Dr Allan on How Fixed-Duration Regimens Stack Up Against One Another in CLL

“At the end of the day, essentially, what we find when we look at all of these studies is that these are all good regimens. [These regimens] achieve minimal residual disease negativity and debulk patients optimally prior to bringing in venetoclax, making ramp-ups safer.”

John N. Allan, MD, an associate attending physician at NewYork-Presbyterian Hospital and an associate professor of clinical medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medical College, discussed data from a review of currently approved fixed-duration regimens for chronic lymphocytic leukemia (CLL). Allan also discussed the intricacies regarding both safety and efficacy for each regimen based on the data.

The review covered the following regimens: venetoclax (Venclexta) plus obinutuzumab (Gazyva) from the phase 3 CLL14 trial (NCT02242942), ibrutinib (Imbruvica) plus venetoclax from the phase 3 GLOW (NCT03462719) and phase 2 CAPTIVATE (NCT02910583) studies, acalabrutinib (Calquence) plus venetoclax from the phase 3 AMPLIFY study (NCT03836261), and venetoclax plus rituximab [Rituxan] from the phase 3 MURANO study (NCT02005471).

Allan began by highlighting how the review sought to answer questions regarding the best fixed-duration regimens for each patient, how the regimens compare with one another, and why there are different efficacy and toxicity profiles associated with each. Ultimately, each of these regimens are viable treatment options for patients since they all help achieve minimal residual disease negativity, optimally debulk disease, and help make venetoclax ramp-up dosing safer, he said.

However, Allan added that cardiovascular safety improvements were seen with fixed-duration regimens containing second-generation BTK inhibitors like acalabrutinib or zanubrutinib. Moreover, he underscored how, numerically, ibrutinib plus venetoclax might show improvements over other regimens. Allan concluded by pointing out that among regimens that include second-generation BTK inhibitors, he still favors acalabrutinib plus venetoclax, citing how easy the regimen is to use in clinical practice and the significance of the AMPLIFY study that supported its approval.