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Videos

Philip L. McCarthy, MD, Director, Blood & Marrow Transplant Program, Department of Medicine, Roswell Park Cancer Institute, comments on the move from doublet therapy to triplet therapy for multiple myeloma.

Triplet Therapy for Multiple Myeloma

In an interview with Targeted Oncology, Hitomi Hosoya, MD, discussed the potential use of ctDNA in the myeloma space, including its ability to sequence BCMA-targeted therapies and reduce the need for bone marrow exams. 

Leveraging ctDNA to Predict Response in Patients With Myeloma Receiving CAR T Cells 

CYAD-01, an autologous CAR T-cell therapy, was tolerable and showed activity in patients with acute myeloid leukemia, myelodysplastic syndromes, and multiple myeloma. 



CAR T-Cell Therapy With CYAD-01 Shows Efficacy in Myeloid Malignancies 

An analysis with longer follow-up of the ZUMA-3 study showed patients with relapsed/refractory B-cell acute lymphoblastic leukemia treated with brexu-cel had a median overall survival of 26 months and a complete response plus CR with incomplete count recovery rate of 71%.

Brexu-cel Generates Durable Responses and Survival Benefits in R/R B-ALL

In a single-institution phase 1 trial, patients with large B-cell lymphoma had high overall response rates with CD22-directed CAR T-cell therapy.

CD22-Directed CAR T-cell Therapy Overcomes CD19 Relapse in LBCL With High CR Rates

The phase 1 POLARIS trial showed a 100% overall response rate for OriCAR-017, a novel CAR T-cell therapy with a new target in relapsed/refractory multiple myeloma. 

GPRC5D-Targeted CAR T-Cells Show Efficacy in Phase 1 R/R MM Trial

Nitin Jain, MD, associate professor in the department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center, discusses future improvements he anticipates for autologous and allogeneic chimeric antigen receptor (CAR) T-cell therapies for B-cell acute lymphoblastic leukemia (B-ALL) and other hematologic malignancies.

 into ‘off-the-shelf’ allogeneic CAR T-cell therapies that avoid the need for leukapheresis which delays the treatment of patients. Although they have shown efficacy, their overall response rates are not equal to that of autologous CAR T cells, to which the vast majority of patients have a response. Jain says that more research is needed to improve response rates so that allogeneic therapies can be a viable alternative, used more rapidly, and made more widely available.

Additionally, he says CAR T-cell therapies need more data supporting their use in earlier lines of therapy. Patients are likely to have better outcomes if they receive CAR T-cell therapy before multiple lines of chemotherapy, like those in the clinical trials that led to FDA approval. Some trials are being designed to establish the efficacy and safety of earlier CAR T-cell therapy, but Jain says he sees it as valuable in early lines, particularly in patients with lower tumor burden who have detectable minimal residual disease.

 In terms of next steps, I think we have to figure out more for the allogeneic CAR T-cell space. We must figure out the clinical activity of these CAR [T-cell therapies] to make sure that they are on par with what we are seeing with our autologous CAR [T-cell therapies]. That's the first step because so far, we are not seeing as high response rates as we have seen with the autologous CAR T-cell setting.

The second step for ALL as a field is to introduce these CAR [T-cell therapies] in the early months of therapy. We don't want patients to have 4 to 5 chemotherapy regimens before they're coming to CAR T cells. We probably should be doing CAR T cells in earlier lines of therapy. Some trials are being designed right now, but the approval is for relapsed/refractory ALL, so we should not wait. I think for multiple lines of therapy, earlier lines of therapy, and in lower tumor burden minimal residual disease–positive patients, that is where the field of CAR T-cell therapy is moving.

Nitin Jain, MD, discusses future improvements he anticipates for autologous and allogeneic chimeric antigen receptor T-cell therapies for B-cell acute lymphoblastic leukemia and other hematologic malignancies.

The Future of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia

Lori Leslie, MD, assistant professor, Hackensack Meridian School of Medicine, director, Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs, John Theurer Cancer Center, discusses ongoing clinical trials that are exploring chimeric antigen receptor (CAR) T-cell therapy for the treatment of B-cell malignancies.

