Michael Wang, MD

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 This is a perfect segue to CAR [chimeric antigen receptor] T-cell therapy. Caron, you were part of a real-world consortium data set looking at CAR T. Now, when CAR T was first studied on the ZUMA-2 clinical trial, it was for BTKi [Bruton tyrosine kinase inhibitor] intolerance or resistance. Where are we now?

 Well, I think the first place we are is that the FDA actually approved a much broader label, so it’s any relapsed or refractory mantle cell lymphoma. I think it was a very forward-thinking approval because of all of the studies that are now incorporating BTK inhibitors in the frontline setting, you don’t want patients to have to have gone through 2 lines of therapy if all of the effective therapies are being given in the front line. Thus, I think that was very forward thinking.

It is available now for patients with any relapsed/refractory mantle cell lymphoma. The vast majority of patients in the real world, as we’ve seen from 2 different series, one from Europe and one from the United States, have seen a BTKi. But what’s very interesting is there were about 18% of patients in the US series, which was about 96 patients I think in total, who had not seen a prior BTKi, and their results following brexucabtagene autoleucel were identical to patients who had seen a BTKi. I think this is the big question, is prior exposure to a BTKi important for T-cell fitness and the T-cell product, and at least from this very small cohort, it suggests that maybe it is not as important as we might have thought.

I think the data from ZUMA-2 have been replicated in these real-world series. Just like we’ve seen in large cell lymphoma, it’s very consistent. The response rates are consistent, the CR [complete response] rates of nearly 70% are consistent, and so far, what we’re seeing in terms of the 1-year progression-free and overall survival are very consistent, and the toxicities are consistent. I think 70% of patients would not have been eligible for the pivotal clinical trials. So we can now apply these therapies to a broader population of patients: patients with renal failure, heart failure, lower blood cell counts and bone marrow dysfunction, and still see the same excellent results. They continue to be really transformative, I think, for our patients.

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Experts discussed the ZUMA-2 clinical trial of brexucabtagene autoleucel.

Brexucabtagene Autoleucel in R/R Mantle Cell Lymphoma

spoke with Michael Wang, MD, professor, Department of Lymphoma & Myeloma, University of Texas MD Anderson Cancer Center, to learn more about the FDA approval of lisocabtagene maraleucel (liso-cel, Breyanzi).

The liso-cel clinical trial assessed both large B- cell lymphoma and mantle cell lymphoma (MCL). The agent was found to be both effective and tolerable in these indications. In patients with relapsed MCL, the overall response rate was 84% and the complete response (CR) rate was 67%. Wang discussed liso-cel in comparison with brexucabtagene autoleucel (Tecartus).

 The liso-cel clinical trial were in large-cell lymphoma and mantle cell lymphoma. The large B-cell lymphoma trial has been reported to be very efficacious, and the deciding factor for toxicity is tolerable. During the last ASH meeting, M. Lia Palomba, MD, from Memorial Sloan Kettering Cancer Center, myself, and other colleagues reported the efficacy of liso-cel in relapsed mantle cell lymphoma from 32 patients.

 The overall response rate was 84% with a complete response rate of over 66%. We cannot compare trials across trial, but the efficacy of the brexucabtagene autoleucel can put us into the right context. The overall response rate of was 93% and the CR rate was 67%. So, you can see the CR rates between the 2 products in the 2 separate trials are relatively close. I really think the data on liso-cel relapse in relapsed/refractory mantle cell lymphoma shows good efficacy, and quite has been well-tolerated in relapsed/refractory mantle cell lymphoma.

The professor from University of Texas MD Anderson Cancer Center discussed the FDA approval of lisocabtagene maraleucel.

Liso-Cel's Efficacy in R/R Large B-Cell Lymphoma: Michael Wang, MD

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spoke withBijal Shah, MD, MS, associate member, Department of Malignant Hematology, Moffitt Cancer Center, and Michael Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, to learn more about the need for collaboration between academic and community practices for patients who receive CAR T-cell therapy.

The hematologists explained how integrating primary care physicians into the post–CAR T-cell therapy management of patients with hematologic malignancies is difficul and engaging community practices has not been a priority in many cases. However, integrating primary care physicians is important because they can closely monitor heart function and recovery of immunoglobulin while supporting the patient.

