Future Directions in Relapsed and Refractory Large B-cell Lymphoma

Summary

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Blood Podcast: Future Directions in Relapsed and Refractory Large B-cell Lymphoma

American Society of Hematology | June 11, 2026

Episode Overview

This bonus episode of the Blood Podcast features Associate Editor Dr. Philippe Armand in conversation with Dr. Manali Kamdar and Dr. Nancy Bartlett, authors of a comprehensive review on the evolving treatment landscape for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). The discussion centers on new clinical trial data, practical treatment decision-making, regulatory changes, the impact of emerging therapies, and future directions for research and patient care.

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Key Discussion Points & Insights

1. Current Approach to Relapsed/Refractory DLBCL (01:12–03:23)

• Initial Assessment: Dr. Bartlett discusses considering patient age, performance status, prior therapies, and social factors in treatment planning.
  • “Age, performance status, and in terms of the performance status, it really depends on whether it’s sort of baseline comorbidities or...because of the disease...Other questions are what therapy or therapies they've already had and some social issues...” (Dr. Bartlett, 01:13)
• CAR T-cell Therapy as 2nd Line:
  • For patients suited for second-line treatment, CAR T-cell therapy is prioritized due to its survival and curative advantage.
  • If not a candidate for CAR T, options include bispecific antibodies, antibody-drug conjugates, or standard chemotherapy. Combination regimens (e.g., Glofitamab plus Gemox, mosunetuzumab with polatuzumab) are increasingly considered.

2. Recent Trial Data’s Impact on Clinical Decisions (03:23–05:56)

• Shift from R-GemOx: New data demonstrating superior outcomes for regimens like polatuzumab plus GemOx or mosunetuzumab plus polatuzumab may make R-GemOx obsolete.
  • “Probably R-GemOx is going to be a thing of the past.” (Dr. Kamdar, 04:28)
• Bispecific-anchored Therapy: Especially appealing for off-the-shelf use in cases of rapid disease progression; can serve as bridge to CAR T or as standalone therapy in select patients.
  • “Amongst all the new clinical trials that have panned out some positive results, I am most impressed with the bispecific anchored therapy like Starglo...” (Dr. Kamdar, 04:49)

3. Role of Bridging Therapies Before CAR T (05:56–09:21)

• Bridging vs. Holding Therapy:
  • Bispecifics and new regimens are often used as bridging while awaiting CAR T manufacturing, especially for patients with aggressive disease unresponsive to local control or standard chemotherapies.
  • Concerns exist about T-cell milieu alteration if bispecifics used pre-apheresis, potentially affecting CAR T product quality.
  • “Are we going to have enough T-cell health to collect CARs…Sometimes you're just stuck between a rock and a hard place. My preference would be to choose the most effective holding instead of something that's 100% guaranteed that it's not going to affect the collection.” (Dr. Bartlett, 08:16)
• Real-world Dilemmas: Long waits (often for insurance) force clinicians to balance disease control with preservation of future CAR T eligibility, often without solid evidence to guide choices.

4. Incorporation into Auto-Transplant Pathways (09:21–11:10)

• Evolving Approach: Increasing use of bispecific antibody regimens as pre-auto stem cell transplant rescue. Experience suggests these regimens do not compromise subsequent CAR T collection.
  • “We had no problem collecting CARs in any of those patients who were participating in that trial.” (Dr. Bartlett, 10:08)
• Trial Examples: Use of Glofitamab or other bispecifics plus chemo in both pre-transplant and pre-CAR T settings.

