Authored by Dr. Brian Koffman
The AMPLIFY trial compared fixed-duration acalabrutinib and venetoclax with or without obinutuzumab with no TP53 or 17p deletion to standard chemoimmunotherapy (CIT) for chronic lymphocytic leukemia (CLL). The interim analysis showed a significant improvement in progression-free survival (PFS) and a trend towards improved overall survival (OS).
This encouraging news is hardly surprising, but it is substantial progress. Single-agent continuous use of ibrutinib has long been proven to be superior to CIT. What is truly significant about this press release of the phase 3 trial interim results is that there is now a fixed duration therapy using a combination of a BTK inhibitor (BTKi), acalabrutinib, and a BCL-2 blocker, venetoclax, that has taken a significant step forward in achieving an eventual FDA approval. The potential approval of fixed-duration acalabrutinib and venetoclax with or without obinutuzumab as a frontline therapy offers the exciting option of an all-oral therapy that could provide deep and durable remissions with long periods off treatment.
While we must wait for the actual data, there is reason to be optimistic. The combination of a BTKi and BCL-2 makes good sense.
Read the press release, Fixed-duration Calquence plus venetoclax, with or without obinutuzumab, significantly improved progression-free survival in 1st-line chronic lymphocytic leukaemia in AMPLIFY Phase III trial.
This trial and the similar MAJIC trial, A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (MAJIC), are no longer enrolling.
If you are considering a similar trial, sonrotoclax, a new and not yet approved BCL-2 blocker like venetoclax, is being combined with the approved BTKi zanubrutinib in this active trial: Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL).
This activity suggests that the future for those with CLL could soon include potent fixed-duration all-oral therapies, starting with acalabrutinib and venetoclax, with the possibility of adding an IV antibody and maybe other combinations coming later.
