Although Venclexta is not FDA approved for use in Multiple Myeloma (MM), some research indicates that it may be promising for some MM patients who have failed at least one prior treatment, especially those with the genetic abnormality t(11;14) or with high levels of BCL-2. However, its use is not without controversy.

One major trial investigating the use of Venclexta for relapsed and refractory MM was halted early by the FDA due to safety concerns. The BELLINI clinical trial used a regimen of Venclexta plus bortezomib (a protease inhibitor) plus dexamethasone for 291 patients with MM. Unfortunately, interim results at an average of 17.9 months revealed 41/194 people (21.1%) assigned to the Venclexta combination regimen had died compared to only 11/97 (11.3%) of those assigned to placebo. This equated to an increase of approximately two-fold in the relative risk of death from Venclexta. The FDA halted the trial on March 6, 2019; however, patients who were experiencing a clinical benefit could elect to continue if they wanted to. The FDA also suspended enrolment in other MM trials involving Venclexta that were ongoing at the time.

However, when researchers performed a subgroup analysis of the MM patients who experienced a clinical benefit, they found two subgroups of patients, those with the t(11;14) translocation and those with high levels of BCL-2, lived significantly longer without disease progression and there was also a non-significant trend towards longer survival.

Translocation is a genetic alteration that is common in MM patients. During translocations, chromosome segments and their genes change positions within the same chromosome or into another chromosome. The t(11;14) translocation means there is a translocation between chromosome 11 and chromosome 14.

Subgroup analysis of people with the t(11;14) translocation or high levels of BCL-2 revealed that 74% had a reduction in their risk of disease progression or death compared to placebo, higher response rates (88% vs. 70%), higher rates of complete response or better (42% vs. 3%), and higher rates of minimal residual disease negativity (19% vs. 0%), as well as a trend toward longer survival.

These findings do support the use of Venclexta in combination with other treatments for relapsed or refractory multiple myeloma bearing the t(11;14) translocation or with high levels of BCL-2. Other trials are currently ongoing.