Gaps in communication still exist, particularly when patients come into the emergency room with CAR T-cell therapy–related complications, such as infections. Moreover, these gaps have been further exacerbated with the onset of the COVID-19 pandemic, Wang says.

Aggressive treatments with vaccines, IVIG, and prophylactic antibodies for patients who develop infections after CAR T-cell therapy are helpful, but managing patients who develop CAR T-cell therapy–related complications away from the center in which they received CAR T-cell therapy is challenging. Furthermore, this underscores the need for close collaborations and partnerships between academic and community practices, Shah concludes.

The hematologists from Moffitt Cancer Center and MD Anderson Cancer Center discussed the need for collaboration between academic and community practices for patients who receive CAR T-cell therapy.

The Need for Academic and Community Collaboration With CAR T-Cell Therapy: Bijal Shah, MD; Michael Wang, MD

spoke with Bijal Shah, MD, MS, associate member, Department of Malignant Hematology, Moffitt Cancer Center, and Michael Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, to learn more about managing high-risk mantle cell lymphoma (MCL).

While chimeric antigen receptor (CAR) T-cell therapy can be useful in this population, , patients with high-risk disease who are not identified early may not be eligible for the therapy,  which requires apheresis and bridging therapy. Identifying patients early is critical to ensure all potential treatment options are available for use. High-risk MCL, which  is characterized by blastoid or 

 variants, can grow very quickly. Moreover, although indolent MCL may be actively monitored, high-risk MCL often requires aggressive treatment. 

Currently, a gap between referring community practices and academic practices exists because community practices may not be as familiar with identifying high-risk disease. As such, sharing knowledge of markers of high-risk disease and the differences between indolent and high-risk MCL is an important step to bridge that gap, Wang concludes.

The hematologist from Moffitt Cancer Center and MD Anderson Cancer Center discussed CAR T-cell therapy and other treatment options for MCL.

Challenges in Managing High-Risk Mantle Cell Lymphoma: Bijal Shah, MD; Michael Wang, MD

spoke with Bijal Shah, MD, MS, associate member, Department of Malignant Hematology, Moffitt Cancer Center, and Michael Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, to learn more about how to navigate the referral process for  chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies.

Shah touched on the difficulties of this process. Patients who receive CAR T-cell therapy are expected to stay in or around the treatment center for 2 to 4 weeks, depending on the severity of CAR T-cell therapy–related toxicities, Wang said.

Ultimately, close collaboration between community and academic practices is needed to ensure the referral process is optimal for patients, Shah and Wang conclude.

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The hematologists from Moffitt Cancer Center and University of Texas MD Anderson Cancer Center discussed navigating the referral process for CAR T-cell therapy in hematologic malignancies.

Navigating CAR T-Cell Therapy Referrals: Bijal Shah, MD; Michael Wang, MD

spoke with Bijal Shah, MD, MS, associate member, Department of Malignant Hematology, Moffitt Cancer Center, and Michael Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, to learn more about managing chimeric antigen receptor (CAR) T-cell therapy–related cytokine release syndrome (CRS) and neurotoxicity in leukemia and lymphoma.

Shah and Wang discussed strategies that may mitigate emerging CRS in patients with leukemia or lymphoma who receive CAR T-cell therapy, including earlier integration with tocilizumab (Actemra) and, in some cases, corticosteroids. However, determining when to intervene with these therapies can be difficult and requires balance.

For example, early intervention with steroids can hinder T-cell expansion, whereas late intervention can leave a patient with more severe CRS that is associated with high fever, hypotension, and hypoxia, Wang explains. Moreover, untreated neurotoxicity can cause seizures and late-onset toxicities.

As such, one strategy for managing CRS includes early intervention with tocilizumab, punctuated doses of corticosteroids, and close monitoring, Shah explains. However, tocilizumab does not treat neurotoxicity and, although effective, utilizing steroids sparingly can exacerbate neurotoxicity. Ultimately, a balance between therapeutic intervention and managing emerging CRS and neurotoxicity is needed, Shah and Wang conclude.

The hematologists from Moffitt Cancer Center and MD Anderson discussed managing CAR T-cell therapy-associated toxicities.

