IMS 2023 | CANOVA: venetoclax plus dexamethasone vs pomalidomide plus dexamethasone in t(11;14) myeloma

The CANOVA trial is a Phase III clinical trial investigating the use of venetoclax and dexamethasone (VenDex) versus pomalidomide and dexamethasone (PomDex) for patients with multiple myeloma who are refractory to lenalidomide. This is a study that kicked off in 2018 but is only reporting its interim analysis now. The reason why it has taken quite a long time to enroll is that we have been specifically looking for the t(11;14) biomarker subgroup of patients, which only encompasses 10-15% of patients, hence it takes a little while to enroll these patients.

The results were presented by Mari-Vi Mateos and essentially demonstrate an improvement in progression-free survival for venetoclax and dex compared to pomalidomide and dex. Whilst numerically there is a substantial improvement in progression-free survival, statistically the primary endpoint was not met. When we look to understand why the primary endpoint was not met, what we find in the flow of the treatment pathway is that more patients in the pomalidomide and dexamethasone arm were withdrawn from the clinical trial without progression. We don’t have full data for that, but what we do know is that some clinicians may have been uncomfortable with patients being on the control arm and withdrawn them earlier compared to the progression. Specifically, we find a disparity between the clinician-reported progression events and the independent review committee-determined progression events, and that accounts for some of the disparity that we are seeing. If we do an adjusted progression-free survival analysis, where we take into consideration when patients are starting next treatment, we then find a statistically significant improvement in progression-free survival for venetoclax-dexamethasone. The overall survival data is still immature but is trending towards an improvement with venetoclax and dexamethasone. And if we look at MRD-negativity rates, there is an improvement with venetoclax and dexamethasone. I think in terms of efficacy, the wealth of data that we have on CANOVA is favoring venetoclax and dex for patients with t(11;14).

Now, from a toxicity profile, what we see is an increased incidence of infection with VenDex compared to PomDex. There were seven deaths with VenDex and no deaths were observed with PomDex, associated with infections. Again, we need to look at prophylaxis and intravenous immunoglobulin to try and limit any significant and fatal infectious events.