John Gribben, MD, DSc, FRCPath, FMed Sci of Barts Cancer Institute, London, UK discusses the highlights from the second day of the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) 2016 meeting held in San Diego, CA with Anas Younes, MD of Memorial Sloan Kettering Cancer Center, New York, NY, Simon Rule, MD of Plymouth University, Plymouth, UK and Michael Pfreundschuh, MD of Saarland University, Saarbrücken, Germany. First, they discuss the new guidelines for response. Prof. Younes explains the need and rationale for these guidelines, which was due to a lack of clarification in the response assessment in the initial response criteria. The next topic is diffuse large B-cell lymphoma (DLBCL). Dr Pfreundschuh explains the prognostic importance of distinguishing the activated B-cell (ABC) type from the germinal center (GC) cell-of-origin type. Further, he addresses the importance of knowing the subtype and he believes that there will be drugs with a differential effect on the two subtypes; he is not certain whether current drugs such as ibrutinib do indeed have a differential effect as suggested by some results. He further addresses the issue that to date, it has been difficult to know if one is dealing with an ABC or GC type; with NanoString technology, however, there is a now new method available. Prof. Gribben then brings up the next topic of discussion: epigenetic dysregulation in the two major subtypes. Prof. Younes, explains that we have learned that a single genetic alteration may not predict response to certain therapy and that there is genetic cooperation; there is an ongoing trial with HDAC inhibitors selecting for CREBBP mutations (NCT02282358) and the next step may be to combine it with a drug like venetoclax. Next, they discuss mantle cell lymphoma (MCL). Prof. Rule explains that the treatment algorithm is rapidly evolving with the impact of BTK inhibitors and the question is how to manage patients in the long-term and how to sequence therapies. He further mentions that we should not forget about traditional approaches like allogeneic bone marrow transplantation, which still has a role in treatment. The next question is how to manage patients with ibrutinib. Prof. Rule explains that he has a trial of ibrutinib with GA101 (obinutuzumab) coming up (NCT02558816) and if that is going to be a game changer, the next question is duration of therapy and further, the use of molecular monitoring and minimal residual disease (MRD) negativity. Prof. Gribben then asks about the heterogeneity of MCL, which is at the clinical level, and the ‘watch and wait’ strategy. Prof. Rule explains that about 30% of patients will be asymptomatic and he further discusses whether there are subgroups at a molecular level and the topic of proliferation. They then discuss novel therapies, in particular IMiDs and their role in the lymphomas. Prof. Gribben mentions the RELEVANCE trial (NCT01476787) and the impressive results for the lenalidomide and rituximab combination in follicular lymphoma. Prof. Rule argues that perhaps in frontline there will be no need for chemotherapy anymore but patients will relapse and therefore, the sequence of treatment is important. Dr Pfreundschuh then discusses the ‘R-squared’ CHOP treatment in DLBCL and that we have to wait for results from the ROBUST trial (NCT02285062). He then talks about CC-122, which could be a novel IMiD with activity across both subtypes in DLBCL. The final topic discussed is ibrutinib and second- and third-generation BTK inhibitors (e.g. TGR-1202).