General Updates | An update on nodal T-cell lymphoma treatment and novel approaches being explored

In terms of updates in T-cell lymphomas, if we think, first of all, histologically, and I’m going to focus primarily on the nodal T-cell lymphomas, we know that T-cell lymphoma is a heterogeneous diagnosis and that we have, from the nodal perspective, ALCLs, the TFH lymphomas, of which angioimmunoblastic T-cell lymphoma is the most common, and then PTCL-NOS, and that’s the category where if patients have a T-cell lymphoma that doesn’t fall into any other category, falls into that one. And whilst a lot of trials and treatments have been given to all PTCL lymphomas in the same way, so we give the same treatment, I think increasingly we’re recognising that with many of our newer therapies that perhaps they work better in a specific subtype than another. And I think that’s reflected with some of the trials and the trial landscape that is evolving in the T-cell lymphoma field, where we’re not looking at necessarily drugs in all peripheral T-cell lymphomas but in specific subtypes. So for example, there has been in relapsed refractory T-cell lymphoma good phase 2 data with duvelisib which is a PI3 kinase inhibitor and and that is currently being studied in a phase three study randomizing patients with TFH lymphomas in specific between duvelisib and standard of care investigators choice of either gemcitabine or bendamustine. 

So for example on the ALCL front we know that brentuximab works very well for this class of drugs and has been used for for many years now in the frontline setting, but certainly in the UK and Europe outside ALCL we don’t have a standard use of brentuximab BV-CHP for those types of lymphomas. I think there is still a huge unmet need for patients with relapsed/refractory T-cell lymphoma. I think we know that those patients with that diagnosis don’t do as well as those who’ve got a B-cell lymphoma. So there’s still a lot of work to be done, but I think our knowledge of the underlying pathology is helping inform and giving us better potential treatment options in the future.

In terms of potential interesting future drugs for peripheral T-cell lymphoma, I think we’re all excited, hopefully, to see that maybe there will be an increasing number of cellular therapies, which have been very prominent in terms of relapsed and refractory B-cell lymphoma, but there’s always been a concern about targets for T-cell lymphomas with CAR T therapy. But I hope in the future that there are various mechanisms to overcome that and it’ll be interesting to see trials coming up. There have been some preliminary studies, such as CAR-T studies targeting TRBC1, which it’s still very, very early days, but show some promise. I think where we’re seeing a more active trial landscape that’s more developed, if you like, is with the use of targeted inhibitors, whether that be ALK inhibitors in ALCL or inhibitors such as PI3 kinase inhibitors in TFH lymphoma or EZH2 inhibitors in TFH lymphoma as well. So I think it’ll be interesting to see how those develop, whether they can be used initially as a single agent if they do prove to be efficacious, but then also how they can be combined with our standard of care later on.

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