VIDEO: New advancements, molecular targets in lymphoma

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify cperla@healio.com if there are concerns regarding accuracy of the transcription.

In the last few years, for the non-Hodgkin lymphoma specifically, there's a great advancement for this disease. However, non-Hodgkin lymphoma is really heterogeneous population or spectrum for disease. Some of these are very indolent and some of these are very aggressive or highly aggressive. For the highly aggressive disease, like a double-hit or diffuse large B-cell lymphoma, the most exciting progress is really with the CAR T-cell therapy and immunotherapy. Currently, there are three FDA-approved CAR T-cell therapy for diffuse large B-cell lymphoma. However, still, there's a great need for this area. If you look at all the studies for these three CAR T-cell therapy, the overall response is around 70%. But more important, the complete response around 40%. And this complete response was quite durable and potentially this patient in complete response can be potentially cured. However, time will tell. On the other side, if you look the flip side, that's 60%, or 50 to 60%, patients either do not respond or they respond and unfortunate relapse of CAR T. So this is one of the great area we need to improve for this disease and that people have been working on this area. And one thing is while the CAR T fails, when the antigen escape, and for that, right now the field is doing dual CAR T. In addition to CD19, we have a dual CAR T, targeted at both CD19 and CD 20, or CD19 plus CD22. In that way, you can enhance the the CAR T activity. So this is one great area. The other exciting things for the non-Hodgkin lymphoma in general is a bispecific T-cell engager or BiTE, and this is really a unique design. The number of trials, phase II trials, which are very promising for people who even fail the CAR T, they can be potentially treated with this type of agent. The response is quite impressive. And also, importantly, the bispecific antibody in general, is very well tolerated. The cytokine release syndrome and the neurotoxicity is much less. And the phase I trial is just presented at ASH and virtual meeting this year, really, really exciting. Four major bispecific antibodies has show very promising result from phase I studies, and phase II studies are ongoing. And we will see how well that impact the bispecfic antibody, not only for diffuse large B-cell lymphoma which also show very exciting result for patients with indolent lymphoma, such as follicular lymphoma. And we'll wait to see. So this is exciting data from the ASH meetings. The other area in this for the B-cell non-Hodgkin lymphoma, particularly in follicular lymphoma, is the EZH2 inhibitors. Right now, we are all using EZH2 inhibitors. As we know, EZH2 mutation is one of the common mutations in follicular lymphoma and diffuse large B-cell lymphoma. The drug was approved by FDA for relapse refractory follicular lymphoma, but the ongoing clinical trials really show, will probably prove, whether it can combine or how can it combine this very active agent with a existing agent to treat follicular lymphoma or indolent lymphoma and aggressive lymphoma, such as a large B-cell lymphoma. The fourth area I see really exciting from the ASH meeting and over the last couple years is BTK inhibitor. And three of them has been approved by US FDA. The number four was approved in China and they are running trials in the US. Probably this will be prove in the near future. In addition, the other class of a BTK inhibitor called non-covalent-binded BTK inhibitors, LOXO-305, so this is a different molecule, a different class molecule, although they target same major target. However, they are different way of binding the BTK. So for patient who has failed other oral BTK inhibitors, this new agent could prove, from phase I trials, already show a promising result that patient can still respond to this class of drug.