5. Exciting Ongoing & Future Trials (11:10–13:31)

• Frontline Trials:
  • Trials combining bispecifics with chemo (e.g., Skyglo, EPCOR phase 3) may redefine first-line standards if positive endpoints are reported.
    • “I’m…looking forward to see the results of the frontline bispecific plus chemo studies…patients have had exceptional responses.” (Dr. Kamdar, 12:03)
• CAR T Innovations:
  • CD19 vs. CD19/20 dual-targeted CARs under investigation.
  • Allogeneic/off-the-shelf CARs may expand access.
• Novel Agents:
  • BCL6 degraders identified as particularly promising: “It knocked my socks off when I saw how heavily pretreated these patients were and…achieved a complete response of 11%.” (Dr. Kamdar, 13:19)

6. Anticipating Effects of Changing Frontline Therapy on Relapsed/Refractory Patterns (13:31–15:40)

• Therapeutic Sequencing Complexity:
  • As frontline regimens incorporate more advanced agents, relapse scenarios become less predictable—necessitating nuanced retreatment decisions (i.e., reusing or rotating targeted drugs).
  • “We can't just lay out a plan—here's A, B, C, D in this order—because I think that's gonna get mixed up when we see some of the results of the frontline.” (Dr. Bartlett, 14:57)

7. Challenges in Clinical Trial Design & Implementation (15:40–23:04)

• Access and Equity:
  • Significant disparities in trial access for various demographics and medical settings.
  • Ensuring broader participation outside academic centers critical for generalizability.
    • “I think...access to these new immunotherapies...is going to be of paramount importance to serve the population they do.” (Dr. Kamdar, 16:12)
• Community Setting Deployment:
  • CAR T and bispecifics are challenging to administer outside major centers, posing practical and safety considerations.
  • Training and collaboration essential for expanding access.
• Toxicity Management & Trial Duration:
  • Concern over chronic infections/toxicities with long-duration bispecific antibody regimens.
  • Over-extended treatment durations driven by non-clinical motivations.
    • “I'm not sure how long it would take someone...to diagnose those kind of oddball things that happen. And so...another issue I have with trial design is just...how long these treatments need to go on...” (Dr. Bartlett, 19:27)
• Selective Enrollment:
  • Exclusion of CNS lymphoma patients highlighted as a major limitation in current studies.

8. Potential Breakthroughs on the Horizon (23:04–24:17)

• Allogeneic CAR T:
  • Early outpatient trial experience in MRD-positive first-line setting shows remarkable safety (minimal CRS/ICANS), suggesting route for broader adoption.
  • “They have potentially no or very little CRS or ICANS. That seems much more amenable to being used in any setting almost.” (Dr. Bartlett, 24:03)
• Regulatory and Real-world Evidence Needs:
  • More adaptive and de-escalation trials necessary for optimizing regimens post-approval.

9. Final Thoughts (24:17–24:46)

• The relapsed/refractory DLBCL space is changing rapidly, driven by successive approvals and expanding therapeutic classes.

• Key priorities: rational trial design and a relentless focus on access, equity, and meaningful patient outcomes.

  • “It’s really important for us to make sure that we design biologically rational studies, but also make sure that access is improved so that all patients can...enjoy the benefits of these amazing constructs.” (Dr. Kamdar, 24:22)

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Notable Quotes (with Timestamps)

• "Probably R-GemOx is going to be a thing of the past."
  — Dr. Manali Kamdar [04:28]
• "Sometimes you’re just stuck between a rock and a hard place. My preference would be to choose the most effective holding instead of something that’s 100% guaranteed that it’s not going to affect the [CAR T] collection."
  — Dr. Nancy Bartlett [08:16]
• "We can’t just lay out a plan—here’s A, B, C, D in this order—because I think that’s gonna get mixed up when we see some of the results of the frontline."
  — Dr. Nancy Bartlett [14:57]
• "I think...access to these new immunotherapies...is going to be of paramount importance to serve the population they do."
  — Dr. Manali Kamdar [16:12]
• "It knocked my socks off when I saw how heavily pretreated these patients were and...achieved a complete response of 11%."
  — Dr. Manali Kamdar, on the BCL6 degrader [13:19]

