Accredited webinar: Bridging gaps in PTLD care
Transcript: PTLD escalation and referral: An MDT approach
Supported by Pierre Fabre
Susan Prockop, MD.
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The stage is yours. –Thank you so much. This topic unfortunately has a little less publication behind it and there are, I would add the caveat before and I'll talk about during, there are many different pathways by which team coordination for referral and treatment of PTLD are managed. And I think the most important thing, and it can be even different based on which solid organ transplant team is primarily managing and referring the patient in terms of their solid organ transplant care. And so I will emphasize that the most important thing is establishing a plan for the patient and for your center and your group of investigators. So, we can go on to the next slide. And so, I think as you've heard, the care of patients with PTLD can involve reduction of immune suppression, initial assessment of the extent of disease, the pathology of disease, as well as what makes sense as initial and potentially planning for subsequent therapy. And so, to achieve this, you need a multidisciplinary care team that is going to include the primary transplant physicians, be it hematopoietic transplant or solid organ transplant. And the timing for which you need in addition a hematologist or oncologist can vary.
You need a pathologist who is integrally in tune with the different modalities available for the patient and understands the implications of different pathologic interpretations of biopsy results. The infectious disease team at least in many institutions is integrally involved in assessing EBV viral load even before identification of PTLD in patients who have EBV viremia. And then your radiologists are incredibly important in terms of gauging response to therapy as well as the extent of disease at onset. And as you've heard through each of the presentations today, I think the response to therapy is so based on PET scan and on Deauville grading for many of these patients that having radiology colleagues who truly understand the implications of these assessments is important, especially given how rapidly the turnaround to subsequent therapy is needed. It's a little different than some other tumors in the oncology space. And then radiation oncology. We can talk a little bit now about the idea that there are some patients who have either disease at a given site or progression of disease at a given site where low-dose radiation can be helpful if it's a site of disease that is imminently dangerous. This can include, we've demonstrated that low-dose radiation can be helpful in the setting of CNS disease as well as nodal disease that's compressing the airway or the liver. And so having radiation oncology colleagues who are attuned to the idea of, sort of, not palliative, it's not end-of-life-type radiation, but specific site radiation to alleviate specific symptoms is important in the management of these patients. And similarly, interventional radiology, as many of the biopsies can be not so straightforward in this patient population.
And so, as mentioned, this sequential treatment of these patients is on a quite tight timeline compared to some patients with lymphoma. You know there are patients with lymphoma where our first disease assessment is after three cycles of therapy. In this instance, as you've heard, the first disease assessment can be after three doses of rituximab or at the 5-week mark. And so, that early alignment of the team to make sure that you have a plan for the next step is critical. And this is also a place where the team can pivot. So, at least in the US, there are some solid organ transplant teams and some hematopoietic transplant teams who will initiate an initial therapy with rituximab but are not going to do the subsequent therapy, and the subsequent therapy requires a referral to oncology. And so, working closely with the transplant team to make sure that that referral happens promptly is pretty important, as well as having whoever is administering the rituximab or the first-line therapy understand the timeline with which we may need to pivot and the elements of assessment that are required to pivot. As you've heard, I think from others, the importance of knowing high-resolution typing even in solid organ transplant recipients if you're considering cellular-based therapies is important and that can take some time to get. At least in the US that can take time to get even approval to do high-resolution typing.
So, you may want to do that even as you're administering a first dose of rituximab. And then, as you've heard, the response assessment timeline, it's early in the setting of PTLD, and then escalation and referral triggers are really with that type of assessment. Next slide please. And so, there are places where we can optimize our multidisciplinary care and interactions. And I think at least in many settings it makes sense to make a patient-specific plan. So, at the time of diagnosis we, at least here at Boston Children's Dana-Farber, will make a patient-specific plan of what the full disease assessment includes, what the reassessment is going to include, that we go ahead and schedule the PET–CT because that can take some time to schedule, especially in younger children who may need anesthesia for those reassessments, and then predefined escalation triggers, as you've heard, have been established and integral to that is the rapidity of path review, the rapidity of radiology review of reassessment and early identification of patients who may need a subspecialist referral for additional multi-agent therapy or cellular therapy. We typically here, one of the processes that we use, especially for patients who are quite sick at the time of diagnosis, is to establish a weekly huddle for the multidisciplinary care team to meet. And then the suggested pathway that I think many teams try to utilize is the idea that initial confirmation of PTLD can happen and then classification of that and then a multidisciplinary team management plan is established with a scheduled response assessment, as I mentioned, going ahead and scheduling imaging, and then an escalation trigger with the idea that you've already identified whether somebody is eligible or going to be eligible for multi-agent chemotherapy if you've started with rituximab alone or whether you're going to have to escalate directly to cellular therapy if it's available. And then going ahead and making specialist referrals if the person or group that is initially treating the patient is not the same team that would be administering multi-agent chemotherapy or cellular therapy. And then this process of going ahead with high-resolution HLA typing for those patients who may need cellular therapy.
