By Peter Martin, M.D.Data from three pooled clinical trials suggest that, by itself, ibrutinib works to keep mantle cell lymphoma (MCL) at bay for about one year. For reasons that we have previously discussed on this blog, these results are both impressive and discouraging. For people with MCL, ibrutinib is singular in its ability to produce durable remissions with minimal toxicity. Unfortunately, roughly one third of patients do not respond, while all responding patients eventually experience relapse or progression.
Data from the Chen-Kiang laboratory at Weill Cornell Medicine suggested that palbociclib, an oral inhibitor of CDK4/6, could prevent MCL cells from growing and dividing. Moreover, these arrested MCL cells become even more sensitive to the effects of ibrutinib, essentially overcoming some of the more common mechanisms of ibrutinib resistance and laying the groundwork for a clinical trial.
With the support of the National Cancer Institute, doctors at Weill Cornell Medicine, Ohio State University, Washington University, and the University of North Carolina initiated a phase I clinical trial designed to evaluate the safety and activity of ibrutinib plus palbociclib in people with previously treated MCL. I presented the results of the trial at the 2016 Annual Meeting of the American Society of Hematology. The early results of the trial appear promising, with 70% of patients responding including 45% of study patients experiencing a complete response. More interesting is the observation that only one responding patient has experienced lymphoma progression, corroborating the Chen-Kiang laboratory data that the combination might overcome some mechanisms of ibrutinib resistance. So far, the all-oral regimen appears well tolerated, with low blood counts being the primary side effect.
Although these data appear promising, the number of patients treated so far is relatively small and the follow up time is relatively short. A large, multicenter phase II trial is being planned and will likely open in early 2017. Details regarding that study will be available on this blog and clinicaltrials.gov as soon as they become available.
New Developments in Lymphoma 
Why don’t they add another arm adding Lenelunamide to Ibrutinib and Palbociclib after MCL relapse to see which arm gets longer remissions since they already know that Lenelinamide is active in MCL.