EHA2026 Congress: PTLD highlights
Transcript: Tabelecleucel in EBV+ PTLD: EHA2026 insights
Supported by Pierre Fabre
Sylvain Choquet, MD
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
- The ALLELE study is a multi-center phase three studies with only one arm, but in a very rare disease. This is why it could be with not so many patients be of phase three. It concerns patients in relapse or refractory status of PTLD, which are EBV positive. So every patient already have already at least rituximab and depending on the situations with or without chemotherapy with R-CHOP. So in this study, which is still ongoing, we already have 89 patients with 32 after hematopoietic stem cell transplantation and 57 after solid organ transplantation. It was not possible in this study to include CNS localization, central nervous system localizations. Why this study is very important? If we look at the results of the overall survival of EBV-positive PTLD in relapse refractory status before the possibility to use tabelecleucel, we see that the overall survival is around four months after solid organ organ transplantation and less than one month after hematopoietic stem cell transplantation. So clearly at this moment we needed a new treatments and probably tabelecleucel could be this new options in this situations. When we look at all the population included in this studies, overall response rate is around 50%. So it's quite simple to remember.
And when we look at the overall survival at one year, just remember it was less than one month after hematopoietic stem cell transplant, less than four months for solid organ transplant here, for the whole population, it is around 60, 61% still alive at one year. And if we look as a responder, so the 50% of the populations, the overall survival at one year is more than 80%. And the very interesting points is that we have kind of plateau after this results. If we look at the difference between hematopoietic cell transplant and solid organ transplantation, there's few differences. The overall survival is a bit less after hematopoietic stem cell transplantation. But for example, for the responder it is around 76%. So it's very high. And after solid organ transplantation it is more than 88%. So very, very good response that confirms with even better results the preliminary results we have published few years ago about this ongoing studies. So it's very, very encouraging. Practical point of view. Even if we see a very small difference between the two groups inwards of overall survivals, it is still right now, nowadays, the best treatment available in the situation of second line in EBV-positive PTLD. So whatever the situation is, the best choice is to try to find if there is any available lot of a value of tabelecleucel for our patients and if it is the case to use it. Another point which is quite important, that is that if the first lot does not work, if you have progression and if you have time, it is possible to ask if there is another different lot available for your patients. And since to this attitude, you can move from something around 35, 36% of overall response to more than 47, nearly 50% of response if we look at the whole population with one or two or even three different lots. So you increase the chance of response and the chance of overall survival in these patients asking if you have a different lot, the first one does not work.
This point is very important. And for clinicians who works with PTLD, sometimes some people say that polymorphic PTLD could be treated differently from monomorphic PTLD, which is called non-scale lymphoma in the WHO classification of 2022. But in fact the two entities polymorphic could be positive on non-scale lymphoma or monomorphic PTLD positive have to be treated the same way. The last point I was, I would like to point out, is to underline, is that if you have even a partial response is not so bad in this situation. It's very different from what we see in immunocompetent patients because the patient partial response still have a very good overall survival. It's not very clear why, the first possibility is the evaluation of the patient is not so easy. And the second one probably is because you improve the situation and so you pass the patients in a situation in which the immunosuppression is not so high and can moderate and direct the tumor to stay in the same situation of response or events to improve the response with time. So we do not have to think like immunocompetent patient when we work with PTLD and for these patients you just have to reach at least a partial response and to use obviously in second line tabelecleucel, which is still right now the best treatment available in the literature for this patient and the only one who had an authorization, legal authorization, at least in Europe right now. I think it's really important to reassure the clinicians that with this treatment, because sometimes the question is, okay, you have good response, but the patient will relapse. When you really follow the indications on the when to use tabelecleucel, I mean if you have a response, you have to do a second cycle of two injections even if you have a complete response.