There are a lot of other studies looking at CD19 CAR T cells across different B-cell malignancies. We've got ZUMA-2 which looked at indolent lymphomas and led to an approval in follicular lymphoma based on overall response rate of 94% and a complete response rate close to 80% in patients with relapsed/refractory disease. I think further follow up from ZUMA-5 [NCT03105336] will let us know if this is a potentially curative option for our patients with the more indolent lymphomas, they can have relapses 10, 20, even 30 years down the line.

 We have CD19 CAR T approved in DLBCL and that is being investigated in earlier lines of therapy. Recently published in a New England Journal of Medicine is the ZUMA-7 [NCT03391466] study that looked at CD19 CAR T-cell therapy axicabtagene ciloleucel [axi-cel; Yescarta] as second line therapy compared to standard of care, high dose therapy and autologous stem cell transplantation. This was the first initiated and first to meet its primary efficacy analysis among many different studies in this space trying to transform second line DLBCL therapy, away from high dose chemo and consideration of autologous stem cell transplant, particularly for patients with chemo-sensitive disease and instead sparing patients the toxicity of high dose chemo and transplant and allowing them to go straight to CD19 CAR T-cell therapy in the second line setting.

 We are taking the CD19 CAR T cells and adjusting the types of lymphoma where we can use them and the lines of therapy where we can use them. Moving forward, what's probably transforming this space the most are potentially CAR T-cell products that target different antigens on the tumor cell, but also dual targeting CAR T, so these targets CD19 and there are other CAR T products that target more than 1 tumor antigen. Instead of autologous products, there are allogeneic off the shelf or their cell therapy products that may be T cells, they may be NK cells. There are some other ways of conjugating an antibody to an effector T-cell to have a CAR T-like effect with a more simple and potentially less expensive manufacturing process. There are a lot of ways that this space is moving forward quite rapidly in a way that's incredibly hopeful and promising for our patients.

Lori Leslie, MD, discusses ongoing clinical trials that are exploring chimeric antigen receptor T-cell therapy for the treatment of B-cell malignancies.

Studies of CAR T Cells for B-Cell Malignancies

Nitin Jain, MD, associate professor in the department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center, discusses the progress of allogeneic chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoblastic leukemia (B-ALL) and other hematologic malignancies.

CAR T-cell therapy has advanced in recent years with several products being approved for use, but these are primarily autologous CAR T-cell therapies. They are derived from the patient’s T cells after being removed through leukapheresis and then turned into CAR T cells before being infused into the patient again.

According to Jain, there are many clinical trials of allogeneic CAR T-cell therapy in which CAR T cells can come from a healthy donor, umbilical cord blood, or in vitro cell lines. These therapies can be given more quickly since they don’t require leukapheresis, can be given off the shelf, and do not require bridging therapy. Though some of these therapies have shown efficacy in trials, there are limited data at this time compared with the clinical experience with autologous CAR T-cell therapies.

 The field of CAR T-cell [therapy] has moved rapidly in the last few years. Most of the approved CAR T products right now are autologous CAR T cells, which are T cells derived from the patients after leukapheresis, which drive these T cells and make them into CARs. The field of allogeneic CAR T cells is evolving, where you derive the T cells not from the patient, but from either a healthy donor, or from umbilical cord blood, or from some type of cell line. These are a new wave of CAR T cells which are in clinical trials right now.

The advantages are these CAR T cells are available right away. You don't have to wait for leukapheresis, you don't have to wait for bridging chemotherapy, and they're available off the shelf. These can be given to patients almost right away. That is the biggest advantage of these CAR T cells. Obviously, very limited data is available at this time in terms of clinical data for these CAR T cells compared with what we know about autologous CAR T cells.

Nitin Jain, MD, discusses the progress of allogeneic chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia and other hematologic malignancies.

Advantages of Allogeneic CAR T-Cell Therapy for Hematologic Malignancies

Mazyar Shadman, MD, MPH, attending physician, Hematologic Malignancies
Fred Hutchinson Cancer Center, and associate professor, Medical Oncology Division University of Washington School of Medicine, explains how community oncologists can care for their patient after they have been treated with chimeric antigen receptor (CAR) T cells.

