Chemorefractory Diffuse Large B-Cell Lymphoma- is a Cure Possible with Bruton Tyrosine Kinase Inhibitor?

Treatment of chemorefractory diffuse large b-cell lymphoma (DLBCL) is challenging and associated with dismal outcomes. Detectable novel mutations [i.e., MyD88, EZH2, P53 ] inform potential “oncogenic tumor addiction pathways” and may represent important therapeutic window leading to clinical benefit. Here, we present a 46 y-old male with triple hit activated B-cell [ABC] DLBCL refractory to 6 cycles of chemo-immunotherapy [Rituximab- CHOP] and multiple salvage regimens who achieved durable remission with single agent Ibrutinib. Given ongoing BTK side effects, his medication was stopped and he has been in remission for 2 years suggesting clonal eradication and cure. Our case represents “proof of clinical concept” for durable response after salvage BTK therapy in non-germinal center relapsed/chemorefractory DLBCL. More importantly, to date, our case is first demonstrating durable CR after 21 months of ibrutinib discontinuation. In the near future, molecular identification of actionable mutations [i.e MyD88, EZH2, P53 ] may facilitate recognition of chemorefractory DLBCL subgroups and help improve outcomes with adaptive targeted therapy.