And thanks to this, the relapse rate will be very low. It's important because our colleague from Germany has published some real-life data few months ago in the literature showing that the overall response rate is not so bad, but they had around 50% of relapse in the situation, relapse refractory EBV-positive PTLD. And this is not at all what we see in France or in Italy when we follow the indication of second cycle after a very good response. And when we asked our German colleague, they told us that in fact if the complete response was reached after the first cycle, they stopped there. This is not the best way I think, I believe, for this patient, you really have to make a second cycle after or third one if you have only partial response. And thanks to this situation, the relapse rate is very low. When we look at the progression-free survival and the overall survival, we have a kind of plateau after around two years, which is not so bad. It is around 70% for responding patients. In this situation, it's remarkable, because you reach the normal life expectancy of the other transplanted patients who did not have any PTLD. So it's very encouraging new treatments, reaching the target we had before it exists. The safety profile is very important because we are working with very frail patients. Usually they have infections, they have kidney insufficiency or other kind of organ insufficiency. This is the way we deal with transplanted patient.
It's always the same thing. If you look at an overall survival curve of all the transplanted population, it is not with a plateau as they can, in the normal population, but it always decrease with the time. So in this situation, which is quite different from the one we see in the immunocompetent patients, we have to think of safety, much more important than in the immunocompetent patients. Sometimes it's impossible to use chemotherapy because the patient is to fragile, and especially after hematopoietic stem cell transplantation. So we look very carefully to the safety profile and in the study it is quite difficult to analyze clearly the results. But if you look only at the severe adverse events since grade three and more adverse events related to tabelecleucels, the level is quite low. We didn't see any complex rejection of the organ. We have some rejections but with a very easy deal and way to treat them. And only if I will remember two case of grade one GVH disease. So it's very simple to deal with, no infections due to tabelecleucel. But probably the most important thing is the real-life use of tabelecleucel. In our unit on the, in the other unit who had the opportunity to use tabelecleucel, it is really easy. We see nearly zero side effects in the very frail patients.
It is possible to use it in outpatient basis and clearly even is the personal status, the ECOG status is three or four. For me, it's not a contraindication to use tabelecleucel because the patient will not have any or very few side effect. If we have very good results with these new treatments, there is two unmet, important targets. The first one is probably we can improve the results of tabcells beginning very early in the treatment of PTLD, even even in the first line when tabelecleucel is not indicated. But thinking about the 30 to 40% of patients who will not respond to first line, to take time very early to make the HLA typing of the donor if you do not have it. And sometimes it's very difficult to find in the files of these patients, of the donor when it was done 10, 20, 30 years ago and sometimes at least once in our unit, we had to make a biopsy of the, of the transplant in lung because it was impossible to find the HLA of the donor. This take times and even if you have to come back to the medical files of the patients, it can also take times, and if you want to save your times and to save, to give more chance of efficacy with tabcell is to have already the data of the patient HLR and the donor HLR and to make the maximal chance to have also the origins of the tumor. Because at this time it'll be very quick to have an answer from a PFS laboratories to know if there is an available lot on you. So this time saving could be very important and probably could improve the response rates and the overall survival and PFS curves of stem cells. This is the first point, but also we know that this new treatment is not available, is not available for every patient because some populations, for example, Japanese people, do not have much chance right now to have compatible lots. For Europe it's around 90%, but for other population this is also a new target for the lab.
And even with more valuable for the patients, it will not work for all patients. So we still have to find new treatments for patient with EBV-positive PTLD after failure or without any available tabcells, tabelecleucels for stems. So new treatments are still important and just remember that for adult people about 50% of PTLD are not EBV-positive and so we do not have the possibility to use tabcells. And in this populations, which represents 30 to 40% of all PTLD and the second lines, we really need new treatments. Right now we use the treatment we know for immunocompetent patients, but sometimes they are too aggressive and to toxic. For example, CAR-T cells very difficult to use in immunosuppressed patients and the results are far less interesting but still interesting bits in the transplanted patient in comparison with immunocompetent patients. So we have still a lot of work to do in the field of PTLD, EBV-positive or EBV-negative, and probably the physiopathological treatments using EBV as a target could be interesting. There is some work resembling EBV, EV types with kind of CAR-T cells, why not? But also for the other with negative PTLD, we have a lot of work in the future for these patients.
Developed by EPG Health for Medthority. This content has been developed independently of the sponsor, Pierre Fabre, which has had no editorial input into the content. EPG Health received unrestricted educational funding from the sponsor in order to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content. This content is intended for healthcare professionals only.
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