DR. SHUSTOV: I think that the idea of consolidative transplant is very heavily debated and discussed at the majority of specialized PTCL meetings. The reason for that is controversial nature of current clinical evidence. In the absence of randomized trials it is very hard to compare prospective phase II trial data to historical controls. You can interpret this in two ways; you might say, well, these are good data, outcome numbers look better than historical controls, and all patients with PTCL should have a consolidative transplant; or you can say, well, I don't have randomized data, and only a randomized study would really tell us whether post-induction consolidative transplant improves survival.
That is why it is such a controversial subject, and we agree that the phase II perspective studies of transplantation are hampered by significant bias; patients who are able and willing to travel to academic centers, were more robust and able to tolerate high dose therapy. They also have chemosensitive disease and that puts them in a completely different category than those you see in populational or retrospective studies, or other historical control trials.
Having said that, when I talk to patients, and I think that this is where I involve patients into treatment decision very heavily, I present them with the data and say that it is not wrong to do or not do the transplant in first CR. I make patients and family a big part of the decision. When they ask me what would give the patient the best chance being in remission five years from today, my answer is transplant, however, the data are not perfect, and the curative potential of autologous transplant in PTCL is not known.
DR. FANALE: So typically here, we would refer most patients on for front-line consolidative autologous stem cell transplant, I think, some exceptions are the ones that Andrei already touched on. If we're seeing a patient who has PTCL-NOS and this patient is the very rare patient who has early stage disease, with really no significant risk factors, that patient, unless there were pathologic features that showed a higher level of aggressiveness as Alison commented on, this patient might be one where we might defer doing the consolidative stem cell transplant for particularly if the patient’s disease entered into remission very quickly, but this still is controversial.
I'm not sure how you practice within each of your centers, but another patient, or where we would potentially defer, is a patient with fairly limited nasal NK/T-cell lymphoma, a patient that we’ve treated, let's say, with the dexamethasone, etoposide, ifosfamide, carboplatin (DeVIC) chemotherapy regimen plus a concomitant high-dose radiation, we typically historically here have deferred doing consolidative stem cell transplant for that patient population.
In terms of what Andrei commented on for when we might consider an ALLO and for a frontline consolidation, here we typically would not. The exception to that rule is that I've had a couple of patients here who have PTCL with a secondary hemophagocytic lymphohistiocytosis syndrome and then, for those patients because the concern is that the autologous stem cell transplant probably wouldn't be enough and for those patients given that they have such a dismal prognosis from the secondary hemophagocytic lymphohistiocytosis, we send those patients on for an ALLO.
DR. MOSKOWITZ: To expand upon early stage extranodal NK/T-cell lymphoma, I agree with Michelle that we wouldn't use an autologous stem cell transplant in first remission. Typically, for patients with localized disease, we recommend 2 cycles of SMILE followed by involved field radiation. Our patients treated with this approach have typically done quite well without needing a transplant.
DR. HORWITZ: That was great. If there are no further comments on upfront therapy, we can move over to relapse setting. When you see a patient at relapse, what are your strategies and how do you approach that patient?
DR. MOSKOWITZ: The first question in my mind when a patient is either not responding to or relapsing following front-line therapy is: what is my ultimate goal? For a patient who is fit and refractory to CHOP or has relapsed after CHOP or autologous stem cell transplant, my ultimate goal would be to try to get them to an ALLO. My choice of treatment following front-line therapy depends upon whether or not we are aiming for an ALLO as well as whether a donor has been identified for the patient.
Usually, if a patient just relapsed following front-line therapy, we are not necessarily ready to proceed quickly to ALLO. This may be because a donor has not yet been identified or because the patients’ eligibility for an ALLO is not clear. In this situation, my choice of treatment would be something that can be continued, potentially for several months, while we get things in place for the transplant. Treatment options in this situation would include the approved single agents for T-cell lymphoma, such as romidepsin, belinostat, pralatrexate, as well as BV (which would be specific for ALCL). In addition, I would consider enrollment on a promising clinical trial. Among these options, my choice of treatment typically depends upon the side effect profile and/or schedule, which is individualized for the patient. The one caveat would be that I typically will aim to use a histone deacetylase inhibitor (HDAC) inhibitor as my first choice for a patient with AITL.
Usually, if a patient just relapsed following front-line therapy, we are not necessarily ready to proceed quickly to ALLO. This may be because a donor has not yet been identified or because the patients’ eligibility for an ALLO is not clear. If my patient has a donor available and we are ready to move quickly to transplant, I would use one of the multi-agent regimens, such as ifosfamide, carboplatin, etoposide (ICE) or cisplatin, cytosine arabinoside, dexamethasone (DHAP), with the aim to try to get them into remission and relatively quickly proceed to transplant. The problem with using one of these types of regimens for everyone in the second-line setting is that the treatment cannot be continued indefinitely due to cumulative toxicity; therefore we need to know that we are ready to proceed to transplant if we are going to use one of the more intense regimens.
DR. HORWITZ: How do the others approach relapse?
DR. FANALE: Generally, a lot of similarities with what Alison discussed. Typically, it's if we're going to be sending the patient on for consideration for ALLO, I think the favor would be to try to use a regimen that has a high CR rate knowing that there is a trend toward improved progression free survival for the patient who enters into CR when compared to those who did not. I think the only slight difference might be just the timing and the selection, so, typically, here, even if the patient doesn't actually have a definite established donor quite yet we'll typically favor a combination type of a treatment approach, so whether or not that would be a platinum-based regimen such as ICE, as Alison mentioned, or gemcitabine-based chemotherapy regimen or similar.
I would generally favor one of those options, usually, over a single-agent therapeutic approach just knowing that the CR rates, generally, with exception of BV for ALCL are, generally, ranging about the 10%–15% range. And then, of course, first priority would be if there is a clinical trial available whether that's with a doublet of targeted agents or with the targeted agent plus chemotherapy in the relapse setting, we would typically favor that approach for a patient being considered for a stem cell transplant, ALLO approach.