Improving Outcomes in Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 8

Treatment of R/R DLBCL: CD19-Directed Therapy vs CAR T

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John P. Leonard, MD:So Kami, in a world where you have a relapsed large cell lymphoma patient who has not had a good response to second line chemotherapy and is not a great candidate for it, you now might have tafasitamab and lenalidomide as an option and you have CAR T-cells as an option. In the assumption that both are available in a clinical setting, how would you think about approaching those? Clearly and outpatient regimen that's easy to give relatively speaking versus CAR T-cells that are more complex but also for the effective in refractory patients, how do you think about that decision as you would move forward?

Kami Maddocks, MD: As I mentioned regarding the population of patients treated on that trial and as Matt also mentioned that with some other differences, the one downside to the population of patients is they weren’t heavily pretreated. They weren't primary refractory and they weren't double hit patients. We know that those patients do better with CAR T and I would be hesitant to use this combination in somebody who had access to a CAR T center and was in that population of patients that hadn't been studied in this study.

For patients who fit these criteria and both are available, they both have similar responses, similar CR [complete response] and durability is very good with tafa [tafasitamab] len [lenalidomide] also. It's much less toxic, it's much easier to access and it could be given at any center across the country as opposed to sending a patient to a CAR T center. If a patient was not a candidate for CAR T, I would definitely offer the tafa len.I think if it's a patient who had a good response to chemo and is on the board for something, that's a patient I would offer tafa len to if they couldn't get access to a CAR T center. For some of the higher-risk patients, I think we need more information on tafa len and if that really works in those patients like CAR T does.

John P. Leonard, MD:Matt, you alluded to some of these key questions but if tomorrow you had access to one and you have a patient who says they could do either one of these things and would like to try the tafa first, because it's less involved and outpatient and everything else, and do the CAR T if that doesn't work or they relapse. Speaking to the CD19-directed approach, how would you answer that and what would you advise that patient as to the best strategy?

Matthew Lunning, DO: We have an access issue in relapsed refractory large cell lymphoma anyway. I would be thrilled to be part of the discussion about when to use tafa len versus CAR T cell. If it has to be in the Covid-19 era over telehealth, I think that is still worth the time to have laid the roadmap from that because the data is showing us tafasitamab lenalidomide, in the appropriate patient population. It wasn't just a flash one abstract wonder, it's held over time in that patient population. If you’re going to use it first before CAR T cell, there has to be a strategy and you have to be looking to make sure that, just like large cell lymphoma, they are not progressing fast enough. You can't caught on your heels not thinking about CAR T-cell­ therapy right after that. What are you using otherwise, pola-BR [polatuzumab vedotin plus bendamustine/rituximab]? Polatuzumab single-agent or lenalidomide already, ibrutinib maybe?

There is a period of time where you're seeing that you want to go to CAR T-cell [therapy] and you can't or it's going to take long because of logistic reasons. I’ve spoken to this whole mysterious time when you want to do CAR T cell and it's just taking forever to get to apheresis for numerous reasons, tafa len seems to be reasonable, as Dr. Maddocks pointed out, because of the toxicity profile. I'd like to get experience with the drug but to take those patients out of the running for CAR T-cell. If it takes a couple of weeks to get them to their apheresis and then another 3 weeks to get them there, maybe tafa is the best option because it's 8 weekly doses early on. You're getting drug exposure and then you give them the intent to go to CAR or they could say no, and you haven't lost anything if they're responding.

John P. Leonard, MD:Go ahead, Kami.

Kami Maddocks, MD: The one concern people have is just sequencing the CD19 therapy, like Matt touched on a little bit ago, and really does that, using that tafa len as a bridging therapy to CAR T, make the CAR T less effective? We just don't have enough information to say that. There was one patient that's been reported on the L-MIND study that responded to tafa len, progressed after, went on to CAR T and has over a year remission.

But that is an N of one and you can't base anything on one patient. As Matt said, there is preclinical data on treating cells with both the CD19 and that doesn't affect the CAR T effector function. As this becomes available to people, we'll hopefully know more about if there is an effect on the CAR T efficacy.

Matthew Lunning, DO: I think it's important, as we've looked both in the polatuzumab BR coming out and the tafasitamab lenalidomide coming out, that each dose of tafa that's delivered is likely a CAR T-cell patient somewhere in your region. Are you able to and are you having those conversations? Do you have a network established that can say let's work together to decide what the next steps are. And if that next step is tafa len or pola-BR or some other combination therapy that that doesn't include CAR T-cells, so be it. Then we've at least checked that box on the discussion in large cell lymphoma that we should be having with patients out there in this disease state.

John P. Leonard, MD:I just want to ask if there's any data on collecting CAR Ts, having had a patient of mine with mantle cell who recently couldn't get CAR Ts collected because they weren't enough T cells. I know that doesn't come out very often but it’s certainly a consideration. Do we have any data of collecting T cells after lenalidomide? And that might be a good thing. It might be a bad thing. I don't know. Any data on that? Is that an issue?

Matthew Lunning, DO: I have not seen any but I bet you there will be data coming out because of the R2 [lenalidomide (Revlimid) and rituximab] CHOP [cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone] versus CHOP studies that were done. There were patients that were refractory they are. If I had to go back and look at that question, I would key in on that population and see what their outcomes were to second line and how many of them got CAR T-cells. The problem is that they're all going to have gotten another light of therapy that kind of tackles those T cells. It's going to be hard to interpret, unless you're coming off of some of the lenalidomide. There was the Spanish data looking at len plus R-GDP [rituximab plus gemcitabine, dexamethasone, and cisplatin] but that was a transplant ineligible population. The data is out there but it's just kind of just made somebody's ASCO abstract for 2021.

John P. Leonard, MD:There you go. It's out there for whoever wants to tackle that one. There's a study looking at tafasitamab up front. I don't know, Kami, if you’ve been involved in that study or have any insights into that. I don't know if it's open and accruing yet.

Kami Maddocks, MD: There is a phase 1 study open at a small number of centers. We're not involved but it's actually looking at R-CHOP plus tafa and then R-CHOP plus tafa and len. That's ongoing with a planned phase 3 study with R-CHOP and then R-CHOP plus len plus tafa.

Matthew Lunning, DO: I think it's going to be interesting because I've looked at eligibility for that. It does exclude double hits. It does allow I think it's IPI 2 to 5. There are competing randomized trials in the higher risk groups so maybe it's a good thing to have multiple upfront trials going after what cell lymphoma in different groups. Maybe if we do different things, then there will be a positive trial against R-CHOP instead of all negative trials.

Transcript Edited for Clarity