The FDA has approved acalabrutinib and venetoclax as the first all oral combination for previously untreated CLL patients based on the AMPLIFY trial data.
This approval is great news for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL / SLL) patients who now have the option of two strong oral medications. Both options have different mechanisms of action (MOA) that complement each other and do not increase toxicities. This synergy of MOA, plus the fact that it is a fixed-duration therapy, lowers the likelihood of developing resistance, suggesting it could be used again for patients with late relapses. Limited duration also means more time off treatment, saving money and avoiding side effects for many CLL / SLL patients who are living longer and looking at multiple lines of therapy over their cancer journey.
Much of the rest of the world has already been using the all oral fixed duration combination of ibrutinib and venetoclax with success, but the FDA had safety concerns. Therefore, the combination was not initially approved in the U.S. Acalabrutinib and venetoclax (A+V) is now, as of Feb. 20, 2026, the first and only all oral option that approved in the USA.
The approval was based on the AMPLIFY trial, which demonstrated in a large, randomized controlled phase 3 trial, the fixed duration combination of acalabrutinib and venetoclax +/-obinutuzumab was superior to chemoimmunotherapy (either fludarabine-cyclophosphamide-rituximab [FCR] or bendamustine-rituximab [BR]) in patients with previously untreated CLL without del(17p) or TP53 mutation. Chemoimmunotherapy’s role in CLL should be almost zero going forward.
It is of interest to note that the trial’s combination of acalabrutinib and venetoclax, plus obinutuzumab (AVO), was not mentioned in the approval. More on that later, but for now, let’s celebrate this good news for American CLL / SLL patients.
CLL Society was quoted in the AbbVie press release:
“With the FDA approval of the combination of venetoclax and acalabrutinib for use as a front-line therapy in CLL, patients in the USA now have an all oral, time-limited option that can be important for many in choosing their treatment,” said Dr. Brian Koffman, co-founder and chief medical officer emeritus, CLL Society. “CLL Society is pleased to see the number of choices available for patients growing.”
Further information can be found in press releases issued from Genentech and AstraZeneca, along with the FDA’s official approval announcement.
