Dr Beitinjaneh Highlights Brexucabtagene Autoleucel for R/R MCL

Amer Beitinjaneh, MD, MPH, MSc, Sylvester Comprehensive Cancer Institute, University of Miami Miller School of Medicine, Florida, highlights a multicenter retrospective study on brexucabtagene autoleucel, which was approved by the FDA in July 2020 and demonstrates encouraging safety and efficacy, for relapsed or refractory (R/R ) mantle cell lymphoma (MCL).

Transcript

Hello, everyone. My name is Amer Beitinjaneh. I am an associate professor of medicine at the University of Miami, Sylvester Comprehensive Cancer Center. I'm a clinical investigator with special focus on stem cell transplant and cellular therapy for lymphoid malignancies.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Beitinjaneh: MCL, which our studies cover, is an aggressive type of B-cell non‑Hodgkin lymphoma (NHL). Those patient has R/R MCL to second line of therapy, have a median overall survival (OS) of less than 1 year.

That prompted in 2016 a national multicenter phase 2 trial called ZUMA‑2, where we looked at a novel chimeric antigen T-cell therapy with CD28 signaling domain called brexu‑cel, was against CD19 R/R MCL. Was a big study published in 2020 in New England Journal of Medicine and led to the approval for brexu‑cel for those subgroups of patients who need mostly that therapy.

Since then, the treatment become commercially available. Some centers, not every center can provide that therapy, start using that on commercial basis. Usually, the clinical studies, when you design, you have more stringent eligibility criteria.

The outcomes of those studies may or may not apply to the general populations in a clinical practice. That's what prompt us to work with other centers—we're about 14 academic centers with experience in CAR‑T. We are under 1 group called US Lymphoma Consortium.

We looked at our own experience with patient with MCL who received brexu‑cel on commercial basis, and try to see if their outcomes will be different than what we've seen in studies, which most of us were involved in years ago. That prompt us to do this very interesting study.

OLN: Could you briefly describe the study and its findings? Were any of the outcomes particularly surprising?

Dr Beitinjaneh: By July 2021, we gathered data for 107 patients who had leukapheresis. They collected cells to produce CAR‑T. We have about 93 patients of those (who) actually received CAR‑T. What's interesting in the study, which we presented at ASH, we have follow‑up presentations in coming meetings that the patient as we expect, the patient population were different than the ZUMA‑2 study.

For example, we have 45% of our patient have the aggressive blastoid or pleomorphic variants versus only 31% in the study. We have 46% has TP53 mutations or alterations and that known risk factors versus only 17% on the ZUMA‑2. We have 7% of our population that have CNS involvement. That was an exclusion criteria for ZUMA‑2.

On the study, we tried to avoid CNS involvement because we're concerned about CNS toxicity. Here on our commercial basis, we have patients with CNS involvement. In fact, 73% of those 107 patients did not meet the criteria on ZUMA‑2 for different reason—for worse performance status, cytopenia, organ dysfunctions, liver or renal dysfunction, and as I mentioned, CNS involvement.

Many patients, they would not be a candidate for the ZUMA‑2 and they still receive the commercial results. We have a short follow‑up. Thus, median for every follow‑up, we have about 3 months on our study.

We see the response rates at 3 months was as good as what we've seen on the ZUMA‑2. We have overall response rate (ORR) of 86%, with complete remission (CR) was 64%, which is remarkable.

We've seen patients who did not receive a BTK inhibitor. On the ZUMA‑2, that was a requirement. You have to fail BTK inhibitor. Here, we have patients, 18%, they did not receive BTK inhibitor. They have actually a better response to patients who failed BTK inhibitors.

Again, the response rate were encouraging that we can, even on different population, still see an excellent response rate. Median OS was 82% with that short follow‑up, and toxicity, which has seen comparable toxicity to ZUMA‑2. We have only 8% have a grade 3 cytokine release syndrome, or more of a grade 3.

For neurotoxicity, or we call it immune effector cell associated toxicity, grade 3 or more were only 33%, similar to what we've seen on ZUMA‑2.

We did not see any associated deaths from those toxicity. We've seen only 26% of those patient require ICU care, which is likely less than what we've seen on the study.

A lot of it could be explained by what we see here, more use of steroids in our real‑world experience management that was driven mainly with more recently published experience with using steroids early on did not really affect the efficacy of CAR‑T and it did reduce the toxicity associated with this CAR‑T.

We've seen the overall outcomes. Efficacy, the same. Toxicity, equal to what we've seen in the study—a little bit better. Those were very surprising and very encouraging to report last ASH. We have more follow‑up to come.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Beitinjaneh: The real‑world experience, in general, we have it now with MCL. We participated with the same consortiums for other type of NHLs. Really, our experience gave a comfort for other cancer center to offer the cell therapy. Not every center is able or feels comfortable offering this intense therapy.

With experience like this, it gives them more comfort and encourages them to use it more often and become an authorized center for those therapy.

That is the big message we'll provide from our study.

More to come where we're trying to get, obviously, more patients. We already enrolled more patients.

We gather more clinical data to see who are those patients who benefit the most and who are the patient who have more complications. We did gather more information already and we gather even more to better understand who those cells fit the best.

We have, for example, an upcoming TCT transplant meeting in April. We have data about MRG. After the treatments, that could affect the outcomes. We'll show that in the coming meeting. We have more to come.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what will be your next steps?

Dr Beitinjaneh: We already included more patients. More and more patients would be able to answer more questions. We're looking for more clinical data point like MRD, looking for more clinical special labs, the effect of the tumor burden, pretreatment, (and) the long‑term outcomes. We're looking forward to see the outcomes of people who progress or did not respond to CAR‑T, what were their outcomes? We already have studies ongoing we plan to be presented and published soon.

OLN: Is there anything else pertaining to your research and findings that you would like to add?

Dr Beitinjaneh: The cellular therapy field is moving very fast. We're very encouraged by that. Our group here is very interested to learn more about how we improve the response rate for those patient who received CAR‑T with different consolidation therapy right after the CAR‑T.

We're very interested in looking at reason why some patient has more resistant tumors than others. We have ongoing correlative studies done in our centers with collaboration with other centers to better understand how we optimize this treatment.