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Important Timestamps

• 01:12 – Dr. Bartlett’s practical approach to relapsed DLBCL
• 03:23 – Dr. Kamdar on recent trial data and shifting standard practices
• 05:56 – Use of bispecifics as bridging or holding prior to CAR T
• 09:45 – Integrating new therapies into the auto stem cell transplant pathway
• 11:22 – Most anticipated trials poised to impact future standards
• 13:59 – Challenges in retreatment after more complex frontline regimens
• 16:05 – Clinical trial access and representation issues
• 19:08 – Toxicity management and treatment duration concerns
• 23:04 – Allogeneic CARs and next-generation outpatient regimens
• 24:21 – Final thoughts on rational trial design and equitable access

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Summary

This episode offers a richly detailed overview of one of hematology’s most dynamic and challenging areas. The conversation underscores how advances in immunotherapy—CAR T-cells, bispecific antibodies, ADCs, and novel molecular targeted agents—are upending standard approaches to relapsed and refractory DLBCL. Both Dr. Kamdar and Dr. Bartlett expertly contextualize recent trial data, practical dilemmas, and future research goals, emphasizing the critical importance of access, flexibility in clinical trial design, and adapting to a fluid, rapidly evolving therapeutic landscape. This is essential listening for clinicians and researchers seeking to keep pace with and contribute to the next breakthroughs in DLBCL care.

Transcript

[A]

Welcome to this week's bonus episode of the Blood Podcast, your source for innovative ideas and cutting edge information. In this episode, Associate Editor Dr. Philippe Armand discusses the review entitled Breakthroughs to Evolving Evidence and Future in Relapsed and Refractory Large B Cell lymphoma with authors Dr. Manali Kamdar and and Dr. Nancy Bartlett.

[B]

Hello everyone and welcome to this blog podcast. I'm delighted to have two fantastic speakers today, Dr. Kamdar and Dr. Bartlett, who wrote an outstanding review on the trial landscape for relapsed refractory diffuse large B cell lymphoma. This is a field that's becoming increasingly confusing for both clinicians and researchers. So I'm delighted that you're here today and that we can get your insights on this rapidly moving field.

[C]

Thank you for the invitation.

[D]

Thank you.

[B]

I'm going to start with you, Dr. Bartlett, and ask you to quickly summarize where we're at now, meaning when you see a patient in clinic, of course there are lots of subtleties, but in the general outline, how do you approach the treatment of someone with relapsed olfactory dlbcl?

[D]

Today, when I see a new patient, there's lots of patient characteristics and disease characteristics that are obviously going to affect my thought process in terms of deciding on a therapy. But I think age, performance status, and in terms of the performance status, it really depends on whether it's sort of baseline comorbidities or it's a bad performance status or poor performance status because of the disease, in which case that affects me less because the hope is that they're going to respond to the treatment and their performance status will improve. Other questions are what therapy or therapies they've already had and some social issues in terms of how far away they live and do I think they're going to be compliant. And those are really the main things. And then in terms of my thought process about what the options are, I think given the current data for CAR T cell therapy showing a survival advantage, if it's second line therapy, then I would be assessing them to see whether they seem like an appropriate candidate for that because it is still the treatment that has the highest chance of curing the patient. And so that would be sort of number one on the list. And if it's very clear that there's something about their circumstances, whether it be other medical problems or no support or that sort of thing, that they're just not going to be able to carry that form forward than thinking about second line treatments, should it be something mild if they're quite debilitated. Or could they potentially participate obviously in a clinical study? We have a lot of clinical studies ongoing looking at bispecific antibodies and newer cars. But probably in that situation I would be looking at if I did not think that they were a car candidate or a transplant candidate, I would be thinking about probably a combination of a bispecific plus either antibody drug conjugate or standard chemotherapy. First things coming to mind would be Glofit, Gemox, Mosipola, things in that category.

[B]

Thank you very much. And Dr. Kumda, I'm thinking because you guys reviewed very well the recent trials that have shown some at least progression free survival benefit in many cases over Argemox therapy. How does that factor into your treatment? Now if you think that the baseline is rapid, relapse goes to car, later relapse goes to salvage and auto for patients who are candidates for both. Have the recent data impacted your clinical practice?

