In February 2026, the U.S. Food and Drug Administration approved an all-oral combination of acalabrutinib and venetoclax for patients with CLL or SLL, marking the first U.S. approval of a BTK inhibitor plus a BCL-2 inhibitor in a pill-only regimen.
The Phase 3 AMPLIFY trial showed improved outcomes over chemoimmunotherapy, with 76.5% of patients progression-free at three years versus 66.5% on standard treatment. Adding obinutuzumab raised this to 83.1%, particularly in high-risk patients.
The regimen is well tolerated and reduces clinic visits since it avoids infusions. Starting with acalabrutinib lowers tumor burden, making venetoclax safer. Treatment is also time-limited to about 14 months, offering deep remissions with fewer long-term side effects, though longer follow-up is still needed.