Moving From Chemotherapy to Chemo-Free Frontline Care in MCL

Michael Wang, MD, reflects on the evolution of mantle cell lymphoma (MCL) treatment and highlights ASH 2025 data on the phase 2 TrAVeRse study evaluating acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive disease. Wang frames the results within a decades-long transition away from intensive chemotherapy, recalling the significant toxicity and treatment-related mortality associated with regimens such as hyper-CVAD. These experiences motivated early efforts to reduce or eliminate chemotherapy by incorporating novel agents with more favorable safety profiles.

Wang traces the field’s progress and how the advent of BTK inhibitors—beginning with ibrutinib and followed by newer-generation agents such as acalabrutinib—marked a turning point by delivering high response rates with oral therapy and substantially less toxicity. The addition of venetoclax further deepened responses, laying the groundwork for combination strategies capable of rivaling, and in some cases surpassing, outcomes historically achieved with chemotherapy.

The TrAVeRse trial confirmed earlier single-center and smaller studies, demonstrating nearly universal overall response rates and complete response rates approaching 80%. These outcomes were consistent across risk groups, reinforcing the robustness of the regimen. Rapid enrollment and reproducibility across centers further support the regimen’s feasibility and generalizability.

Wang emphasizes that these findings illustrate how far the field has advanced, noting that response rates once considered extraordinary are now becoming routine with rational targeted combinations. He views AVR as a clear example of how frontline, chemo-free therapy may offer patients durable disease control with substantially reduced toxicity, positioning such regimens as a new standard of care for treatment-naive MCL.