Questions on Frontline or Later Use of Ibrutinib for MCL

Mitchell Smith, MD, PhD, chief medical officer of the Follicular Lymphoma Foundation in Washington, DC, discusses how the updated results of the phase 2 ECOG-ACRIN E1411 trial (NCT01415752) of patients with previously untreated mantle cell lymphoma (MCL) can be interpreted in context of data supporting the use of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica) in this setting.

The ECOG-ACRIN trial investigating the frontline combination of rituximab (Rituxan) plus bendamustine (BR) induction followed by consolidation with rituximab plus lenalidomide (Revlimid) did not show benefit to adding lenalidomide. The SHINE trial (NCT01776840) of ibrutinib, which was started after the other trial, used BR followed by rituximab maintenance as a comparator arm. Based on data from these 2 trials, Smith says that BR plus rituximab maintenance offers 5 or 6 years of progression-free survival (PFS) to many patients.

Though adding ibrutinib was shown to have superior PFS compared with BR with rituximab maintenance, the SHINE trial was not designed to answer whether ibrutinib needs to be given to newly-diagnosed patients or could be given after frontline BR. This could avoid toxicity and costs of the added agent, but the prolonged PFS upfront might be beneficial. Smith says this is an open research question.

TRANSCRIPTION:

0:08 | While this study was going on, there was another…major trial started a little bit after ours and it asked the question about a BTK inhibitor, ibrutinib, which wasn't even around when we designed our trial, but pretty rapidly after, it was shown to be effective in MCL, designed similarly with the BR with the [rituximab] maintenance with the addition of ibrutinib or not, a simple 2 phase. And they found the addition of ibrutinib did prolong the progression-free survival, but their control arm of BR plus [rituximab] was very similar to ours.

So, I think we're getting a feeling that across a number of studies, the basic BR with rituximab for 2 years gives you 5, 6 years. The question in this, what's called the SHINE trial with ibrutinib is whether it is better to have that ibrutinib which you're taking it for 6 or 7 years, or whether you could just get the treatment without the ibrutinib and start the ibrutinib when you progress at year 5 or 6 and get that extra benefit and be saved all the costs and toxicity. That's an open research question that was discussed in the discussion period.