Emerging data indicate that we are mid-drift away from chemotherapy for the initial treatment of MCL. Unexpectedly positive results with lenalidomide-rituximab (Ruan J. et al. N Engl J Med. 2015 Nov. 5. 73:1835-1844) and ibrutinib-rituximab (Wang M. et al, above) have been presented, and more promising results are emerging. The potential revolution evokes comparison to the recent paradigm shift in CLL. When the HELIOS trial showed that CLL patients lived longer with the addition of ibrutinib to bendamustine-rituximab (BR), some clinicians quipped that the problem with HELIOS was the presence of BR in both arms. The subsequent Alliance A041202 trial corroborated their suspicions, demonstrating that ibrutinib alone was superior to chemoimmunotherapy in older individuals. MCL, however, with its varied presentations and poorly understood biological heterogeneity is not CLL; targeted drugs tend to not work as well, and their failure presages a poor prognosis. Like CLL, some patients with MCL may benefit more from a non-chemotherapy approach. Hopefully, like CLL, the large trials required to prove the concept will be rapidly forthcoming.—Peter Martin, MD