[C]

I think it has in terms of just the ability to get somebody started sooner. Especially when we talk about ADC anchored therapy. Based on the Polargo study, our Polatuzumab plus Gemox was superior in their primary endpoints compared to our Gemox. The same goes with Sunmo where ADC was combined with a Bispecific where Mozinpola was better than Rgemox. I think it's quite important to underline that probably Rgemox is going to be a thing of the past. And the big question is what do we treat our patients when the cadence of the disease is proliferative enough, where an off the shelf treatment is going to be more valuable and than something like CAR T where it takes time to manufacture whether it's in patients who are fit or unfit. I think amongst all the new clinical trials that have panned out some positive results, I am most impressed with the bispecific anchored therapy like Starglo where there was superiority in the endpoints for Glofid Gemox versus Gemox alone. I think in a patient with who has relapsed diffused large B cell lymphoma, especially if they have seen Polatuzumab in the frontline setting and have relapsed within a year. They're primary refractory and I would deem them say for example not to be car eligible. I think something that is Starglo regimen, GloFit plus Gemox would come to my mind because it would be off the shelf. It still doesn't take away their chances to get Karthi in third line, especially some of the PFS curves of these clinical trials are quite impressive. They're matching up to CAR T. There's never been a head to head study between bispecs and cars and I doubt that will ever be done. But I think that's how I'm looking forward towards implementing some of the new data with bispecifics with chemo or bispecifics with ADC into clinical practice. Because thanks to the NCCN guidelines, even if they are not FDA approved yet, they are now in the NCCN guidelines.

[B]

Thank you. So if I may push you a little bit on this. If you have a patient who is a CAR T candidate, would you use those therapies instead of CAR T as bridging therapy?

[C]

I think that is a very relevant question. In our day to day clinical practice, each one of us is actually seeing patients where I think for me a randomized phase three study that compares the previous standard of care which is autotransplant matters, a cure that has been demonstrated with the five year followup matters. And we do know that in the second line study for the appropriately selected high risk second line DLBCL patients, primary refractory early relapsing settings, 50 to 55% of patients will be cured. I don't think we have that kind of follow up with any of the bispecific treatments. But what this allows us to do is as soon as a referral is placed, I am doing everything to get my patient in to see them in clinic, get them a spot in apheresis. But after apheresis, if the disease cadence is such that just radiation therapy is not going to keep a local bulky disease under control, that's when I'm going to pull in my GloFits and Epcos to hopefully rapid ramp them up to keep their disease stable and then eventually get them to cars when the manufacturing is done. And I would love to ask this question back to both of you. I kind of don't know. I've never quite used bispec as a holding therapy prior to apheresis. I've used it a lot as bridging, but prior to apheresis I don't know if the T cell milieu that I change will actually impact the Car T product.

[B]

Thank you Dr. Bartlett. I don't know if you want to comment on that.

[D]

Yeah, I would. I think we're all worried about that. Just as Manali said, are we going to have enough T Cell health to collect cars. And I know our car T group is concerned about that. But sometimes, and I have had these patients, I mean there's not another gentle bridging for someone who has very bulky rapidly progressing disease. So when you know you have something like Glofit Gemox and I will say I've gotten away with it, that I can't remember a patient where I had bispecifics given as holding as opposed to bridging. And because sometimes you can't get the car spot and for us it's usually an insurance holdup but it can be 8 weeks or 10 weeks or longer and that's holding somebody with some steroids or they need something and I mean you could just give the Gemox but we know that's pretty ineffective because we now have the advantage of having all these trials comparing all the new therapies to our Gemox and it's computer consistently poor performing. I generally say we don't have a choice and I think they need the most effective therapy while they're waiting so that they don't die and never get to car. And although it wouldn't be their first choice, but they're also understanding that. So I would like to see more hard data. Maybe this is where we can find some real world data if institutions have been doing some of this. And again I think sometimes you're just stuck between a rock and a hard place. And my preference would be to choose the most effective holding instead of something that's 100% guaranteed that it's not going to affect the collection.