Managing CAR T-Associated Neurotoxicity and CRS: Bijal Shah, MD, MS; Michael Wang, MD

spoke with Bijal Shah, MD, MS, associate member, Department of Malignant Hematology, Moffitt Cancer Center, and Michael Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, to learn more about the main CAR T-cell therapy–associated toxicities in hematologic malignancies.

Shah and Wang discussed cytokine release syndrome (CRS) and neurotoxicity, which are unique toxicities commonly associated with CAR T-cell therapy in patients with hematologic malignancies. They also discussed infections that can arise with this treatment because CAR T-cell therapy is thought to enhance B-cell aplasia. This compromises cellular immunities and makes patients susceptible to potentially life-threatening infections, Wang explained. It is important to monitor patients with hematologic malignancies who receive CAR T-cell therapy for potential cardiac toxicities as well.

Although the toxicities associated with CAR T-cell therapy are broad, they are routinely seen in real-world clinical practice and require specialized management, Shah and Wang conclude.

The hematologists from Moffitt Cancer Center and The University of Texas MD Anderson Cancer Center discussed CAR T-associated toxicities.

CAR T-Cell Therapy Associated Toxicities: Bijal Shah, MD, MS; Michael Wang, MD

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the importance of additional CAR T-cell therapy research in mantle cell lymphoma (MCL). 

CAR T-cell therapy is a new ​therapeutic modality in MCL, so additional research is needed, says Wang.

In the phase 2 ZUMA-2 trial, it was discovered that certain cytokines are associated with efficacy and toxicity​, explains Wang. Moreover, future research efforts should aim to develop new measures that could enhance efficacy and minimize​ toxicity in these patients. 

As the ZUMA-2 trial was relatively small, larger studies are necessary to obtain further insight on​ the utility of minimal residual disease, as well as cytokine ​profiling, Wang concludes. 

Michael Wang, MD, discusses the importance of additional CAR T-cell therapy research in mantle cell lymphoma. 

Dr. Wang on Future Research With CAR T-Cell Therapy in MCL 

Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the safety profile of ​the CAR T-cell therapy brexucabtagene autoleucel (Tecartus; formerly KTE-X19) in ​relapsed/refractory mantle cell lymphoma (MCL). 

FDA approved brexucabtagene autoleucel 

for the treatment of patients with relapsed/refractory MCL. The approval was based on data from the phase 2 ZUMA-2 trial, in which a single infusion of the CAR T-cell product led to an 87% objective response rate and 62% complete response rate.

Regarding safety, the rates of cytokine release syndrome (CRS) and neurotoxicity ​were favorable, says Wang. CRS ​onset typically occur​ed within 1 or 2 days ​after infusion and peak​ed around 1 week, while neurotoxicity peak​ed between day​s 10 and 14.

Both CRS and neurotoxicity were well managed with tocilizumab (Actemra) or corticosteroids, ​Wang explains. ​Though, 1 patient died as a result of CRS.

Michael Wang, MD, discusses the safety profile of ​the CAR T-cell therapy brexucabtagene autoleucel in ​relapsed/refractory mantle cell lymphoma.

Dr. Wang on the Safety Profile of Brexucabtagene Autoleucel in Relapsed/Refractory MCL 

Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discusses the safety and effectiveness of the autologous anti-CD19 CAR T-cell therapy KTE-X19 in patients with higher- versus lower-risk mantle cell lymphoma (MCL).

Results from the primary analysis of the phase 2 ZUMA-2 trial showed that KTE-X19 had comparable pharmacology and clinical outcomes in patients with higher versus lower-risk MCL defined by 

 mutation or Ki-67 PI, says Wang. This is promising, because the goal is to develop a therapy that will not discriminate against high-risk factors, explains Wang.

No statistically significant difference was observed with regard to the complete response rate and the overall response rate between the 2 groups, says Wang. If this were not the case, and differentiation was noticed in the results, this would suggest that the CAR T-cell therapy is no different than treatments of the past, such as chemotherapy and targeted therapy, adds Wang. KTE-X19 may offer the ability to overcome challenges faced with effectively treating patients with higher-risk MCL, concludes Wang

Michael Wang, MD, discusses the safety and effectiveness of the autologous anti-CD19 CAR T-cell therapy KTE-X19 in patients with higher- versus lower-risk mantle cell lymphoma.