Dr. Bradley Haverkos, an oncologist at the Anschutz Campus of the University of Colorado, talks about treating rare lymphomas.
Interview conducted by Ivanhoe Broadcast News in 2023.
What is AITL?
Haverkos: AITL it’s also known as Angioimmunoblastic T-cell lymphoma. It’s a type of non- T-cell non-Hodgkin lymphoma. It’s generally an aggressive variant of T-cell lymphoma that we tend to sometimes when it presents with lymphadenopathy and other auto-immune phenomenon. And usually it gets treated with multi-agent cytotoxic chemotherapy.
We’ve heard a lot more about it since Sam Neill from Jurassic Park and other things. Were you surprised that it’s been in the news more now, or is that a good thing for you as a researcher?
Haverkos: Yeah, I think it’s a good thing. It’s a relatively rare subset of non-Hodgkin lymphoma. So T-cell lymphoma is about 10-15% of non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma or AITL, is a subset of T-cell lymphoma. That’s about a third of the aggressive varieties of T-cell lymphoma. So when dwindled down, It’s a relatively rare subset, but one of the more common types of T-cell lymphoma. And so I think it’s always good to bring attention to these more rare diseases because they tend to not respond well to conventional therapies and need better treatments and the better science that can support development of those treatments.
What symptoms might you experience and what is life like is for these patients?
Haverkos: Yeah. So Sam Neill presented right at the right median age of when most people are diagnosed with this. They commonly present with things like fever, chills, night sweats, some weight-loss. Sometimes they’ll present with other other symptoms that are low red cells, anemia, low platelets or thrombocytopenia. Sometimes they’ll present with rash and other wide variety of different types of symptoms. But it’s usually people are fairly symptomatic when they present and then they usually end up coming through the emergency room for a number of these constellation of symptoms, including enlarged lymph nodes as well. So that’s what usually drives them to present the emergency room once they’re diagnosed, usually by a lymph node biopsy. The typical treatment is then conventional cytotoxic chemotherapy.
Is this a particularly aggressive lymphoma. What is the prognosis?
Haverkos: So unfortunately, in general, most people, only around 25% of people are alive at five years after diagnosis. So it’s in a while people do respond to the initial treatment, in general, it tends to come back. And when it comes back there tends to not be very good options to treat it. While we often think about things like clinical trials as a good option for these individuals because the only several approved therapies in the setting once the cancer recurs after that initial therapy. And so we often want to think about other options and better ways to treat this because the standard therapies, in the relapse setting, tend to generally only result in responses around- overall responses of around 30%.
Walgreens just mentioned chemotherapy, obviously. What kind of treatment would you use?
Haverkos: So once someone is diagnosed, they tend to present with a number of different very symptomatic individual with some of the symptoms that I mentioned. So they’d be tend to need to start treatment right away. And the treatment is pretty tough, initially, multi-agent to multiple different conventional chemotherapy drugs that are often used to treat this as a cocktail of drugs. There are several- upfront- several options of cocktails of drugs, some are called chop or epoch or brentuximab plus CHP is a different cocktails of drugs that we use. But in general, they get six cycles of that conventional cytotoxic chemotherapy. And sometimes we think about things like a bone marrow transplant after that initial six rounds of pretty heavy hitting chemotherapy, assuming that the patient is individuals relatively young and fit, we would think about that transplant, but there are many patients that are too old or too frail or have too many medical problems to think about using an autologous transplant.
You mentioned you guys are working on new therapies for when it recurs. What new therapies are working on?
Haverkos: So specifically to the type that Sam Neill had this Angioimmunoblastic T-cell lymphoma sub-type. We know that a portion of those harbor this virus called Epstein-Barr virus or EBV. And so one of the strategies that we’ve been really involved in here is a strategy that uses two drugs that leverages and takes advantage of that virus being there. And so we use this strategy where we make the drugs, the EBV sensitive to another drug. And in doing- and by killing the virus, we can get rid of the lymphoma cells because we think the virus in part drives the cancer. And so we call it this, It’s called this kick and kill strategy. Where two drugs, combination of two different oral drugs that we use. And we recently just publish the data from the phase one trial that we’ve been pretty excited about and are now have a ongoing trial to really hash out how effective this regimen is. And hopefully it’ll be something that we can offer to patients outside of the clinic- outside the context of a trial in the future. But there are other strategies to that we’ve been involved in, but that’s one that’s particularly encouraging for that sub-type of patients.
Are going to look at it’s system? Talking about your research looking at bio-markers that can predict how AITL all patients will respond to therapies.
Haverkos: So one of the- one of the examples of a bio-marker driven, they’re driven approach in Angel-man plastic T-cell lymphoma is by looking to see if that any individual patient harbors that virus to Epstein-Barr virus. And using that as a bio-marker to then treat it with this to drug combination where we can leverage the virus and in doing so in leveraging the virus to treat the cancer. So that’s one example of a bio-marker, different strategy. But there are other examples out there and others that we are looking forward to developing further.
Can you talk to me about any other studies or working related to?
Haverkos: We’ve been real interested in the laboratory so yet in clinical trial, but really interested in laboratory trying to find new drugs to treat this type of T-cell lymphoma or treat different types of T-cell lymphoma. And so we’ve been looking to see if we can find new compounds that may be more effective than the current therapies, or perhaps combining different therapies. And one of the- also one of the ways, in addition to this finding drugs that are more effective at killing the cancer cells by themselves, and also therapies that are less toxic than the current multi-agent chemotherapy regimen. We’re also very interested in see if we can develop ways for that. Your own immune system can fight this cancer as well. And so seeing if there are different drugs out there that can help do so.
What’s the next in your research?
Haverkos: I think the next phase is really some of these newer drugs that we’ve found that are effective against the cancer cells and do a good job of killing them. We want to mainly just explored them in the laboratory and different cell line conditions or mouse model experiments. And we really want to take it to the next level and be able to offer it to patients in the form of a clinical trial. I’ve also been collaborating with our colleagues at Colorado State University because many dogs have T-cell lymphoma. So seeing if that’s an opportunity to weaken further tests, some of these drugs hopefully cure human T-cell lymphoma and dog T-cell lymphoma.
This provides some hope for him, right? It’s a very fast prognosis.
Haverkos: My understanding with Sam Neill is that he went on to get some additional novel more novel therapy besides the after he had failed to conventional therapy. And apparently he’s doing very well. So I think that’s there. While the overall outcome for these patients tends to generally not be good with poor long-term survival or certainly encouraged by some of the trials that we have and some people that benefit really well, benefit for very long periods of time. Some of these trials and also finding within some of the currently approved therapies which patients may benefit most from that therapy. Because we certainly see that some patients can benefit for long periods of time even though the majority may not.
Is there anything else you want to add?
Haverkos: I think gets to your initial comments or questions about, I think it’s really important. This is a rare T-cell- rare type of non-Hodgkin lymphoma that we need to be aware of. And I think it’s important that just bring awareness to this disease and make sure that we’re supporting the science to develop new treatment strategies for this and supporting that research. So I think just echoing what I’ve already said.
END OF INTERVIEW
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