Medical Roundtable: Peripheral T-Cell Lymphomas: A Practical Approach to Newly Diagnosed and Relapsed Patients

DR. SHUSTOV: I share your frustration with quite a few of the current study designs for that exact reason. Some of these are confirmatory trials after conditional approvals of the new agents and are important. However, as often happens, in the confirmatory trials, we use controls that are a default from a lot of historical data, or the “common” way that the majority of patients are being treated. It is really a challenge when you consent patients to studies where a control arm is something that you think might not be quite adequate.

Having said that, the CHOEP study that was mentioned several times is a retrospective subgroup analysis and the addition of etoposide had marginal benefit that approached significance, but certainly was not a home run. I don't think we are ready to say that etoposide provides survival advantage in T-cell lymphoma patients and dismiss clinical trials in favor of just giving a patient the CHOEP, even though CHOP is admittedly not the best comparator. I discuss this controversy with patients and tell them frankly that the data that we base addition of etoposide on are not the best evidence one may have. Then, I ask patients to decide which approach sounds more reasonable to them and they make their choice.

DR. FANALE: To expand just slightly upon what Andrei said, I do emphasize to the patient and to the referring doctors that if you look at National Comprehensive Cancer Network guidelines, CHOP, CHOEP, EPOCH, all of these are potential options. So there's really not yet one trial that would say that one is clearly superior to the other at this time. I also emphasize to the patient and to the referring clinician that the only way, let's say, the patient could get the targeted agent plus the chemotherapy and have that 50% chance of, potentially, receiving that combination is really through the randomized clinical trial.

DR. HORWITZ: That was excellent, thank you. So you have alluded to this a bit. How much does subtype specific treatment come into play?

DR. MOSKOWITZ: At this point in time, outside of a clinical trial, for PTCL-NOS, AITL, and ALCL, the front-line approach would typically be CHOEP followed by autologous stem cell transplant. As Michelle mentioned, for a patient with ALCL, I would offer enrollment on the ECHELON-2 study in which patients are randomized to CHOP or BV-CHP, in order to give patients the option of potentially receiving BV.

For AITL, we are now obtaining molecular testing for certain mutations, particularly IDH2, because we currently have a study open with an IDH2 inhibitor that specifically enrolls patients with IDH2-mutant AITL. Because the testing takes some time to get back, we typically test patients’ biopsies at the time of diagnosis, so that we know if they're eligible for future clinical trials in case their disease does not respond to upfront therapy.

There are T-cell lymphoma subtypes that we treat quite differently from the entities discussed so far. For human T-lymphotropic virus-1 associated adult T-cell lymphoma, for example, the data with CHOP are really not good and we typically used EPOCH with the aim to consolidate with an allogeneic stem cell transplant.

Likewise, for hepatosplenic T-cell lymphoma, we have not observed good responses with the CHOP-based therapy and therefore we typically use platinum-based or ifosfamide-based therapy upfront with the aim to consolidate with allogeneic stem cell transplant. Extranodal NK/T-cell lymphoma is another entity for which CHOP is typically not effective and we have adopted asparaginase-based regimens, such as dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide (SMILE) for this disease.

DR. SHUSTOV: I completely agree with Alison; for more common nodal lymphomas it is really hard at this point to base a treatment decision on histology, at least, in the front-line setting. However, some of the rare and unique subtypes, we generally treat with a completely different approach (ie, extranodal NK-cell lymphomas, enteropathy-associated T-cell lymphomas, adult T-cell leukemia/lymphomas).

DR. HORWITZ: Excellent. I’m curious, in a patient with ALCL who refused randomization of the ECHELON-2 trial, would you give them BV-CHP off study or would you discuss that as an alternative were they not to participate in the trial?

DR. FANALE: No. I don't urge treatment that's not approved for a particular line of therapy off clinical protocol with the exception that, let's say, if a patient is not a candidate for chemotherapy in second line setting for a particular lymphoma such as Hodgkin lymphoma—then, I would reference published data like Alison's data for a second line use of BV say for classical Hodgkin lymphoma and work with the insurance company to get the drug approved for that patient population, but if a patient just doesn't want to go on trial because they don't like the 50/50 chance of receiving BV-CHP compared to CHOP and they say, “I really want the 100% chance. Why don't you just contact my insurance?” I will explain to them the rationale of why the trial is being conducted including the hope that if the endpoints are met and the regimen is approved for front-line therapy then patients in the future can get BV-CHP at any oncology clinic, but I tell them for now it is a protocol based treatment option.

DR. HORWITZ: That's a very good answer. Can we now touch on the idea of transplant vs no transplant in first remission. Always, sometimes, never; how do you all think about that?