Novel Agents for Treatment of Patients With T-Cell Non-Hodgkin Lymphoma

At the 2022 Lymphoma, Leukemia & Myeloma Congress in New York, Jia Ruan, MD, Weill Cornell Medicine, New York, NY provides an update on new agents for the effective treatment of patients with T-Cell non-Hodgkin lymphoma.

Transcript:

Good morning, I’m Dr. Jia Ruan and I’m a lymphoma physician at Weill Cornell New York Presbyterian Hospital. I’m at the 2022 Lymphoma Myeloma Conference in New York City. Thank you so much for inviting me today to discuss about new agents in T-cell lymphoma. I just gave a talk to summarize what’s new for T-cell non-Hodgkin lymphoma. It’s a very uncommon and quite heterogeneous non-Hodgkin lymphoma. There’s a tremendous unmet need to come up with effective treatments that are of low toxicity.

As you know, a targeted agent has been the objective of pharmaceutical development for T-cell lymphoma. One such example is an anti-CD30 antibody drug conjugate, brentuximab vedotin, which is now approved for systemic anaplastic large cell lymphoma. It has also been approved for use with combination of chemotherapy CHP ([cyclophosphamide, doxorubicin and prednisone]) as an initial therapy for T-cell lymphoma that expresses CD30. It has also been approved for a patient with cutaneous T-cell lymphoma.

There’s quite a few classes of new agents that have great potential. For example, one of them is [phosphoinositide 3-kinase inhibitors] PI3 kinase inhibitors. They come as oral agents and they target the stout form of PI3 kinase, which is very important for T-cell lymphoma pathogenesis. One of the agents that I think it’s quite promising is called duvelisib. It has been approved, actually used in B-cell lymphoma, but its utility in T-cell lymphoma is still being explored. We have phase 1 data which showed a response rate around 50%, with a good portion of complete remission. Now this agent is being studied in the phase 2 pivotal trial, PRIMO. We look forward to getting more information from this study in terms of its effectiveness, and also its side effects profile. Hopefully it would become available to a lot of our patient with relapsed/refractory T-cell lymphoma.

The next class is called epigenetic targeting, so pathways such as histone deacetylase (HDAC), so an acetylase inhibitor, HDAC inhibitor. Examples of that that’s already on the market approved are romidepsin and belinostat. Both of those agents come in intravenous form to be provided in infusion centers for our patients. They’re slightly different in terms of infusion schedules. Romidepsin is once weekly for 3 weeks and then 1 week off. And belinostat is 5 days in a row and it repeats every 3 weeks. I think they, by and large, have very similar effective data. The overall response rate is maybe 25% to 30%. It’s moderate. However, in select population patients, the duration response could be quite durable and prolonged. For example, romidepsin, some of my patient has been on it beyond 2 years, and we know that a proportion of those, a relapsed/refractory PTCL patient, indeed could derive very prolonged benefit with HDAC inhibitors.

There’s an oral form that’s being developed in Asia called chidamide. I think that’s interesting and we’re obviously going to keep monitoring to see what’s new data coming out of there. There’s also methylation modifier, so a hypomethylation agent. There are 2 of them in that category. One of them is azacitidine. It’s a DNA methyltransferase inhibitor. It’s approved for a myeloid disease like [myelodysplastic syndrome] (MDS) or leukemia, but it’s being evaluated now in relapsed/refractory T-cell lymphoma, especially in the form of angioimmunoblastic T-cell lymphoma—they have recurrent mutations that are very susceptible for epigenetic modifications. There’s a global randomized study for a single agent, azacitidine, and we also have a few smaller multicenter study that evaluate the combination of azacitidine with others like romidepsin or even in the firm line settings with CHOP.

I do want to mention that since we talked about PI3 kinase inhibitor, duvelisib, and azacitidine, there is a US intergroup randomized phase 2 study ongoing right now for initial treatment for T-cell lymphomas that are CD30 negative, comparing CHOP plus azacitidine as 1 arm and CHOP plus duvelisib as the other arm, and then comparing that with conventional CHOP. I think it’s going to be very informative and we certainly would encourage our patients and community physicians to consider participating in this randomized study.

The other class I think is of interest is immune checkpoint inhibitor. Its utility is certainly well recognized in other diseases like solid tumors or even B-cell and Hodgkin lymphoma. In T-cell lymphoma it seems to be a very subtype specific, and we’re looking mainly at subtype like NK/T-cell lymphoma, so extra nodal type and be careful not to use it in subtypes, which may actually accelerate the tumor growth. That would be very unwarranted.

In summary, even though T-cell lymphoma is generally rare, it’s very complex. It adds a lot of challenge in terms of coming up with clinical studies and applying individual agents and trying to extrapolate to various subtypes. Now that we have so many new agents in the therapeutic development pipeline, I think the prospect seems to be very promising. We’re very excited for these new agents in T-cell lymphoma.

Source:

Ruan, J. New Agents in T-Cell Lymphoma. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022. New York, NY.