK inhibitors and other novel therapies,” he added. “There remains an area of real unmet need with regard to the therapeutic approach after BTK inhibitor relapse.”

Even though more than half of patients responded to Venclexta in the study, progression-free (PFS) and overall survival (OS) intervals were still limited to about three months and eight to nine months, respectively. However, Venclexta — a drug commonly used to treat chronic lymphocytic leukemia (CLL) – also appeared to be well-tolerated among patients.

“There is still clearly work to be done, but the drug was very well tolerated in a very difficult-to-treat population,” Eyre said.

A previous phase 1 study of Venclexta in patients with MCL showed an ORR of 75 percent and PFS of just under 14 months. In addition, Eyre noted there were in vitro data and some cell line data at the Congress that demonstrated a potential synergy with the combination use of Venclexta and Imbruvica.

Therefore, the “natural” next step, he added, would be to combine Venclexta with a BTK inhibitor — something currently being done in a large, international, randomized study. Eyre has high hopes for the study but is also eager to see how patients will tolerate the combination, since Venclexta and BTK inhibitors have some overlapping side effects, such as diarrhea, cytopenia and neutropenia.

“We will have to see about the tolerability in the relapsed/refractory setting in MCL. If the combinations are not tolerated, then sequential therapy may be required. In that case, these data may become more relevant,” Eyre said.

Either way, the agent appears to have potential implications for those with such a dire unmet need.

“In terms of the PFS, it is similar to chemoimmunotherapy, but perhaps in a less toxic way. Clearly, these patients coming through a compassionate use program in the United Kingdom were heavily pretreated,” Eyre said.