[B]

Dr. Bartlett, another question for you. We've talked a lot about car and whether this is appropriate before car maybe someday instead of car. What about the other side of the one year relapse? When we treat patients currently with salvage and auto transplant who are candidates for auto transplant. Have you incorporated these therapies to get patients to auto and if so, which do you use?

[D]

We have slipped away from auto but interestingly we actually had a clinical trial ongoing here with Mohsen and then physician choice between ice and DACs and at first I was a bit nervous about that because that was supposed to be pre auto that they were going on for that and then if they'd have a couple of cycles and they wouldn't respond, we would actually just pivot and go to car T and those are some of the patients I'm talking about. We had no problem collecting cars in any of those patients who were participating in that trial. I also think now that we know What Gemox provides for us, which is very little that I think using bispecific plus chemotherapy and, and up until the approval for Glofit Gemox we didn't even have that option. So we were doing it as part of a trial here. But I think that giving a bispecific plus chemotherapy and will be helpful. I think as Manali and I reviewed in the paper, there's a few other things out there using I think Glofit ice or Apco ice and this sort of more aggressive chemotherapy to go on to a transplant. But even going on to cars we've had a lot of luck with. If they don't respond then you don't want to just go on to transplant because that's not going to have a happy ending. But again, I think we haven't had any problem going on to CAR instead.

[B]

Great. Thank you both. And looking at the future, Dr. Kamdao, what ongoing trials are you particularly excited about that you think might change change the standard of care in the next few years?

[C]

Right now in clinical practice for Frontline we use rituximab plus chemo with without polar in the second line setting. For the appropriate patients we are going to car, majority of them are high risk relapses and then after that we are typically going with CD20 bispecific T cell engages obviously for the relapsedrefractory cohort. Beyond that there are the long cuties and the Tapha lens. Based on expression, I think I'm most curious to see and very much looking forward to see the results of the frontline bispecific plus chemo studies, Dr. Bartlett has participated in those as well. And in the recent Skyglo study or The EPCOR Phase 3 study, at least the ones that were open at my site, patients have had exceptional responses. So if they these studies truly translate into an endpoint benefit and become the standard of care, I do believe the second line setting becomes still open and then the third line setting continues to be open, then the second line setting. I'm looking forward to the car versus car studies where CD19 FDA approved cars are compared to CD19 20 cars. A lot of these clinical trials actually are barring transplant fitness because I think everybody realizes that transplant eligibility doesn't necessarily translate into CAR T eligibility. Patients who are CAR T eligible may not be transplant eligible. And in the third line setting I'm looking forward to studies such as the roll one studies because they are technically antigen agnostic. I'm looking Forward to the CD19 bispecific T cell engages the surovatomic data that is coming out and But I will say I think the most promising agent this ash was the BCL6 degrader. I think it knocked my socks off when I saw how heavily pretreated these patients were and in that setting they achieved a complete response of 11%. I always thought that the BCL6 degrader would have to be combined with an agent, but it seems like it's less toxic in and itself a single agent is quite promising and I'm looking forward to developing those those constructs ahead.

[B]

Great, thank you. And that actually you touched on what was going to be my next question for maybe for Dr. Bartlett is there's so many changes afoot in frontline therapy where the bulk of the phase three action is now in dlbcl with many trials that are likely to read out in the next few years and could significantly affect standard of care. How do you think this is going to leave patients with relapse, olfactory disease and where is it going to leave us as clinicians in terms of choosing therapy in second line and beyond?

