Perhaps, in non-responding lymphomas, BCR pathway activity is less essential for lymphoma cell survival and proliferation, or this pathway is activated by genetic and/or epigenetic mechanisms further downstream, so that upstream inhibition of BTK does not cause a downregulation of this pathway, an example is r/r FL lymphoma with mutation in CARD11 showing poor response to ibrutinib (234). The gene discussed is BCR; the disease is lymphoma.