Normally, CAR T-cell therapy is administered at academic centers, and follow-up treatment occur at the same institutions, according to Shadman. But most patients eventually return to the care of an oncologist in their community. Shadman explains that there are certain adverse reactions to CAR T-cell therapy that oncologists can identify and treat.

Our community oncology colleagues most of the time don't take care of patients immediately after CAR. But I think it's very important for them to be familiar with the type of side effects that patients may develop after CAR T therapy, both because of risk and benefit assessment before referring a patient for CAR T therapy, to make sure patients have a good understanding of the the adverse events and the toxicity that's associated with with it. And sometimes when we send patients back to the primary oncologist, some of the toxicities are ongoing. So, I think it's very important for them to be familiar with the rate and for the type of side effects that patients may develop after CAR T therapy.

Mazyar Shadman, MD, MPH, explains how community oncologists can care for their patient after they have been treated with chimeric antigen receptor T cells. 

Identifying Post CAR-T Issues in Community Oncology Patients

Nitin Jain, MD, associate professor in the department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center, discusses clinical trials investigating allogeneic chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoblastic leukemia (B-ALL) and other hematologic malignancies.

As opposed to autologous CAR T-cell therapies, allogeneic CAR T cells do not need to be derived from leukapheresis of the patient and can be made available more quickly. Jain highlights the CALM trial (NCT02746952) of UCART19, an anti-CD19 allogeneic CAR T-cell therapy, in which there was a 67% complete response rate among 21 patients with B-ALL. In this trial, the treatment served as a bridging therapy to hematopoietic cell transplant since the cells did not persist long term.

Another allogeneic CAR T product, PBCAR0191, was investigated in a trial (NCT03666000) of patients with ALL and non-Hodgkin lymphoma. Its results were presented at the 2021 American Society of Hematology (ASH) annual meeting and showed clinical activity in patients including some who had received prior autologous CAR T-cell therapy.

Other ongoing clinical trials noted by Jain include the phase 1/2 BALLI-01 (NCT04150497) trial of UCART22 for B-ALL, the phase 1 trial (NCT03190278) of UCART123 for acute myeloid leukemia, and a phase 1 trial (NCT04629729) of FT819 for B-cell malignancies. He says more data may be presented in the next year from various trials.

 One of the trials is [for] a product called UCART19, which I believe was the first trial in the United States with allogeneic CAR T cells for B-ALL. That was published last year in the journal 

 where 21 patients were treated with B-ALL. We saw that there were relatively high rates of responses in about 60% to 70% of the patients. And more so, I would say, it was a bridge to transplant because these CAR T cells do not last forever. Therefore, most of these patients then consulted with a transplant.

Another trial is by a company called Precision Biosciences. We had an oral presentation at ASH last year, where again these allogeneic CAR [T cells] derived from healthy human donors were able to show clinical activity, both for ALL as well as for non-Hodgkin lymphoma. I should say there are several other clinical trials in development, including for UCART22, UCART123 for AML, Fate Therapeutics [FT819]. There are many other companies which are developing off-the-shelf allogeneic CARs, and hopefully we'll see some data maybe at this upcoming ASH or in next year’s meetings as well.

Nitin Jain, MD, discusses clinical trials investigating allogeneic chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia and other hematologic malignancies.

Overview of Allogeneic CAR T-Cell Therapy Trials for ALL, AML, and NHL

Adam Cohen, MD, director of myeloma immunotherapy at Penn Medicine and associate professor of medicine at the Hospital of the University of Pennsylvania, discusses when patients should receive chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory multiple myeloma (R/R MM).

Two B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies have been approved for R/R MM: ciltacabtaene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma). Patients must have received 4 prior lines of therapy including a proteasome inhibitor, immunomodulatory drug (IMiD), and anti-CD38 antibody. Cohen says that older patients can be treated as long as they have good performance status, but severe cardiac and pulmonary conditions may cause patients to not be candidates for CAR T-cell therapy. However, those with renal failure may be treated successfully by modifying the level of lymphodepleting chemotherapy received.

Cohen recommends that patients be referred for CAR T-cell therapy when they progress on third-line therapy and move on to fourth-line therapy, since there may be long wait times to receive these therapies. They can then receive CAR T cells if they fail to have a strong response to fourth-line therapy. Referring patients early is crucial due to the time it takes to manufacture CAR T cells, since patients who progress rapidly may not live long enough to benefit from CAR T-cell therapy even with bridging therapy.

