FDA Approves Acalabrutinib-Venetoclax Combo; Yale Identifies New Leukemia Drug Targets

The FDA approved acalabrutinib (Calquence; AstraZeneca) in combination with venetoclax (Venclexta; AbbVie) for patients with chronic lymphocytic leukemia or small lymphocytic leukemia on February 20, 2026. Acalabrutinib is a Bruton tyrosine kinase inhibitor; venetoclax is a first-in-class BCL-2 inhibitor.

The FDA's decision was based on results from the phase III AMPLIFY study, in which 984 patients received either acalabrutinib and venetoclax or chemotherapy. Median progression-free survival was not estimable in the combination arm and was 47.6 months in the chemotherapy arm; respectively, there were 18 and 42 deaths.

In separate research, a Yale-led study published as the cover story February 10 in Science Signaling found that hyperactive signaling pathways of some aggressive blood cancer cells can be tamped down by a previously unrecognized protein complex, ensuring the cancer's survival. If one component of the complex is deleted or removed, the cancer cells are sent into overdrive and die.

The surface receptor CD25 is one of these components, typically a marker of activated immune cells, but also associated with aggressive cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Detecting CD25 in a patient sample has been known for many years as a sign of poor clinical outcomes.

The study found that leukemia cells express CD25 on the cell surface to assemble a protein complex that dampens activity and makes cancer cells grow at a slower, steadier pace. Most cancers thrive and depend on strong activation signals, which are exploited by therapeutic drugs designed to suppress cancer cell activation. In contrast, leukemia cells in this study were found to depend on a molecular brake to slow down, so their activation levels are just right.

In addition to revealing the previously unrecognized role for CD25 in acute leukemia subpopulations with poor prognosis, the study also highlighted the dependency of tyrosine kinase-driven leukemias on feedback control for their survival.

The Yale-led study sheds light on an unexplored class of new cancer drugs that are being designed to hyperactivate leukemia cell signaling. These drugs that target CD25 and associated proteins can push leukemia cells beyond a maximum threshold of activation that they can tolerate, causing cancer cells to burn out, rather than inhibiting activation signals in cancer.

The Yale researchers examined clinical data from leukemia patients, and implemented genetic modeling that allowed researchers to chart, via mass spectrometry, CD25's interactions with other proteins within the cancer cells in a living organism and to test therapies. The study included collaboration with scientists at Korea University in Seoul, City of Hope Comprehensive Cancer Center, Loma Linda University, University of California San Francisco, University of Pennsylvania, Mayo Clinic, and Montefiore Medical Center.

The research was supported by the National Institutes of Health (awards R35CA197628, R01CA282877, R01CA213138, R01AI164692, R01AI192914, P01CA233412 and R01CA271497), the Arthur H. and Isabel Bunker Chair in Hematology, and Yale University. Additional support was provided by the V Foundation for Cancer Research, Blood Cancer United, the Howard Hughes Medical Institute, All Stars Award, the Rally Foundation for Childhood Cancer, the Leukemia Research Foundation, Alex's Lemonade Stand Foundation, the National Research Foundation of Korea, and by Samsung Research Funding & Incubation Center.