And again, I can just emphasize that these teams can look different center to center and frequently do, but they can also look different like here and at MSK where I was previously. Some of the solid organ transplant teams, like the GI team, liver and small intestine, administer rituximab themselves. Our nephrology colleagues refer the patient before administering rituximab and so the referral pattern can be quite different for different teams even within an institution. It's just important that you know what your team structure is and who needs to be involved when. –Thank you very much, Susan. You addressed this point very well. I'm also a nephrologist and we have, kind of, I wouldn't say, expertise competition but sometimes we did probably too much and we should ask maybe more our hematological colleagues. So, I would like to ask Daan's view on this point. Who would be the one responsible for initiation of escalation therapy? –Yeah, I think the oncological treatment is a responsibility of course of the hematology or the oncologist, but I think it should be a multidisciplinary decision. It also depends on patient-related factors. If you have, for example, a patient of 80 years old, you need a geriatric assessment before to see what's feasible in this patient. If it's a 14-year-old, you need discussion with your pediatrician to see dose adaptations and so on. So, I think apart from that it's important that you also need to take into account that if you see in larger series that the reasons of death in PTLD patients are not always PTLD but are several other factors, infections, and that was told by Susan, the infectiology, the rejection. There are so many pitfalls in PTLD compared to immunocompetent patients that actually you really should sit together. But, of course, the oncological treatment is the oncology responsibility, but it's really also the social, professional, financial issues that need to be taken into account because they are a really vulnerable population in every aspect.
Sylvain, the question goes to you. What do you think could be the practical changes that could mostly improve coordination across transplant physicians, hematologists, pathologists, and specialist referral teams, and where do you see the greatest opportunities to optimize PTLD care pathway in the future? –Well, I think that, I'm quite sure that, the best way to give patients with this so rare disease and such a specific disease is to have a national MDT available with the best specialists in the different organs. We have seen for organ transplants, hematology, radiologist, imaging, anatomical pathologist, because we can speak together. It's not so frequent. For example, in France, we do this once every 2 weeks and we have between five to 12 patients. It's not so much to speak about, and probably to avoid making some mistakes, each time there is a decision to take, to go directly to this national MDT. So, at the diagnosis, for the first treatments, because sometime we can help us or just think about making already the high-resolution HLA typing because they do not know this, just to save time. And when the first response is good and we have already decided that the treatment is not necessary but if we need a relapsed/refractory treatment it is important. If there is some doubt in the evaluation of the response it is also very important. And thanks to this national MDT we have more data and we can propose some protocol, new treatment, new options because we know, we have seen in the literature, that in some cases with a specific presentation this treatment could be effective and important.
Yeah, I know it's difficult to build this national entity, but probably it is the best way to help the patients. –Susan, do you have time to respond to one question as a pediatric question or you have to... –Sure. No, sure. –Okay. So, the question we have: what is the recommended treatment for a 12-year-old with PTLD after kidney transplant who has failed reduction of immunosuppressive therapy and rituximab and secondly treatment with rituximab and cyclophosphamide, prednisone? What would you recommend for this boy? –So, I guess the first thing I would say is that we really don't think about treating pediatric EBV PTLD differently or PTLD differently than adults. It's one of the few places that our treatment algorithms and protocols are pretty much the same. While the risks can be different, especially in solid organ transplant if there's discordant viral immunity, the treatment algorithms are really the same. So, this sounds like a patient where we here would escalate to cellular therapy if it's available. –Okay, thank you very much. At this time point I would like to close the webinar because of the time, and I would like to thank all the presenters for being here with us to discuss all these questions and I would like also to thank you for your attention.
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