 Right now, both BCMA CAR [T-cell] products in myeloma are approved for patients who have had at least 4 prior lines of therapy, which must include a proteasome inhibitor, IMiD, and a CD38 antibody. There's no real upper age limit for CAR T-cell therapy. We've treated patients in their early 80s, but they do need to be fairly robust to be able to withstand cytokine release syndrome. Typically, we would exclude patients with advanced heart failure or uncontrolled cardiac conditions, oxygen independence, COPD [chronic obstructive pulmonary disease], or other severe pulmonary conditions or very poor performance status. We don't think renal failure necessarily is an exclusion. They were excluded from the trials, but we have been able to treat patients with commercial products even with profound renal dysfunction, just modifying the lymphodepleting chemotherapy.

I think the time to think about sending your patient into the CAR T-cell center should be when they're progressing on their third-line therapy and you're thinking about starting a fourth-line treatment. Then it would be helpful if you're thinking there would be a CAR T-cell candidate to get them into the center so we can assess them at the same time and add them to the waitlist for CAR T cells. Unfortunately, there's still limited manufacturing slots for these, so there can be a several month waitlist. That way, that patient is already in the system and if they don't respond to fourth-line treatment, or even if they are responding well but it's not a deep response, we may be able to take them to CAR T cells while they're under good disease control.

We're learning that patients who are really progressing rapidly while we're trying to collect T cells and then manage them with bridging therapy during the manufacturing [process] has been challenging. Some of those patients unfortunately never make it to their CAR T cells because their disease just takes off. I think it's better to send them in while they're still under some control and while we have good bridging options.

Adam Cohen, MD, discusses when patients should receive chimeric antigen receptor T-cell therapies for relapsed/refractory multiple myeloma. 

Identifying Patients With R/R MM Who Should Receive CAR T-Cell Therapy

Peter A. McSweeney, MD, hematologist/oncologist at the Colorado Blood Cancer Institute, discusses the challenges that come with administering chimeric antigen receptor (CAR) T-cell therapy. He also explains how CAR T cells entering the second-line may change the ways community practices choose treatments for their patients.

The key challenge that small community practices face when administering patients CAR T-cell therapy is the lack of infrastructure. While larger practices have similar resources to those in academic centers, smaller practices often require a referral to an academic center in order to give a patient CAR T-cell therapy.

According to McSweeney, with CAR T cells now entering the second-line setting for various cancer types, community practices need to keep in mind how they can incorporate this into the treatment strategy for patients at first relapse. For physicians not administering this CAR T-cell therapy, it is important to get patients referred quickly and to the correct site.

The biggest challenge for administering these CAR T cells in the community is developing a program that has the appropriate expertise and infrastructure for this type of work. It's a very multifaceted type of therapy, it draws on inpatient and outpatient arrangements that meet the needs of the patients, and there is a need for subspecialty support in the hospital for patients who have complications with the therapy.

What I think is very important for second-line therapy is that the community practice is aware of these changes because patients are now moving into this as the therapy at first relapse, or at least incorporate this into the treatment strategy at first relapse, so one needs to know this. In some instances, the timing of therapy and the urgency of referral is a big issue. The physicians in the community who are not administering this therapy need to be aware and get the patient referred quickly to the appropriate places, particularly for diseases like diffuse large B-cell lymphoma in initial relapse or that is resistant to primary therapy.

Peter A. McSweeney, MD, discusses the challenges that come with administering chimeric antigen receptor T-cell therapy. He also explains how CAR T cells entering the second-line may change the ways community practices choose treatments for their patients.

News

Administering CAR T-Cell Therapy in the Community Setting

Steven M. Albelda, MD, Wiliam M. Measey professor of Medicine at the University of Pennsylvania Perelman School of Medicine, discusses what he expects the future of chimeric antigen receptor (CAR) T-cell use in solid tumors to look like.

According to Albelda, there has been a lot of success with the use of CAR T cells in blood tumors, but the same has not been reflected in the solid tumor space.