[D]

That's a great question and I think Manali and I struggled with that when we were writing the review. In terms of how to express that as a difficult part of outlining the treatment for relapsed DLBCL when the front line could change and is including some of the agents that we're looking at for relapse. I think it's going to be sort of those age old questions in terms of can you reuse drugs that you've already used and it's going to depend on how long the remission was. Sort of the same question we're facing in relapsed Hodgkin's with PD1 inhibitors. If they already had it, can you, should you use it again? I think it'll be the same thing with the bispecifics in terms of whether you can use it again. And if not, then we'll be looking at the alternates that they didn't get as frontline therapy. I mean even looking at the polar chip, that's already hard to figure out. You know, a study like Polargon, which is Polatuzumab and Gemox, that's only going to be useful if you relapsed sort of pre pola days, if you will, because so many of the patients are getting it as frontline. And again it'll depend on how long ago it was. Could you use it Again, so those are going to confuse us even more in terms of. And that's why we can't just lay out a plan. Here's A, B, C, D in this order. Because I think that's gonna get mixed up when we see some of the results of the frontline. And I know they're testing cars in frontline as well. So the question will be how patients will do after they fail a car in frontline in terms of where you go next. You try a dual car or something like that.

[B]

Thank you. It is promising to be very confusing. Now, Dr. Kamdar, in New review, you both beautifully addressed the challenges of clinical trial design in the relapse refractory space and their interpretation. Could you pick maybe one of them? And then I'll ask Dr. Bartlett to pick another one. And briefly describe what you see as a challenge and how we should think about it in terms of designing clinical trials today.

[C]

I think we addressed several challenges, but I think to me that comes to the fore is access, access to these new immunotherapies. Because these were clinical trials that got panned out. We have now data that they can all be done outpatient. But at the same time, a lot of clinicians are practicing in non clinical trial sites in North America. And I think to get these studies to them is going to be of paramount importance to serve the population they do. I don't think clinical trials rightfully address the fact that there is still a lot of disparity when it comes to sex and age and race and the underserved population of North America that needs to be on these clinical trials. There is also a lot of effort going outside of North America biologically. Could these cohorts of patients have a different setting when it comes to relapsed refractory diffuse large BC cell lymphoma? We do know that a lot of data coming from China is enriched for ABC diffuse large B cell lymphoma. How does it then get percolated into the entire global landscape is a question that I think we'll only address once we appropriately give access to every single patient to get to that clinical trial.

[B]

It's a great point, let's say when you talk about access. So there's the issue of bringing clinical trials to broad populations and to populations that historically have not had access to it. But when a lot of the therapies that are being tested now are around CAR T or bispecific or multi specific antibody therapy, which are very hard to deploy in community settings, that's on or off trial. How do you think about that? How are we going to develop therapies that are going to be easily administered in the kind of settings you describe?

[C]

Even post approval with CAR T cell therapy, I do exercise a little bit of caution because you have to be an atc, although some states of North America, they don't need any of that anymore. That CAR ts can be done in an outpatient setting in a community provider's office. I'm not sure I'm ready for that yet. But with bispecifics, I think they are designed to be that way. Like say for example the Lotus 7 data with Longka plus it looks stellar. As long as we have emergency rooms with the appropriate levels of tosi, we have the resources in a community center trained for doing that. We need to empower our advanced practice providers, especially in settings where there are locum physicians continuously. You know, there's a huge turnover. We also have a huge onus to continue to foster these partnerships where we should be available all the time to make sure that we appropriately get those patients on onboarded. And when that community provider is ready to take that patient back, we should be able to let them go. I think these are just some of the things that can be done to be able to improve access to our patients.

[B]

Thank you. Dr. Bartlett, would you like to describe another challenge?

