ASCT, which has an intensive nature, is performed in subset of patients with MCL. It is clear that, in those who are younger and fitter, such intensive treatment can improve progression-free survival (PFS) compared with standard therapies. The question of whether ASCT improves overall survival (OS) is a topic of ongoing discussion; intensive induction regimens such as R-hyper-CVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab, high-dose methotrexate, and high-dose cytarabine), the NORDIC regimen, and other high-dose cytarabine–containing regimens (with or without early ASCT) have shown improved outcomes as compared with historical controls.

Given that most individuals will progress at some point after ASCT, the issue becomes: How can we prevent or delay post-ASCT relapse while maintaining the patient’s quality of life? The main area where ASCT has been augmented by a maintenance therapy is through the use of rituximab maintenance. This approach is supported by the results of the phase 3 LyMa trial by Le Gouill et al, in which patients with MCL in remission following ASCT received 3 years of rituximab maintenance therapy or observation alone. The study showed that there were benefits in terms of both PFS and OS, and its findings led to rituximab maintenance becoming a standard treatment in this setting. Now, there are novel therapies that have been introduced subsequent to rituximab that are perhaps more effective in MCL, but whether these agents provide similar benefits in the post-ASCT setting as maintenance therapies remains to be seen. At this point, the standard treatment is to administer 3 years of rituximab maintenance following ASCT.

Another question is whether these newer drugs are more effective when used as post-ASCT maintenance or as a retreatment. For example, let us say that you are considering post-ASCT ibrutinib. One has to wonder if it is better to use ibrutinib as post-ASCT maintenance or as treatment when the patient eventually relapses. Generally speaking, rituximab is likely the best-tolerated post-ASCT maintenance therapy that is currently available. And since there is an OS benefit, this approach has been widely adopted. I think that if a kinase inhibitor or some other novel agent demonstrated a benefit when used as post-ASCT maintenance, it would be important to understand the toxicities and the OS and PFS benefits before deciding whether to use that approach.