With a number of ongoing trials examining CAR T cells in various types of cancers, including phase 1 studies in brain, renal/hepatic, colorectal, ovarian, pancreatic, prostate, thoracic, and head and neck cancers, experts hope the future will bring impressive results from the use of CAR T cells in solid tumors.

With the success in blood tumors, the field is really excited about trying to achieve the same success in solid tumors, but it may take a while. If you think about how long it's taken for monoclonal antibody therapy to become a mainstay or more traditional gene therapy, an area I started in, it could sometimes take 20-25 years of iterative progress, or sometimes a big breakthrough comes that changes everything. I think the field is really hoping towards that. We are making incremental changes, and hopefully in the next 5 years, we will be close to the stage that we're at with the blood tumors.

Steven M. Albelda, MD, discusses what he expects the future of chimeric antigen receptor T-cell use in solid tumors to look like.


CAR T-Cell Use Generates Hope in Solid Tumors

Nicolas Gazeau, MS, postdoctoral research scholar at Fred Hutchinson Cancer Center, discusses next steps and unmet needs following a positive retrospective study of anakinra (Kineret) for the management of neurotoxicity and cytokine release syndrome (CRS) in patients who received chimeric antigen receptor (CAR) T-cell therapy.

Investigators are looking at drugs for managing immune effector cell–associated neurotoxicity syndrome (ICANS) and CRS, which are potentially dangerous adverse events (AEs) associated with CAR T-cell therapy. This retrospective study of 43 patients who received CAR T-cell therapy showed faster recovery from CRS and ICANS and lower non-relapse mortality for those who received a higher dose—8 mg/kg per day—of anakinra. Antitumor response to the CAR T-cell therapy was also improved in this group.

Gazeau says there is a need for a randomized prospective study of anakinra to confirm these results so it can be approved by the FDA to manage CRS/ICANS, and a study [NCT04359784] is in progress at his institution. In general, more research is needed on the causes of CRS and ICANS to determine how CAR T-cells can maintain their efficacy without having serious AEs.

Besides corticosteroids, tocilizumab (Actemra) has been shown to be effective for CRS but not ICANS, and more options are needed.

 If we have a patient with refractory ICANS of CRS with a lot of steroids, we can think about anakinra as a treatment. If we use anakinra in the clinic, it is probably more relevant to use it with a high dose. We have to wait for sure to get the FDA approval for the treatment [with a] prospective study. Those prospective studies are ongoing.

We need prospective studies with a control group to prove if our patients have the benefits of this treatment. We have to think more about the CAR T-cell construct to keep the good efficacy of CAR T cell and try to avoid the AEs. We have to find another way to manage these toxicities. There are steroids. There is tocilizumab and now, maybe anakinra. There are also molecules that can could be interesting. We have to proceed with that for sure.

Nicolas Gazeau, MS, discusses next steps and unmet needs following a positive retrospective study of anakinra for the management of neurotoxicity and cytokine release syndrome in patients who received chimeric antigen receptor T-cell therapy.

Unmet Needs for Managing CRS and ICANS Due to CAR T-Cell Therapy

Peter A. McSweeney, MD, hematologist/oncologist at the Colorado Blood cancer Institute, discusses challenges with implementing chimeric antigen receptor (CAR) T-cell therapy in some community oncology practices.

There are large and small community oncology practices, explains McSweeney. Larger centers often have the resource to administer CAR T-cell therapy the way it is done in academic centers. For small community practices, giving CAR T-cell therapy usually requires a referral to an academic center.

The key challenge in the way of small community practices is the lack of infrastructure, according to McSweeney.

 Community practices come in different types. There are some quite large community malignancy programs, which are actually really clinically the equivalent of academic centers. And so, they handle all this pretty much according the same algorithms as the academic centers. The issue of you know, smaller oncology practices in this area really is, you know, not an issue right now. There's been very little penetration of CAR T-cell therapy, and these types of cellular therapies to those practices, although they are subtly showing interest in trying to develop capability.

 The biggest challenges for administering these CAR T cells in the community are developing a program that has the appropriate expertise and infrastructure for this type of work. And it's a very multifaceted type of therapy draws on inpatient and outpatient arrangements that meet the needs of the patients. And also the is a need for subspecialty support in the hospital for patients who have complications with the therapy.