[D]

Well, first of all, I just want to say one more thing about that challenge, which is I worry a little bit about the bispecifics in the community setting from the standpoint that I think we can easily address the sort of low grade CRS that they sometimes get early on. But I worry about the way these trials are designed with kind of very long treatment and that the sort of opportunistic infections and other infections that come after you've been on this for a few months. And I will tell you a very quick story about a 80 something year old guy that I had on Glofit Gemox for refractory large cell and perking along, doing great, very good response. And it's supposed to be 12 cycles of GloFID and eight cycles of Gemox. And he was having this persistent nausea that I was like, he's not nauseated from the treatment. And it turns out that he has CMV gastritis. And I'm not sure how long it would take someone took me long enough to diagnose those kind of oddball things that happen. And so that is actually another issue I have with sort of trial design is just the not being able to really hone in on how long these treatments need to go on because there's different motivations from the pharmaceutical companies sometimes in terms of more is better. And does everyone need 12 cycles of GloFit in the regimens that that has. We've talked before about some of the EPCOR ones go even longer than that, go indefinite. And then I think you're really running into trouble. And I think we have enough trouble following those patients at an academic site versus a community site where it's some little oddball infection or trying to work up. So I do think that'll be a bit of an issue. I mean, that is one of my issues kind of with the design of these trials is that we can't ever perfect it once it's approved because there's different motivations on the physician and the patient versus the pharma company potentially. And that's where we need our government to help us and approve those kind of dose escalation trials and de escalation trials, which will never come from pharma, which I totally understand. And we have seen trouble with that. Like the trials go on too long. And then you have kind of talked about that in terms of accessibility. But I think even beyond that, we still have a trouble with being too selective in terms of the enrollment. It's very disappointing that everyone with generally any history of CNS lymphoma or even active CNS lymphoma, secondary primary are excluded from so many of these trials. And therefore we've made like so little progress in that area. And it is an area that needs so much work. And I just can't believe that we can't figure out a way. I know again, they don't want anything to happen that would, you know, set the drug adrift. And I totally agree with that. On the other hand, it's hard to do a study only in that subset of patients. So including them and making the eligibility as incorporated as possible right from the beginning and then you can decide, you know, are you going to look at this subset differently when you're done, but would just move things along much more quickly. And also it would make the real world data look like the trial data because we've talked about that before. It's always hard to know how this is going to translate when people don't have someone checking 50 eligibility criteria before the patient goes on the study.

[B]

That's an excellent point. I think one model for that might have been the Transcend trial, where there's a course that fits regulatory and but then they include the patients with allos, cns, lymphoma, et cetera, who don't have to be part of the core analysis, but we learn a lot from them. So there are those trial models that try to straddle both imperatives.

[D]

The other thing that I think would help with access, if we can figure out, I think the. We haven't really talked about the allo cars, but at least in the, you know, my very limited experience with them is in the Alpha 3 trial, which is the MRD positive patients at the end of first line therapy, which again, I think is a place we should be moving with all of this in terms of deciding responses and stuff, that those are all done outpatient in the first, like, I think 24 patients on the study, there's been no CRS and no ICANS. And having a toxicity profile like that would allow you to look at it in earlier lines of therapy, because I think we're always worried about doing something toxic to a group of patients who have a potential cure with an existing treatment. I'm very excited about that and hopefully that would also be something you could do in the community. You get these things off the shelf and they have potentially no or very little CRS or icans. They. That seems much more amenable to being used in any setting almost. I think we're a long ways away from that. I think if the Alpha 3 study pans out, we'll make some progress in that regard.

[B]

Excellent. Dr. Kamdar, any last words on this topic?

[C]

I think the relapsed refractory landscape is really shaping very fast as all of these therapies are getting approved. I think it's really important for us to make sure that we design biologically rational studies, but also make sure that access is improved so that all patients can actually hope to enjoy the benefits of these amazing constructs.

[B]

Thank you for such an important reminder. And thank you both so much for writing such an eloquent review, which I hope our listeners will all go and read if they have not done so. And with that, I thank you for joining this podcast.

[C]

Thank you very much.

[D]

Thank you so much.

[A]

Thank you for listening to this bonus episode of the Blood Podcast. To read these articles, visit bloodjournal. Org. This episode is copyrighted by the American Society of Hematology.