Peter A. McSweeney, MD, discusses challenges with implementing chimeric antigen receptorT-cell therapy in some community oncology practices. 

Challenges With CAR T Therapy in Community Practices

In the coming years, we are going to continue to see the development and FDA approval of a lot of novel targeted drugs for patients with relapsed large-cell lymphoma. And I think specifically, a lot of these drugs are being developed for patients who are failing a transplant, or are ineligible for a transplant, or cannot get into a remission with salvage chemotherapy. I mentioned tafasitamab. I talked a little about CAR [chimeric antigen receptor] T cells, polatuzumab. There are several other drugs also being developed in this space, which are biological, and some of them are targeted drugs.

As we move forward, as these drugs all become available to the clinician, the big thing is going to be deciding which of these drugs to use in which patient populations. This decision should be based on the drug&rsquo;s adverse-effect profile, as well as the activity of the drug. In patients, for example, who potentially have compromised organ function, we might not want to use drugs like CAR T cells that could have a really tough effect on their performance status, or drugs that maybe affect heart function or kidney function.

In patients who are of great performance status and are great candidates, I would probably pick CAR T-cell therapy. In patients who are older and have compromised organ function, I might be thinking about a more biological regimen, like tafasitamab plus lenalidomide or, potentially, an emerging novel biological regimen. It&rsquo;s important to look at the entire profile of the drug, or of the combination, when you&rsquo;re making these decisions. Again, not only adverse effects but also what the goals of therapy are and what the activity of the combination or the single drug is that you&rsquo;re planning on using.

DLBCL

Bladder Cancer

Tailoring Therapy for Patients With DLBCL

Thank goodness there are a lot of other things in this space. There are a lot of drugs that are being developed for patients who either relapse after a transplant, or are ineligible for a transplant, or cannot get into remission prior to transplant. There recently was the FDA approval of the combination of the drugs bendamustine-rituximab plus polatuzumab. This is an anti-CD79b antibody, and this is also approved in patients with relapsed large-cell lymphoma.

There are ongoing trials with many other targeted drugsdrugs that are targeting different cell surface antigens. We have several combination trials ongoing looking at the potential benefit of drugs like venetoclax and other next-generation immunomodulatory drugs. Hopefully, as these trials continue to progress, we&rsquo;ll see other good options for patients with relapsed large-cell lymphoma.

I think 1 of the most exciting things to come out in the last couple [of] decades for large-cell lymphoma is CAR [chimeric antigen receptor] T-cell therapy. The reason CAR T cells are so exciting is because they use a very novel mechanism to target the relapsed large-cell lymphoma. This is a mechanism, or I should say an approach that has been very successful in children with relapsed B-cell leukemia, and is also being used in many other different types of B-cell malignancies. Essentially, what we do is take the patient&rsquo;s own T cells and train them in the lab to recognize cancer cells. These T cells are then reinfused into a patient, where they expand and then go on the attack. What happens is these T cells then find, recognize, and kill malignant B cells within the patient.

These approaches, again using CAR T cells in relapsed large-cell lymphoma, have been associated with long-term or durable remissions in anywhere from 30% to 50% of patients. Many of these patients had failed a prior autologous stem cell transplant or were ineligible for a stem cell transplant. Again, the most exciting thing is not just how they work but that these drugs are working very well, potentially curing patient populations for which we did not have a lot of options previously.

These drugs are associated with adverse effects, so they are not without risk. Many times, patients can develop very severe cytokine release syndrome. This is a syndrome that can lead to multiorgan damage. It can sometimes lead to very severe neurological changes in the patientseverything from seizures, to patients having respiratory failure, to confusion. Unfortunately, at least today, we do not have a good way to predict for whom or when adverse effects will occur.

Many of these patients are watched very closely for the first 2 weeks after receiving CAR T cells. It&rsquo;s quite uncommon to have late adverse effects with CAR T cells, with the exception of cytopenias. If patients make it the first 2 weeks and have a remission, especially a complete remission, it&rsquo;s likely that they can maintain a durable remission or a cure. So these are very exciting times.

There are several next-generation CAR T cells being developed, and hopefully some of these next-generation drugs will result in a veryor I should say

favorable adverse-effect profile with, potentially, even higher complete response rates.

CAR T-CELL THERAPY

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