Dr Christopher Flowers: Liso-Cel Approval for Mantle Cell Lymphoma Changes the Treatment Strategy

Christopher Flowers, MD, of MD Anderson Cancer Center

Although mantle cell lymphoma is an incurable disease with standard therapy, the addition of lisocabtagene maraleucel to providers’ armamentarium may mean sustained remissions for patients, said Christopher Flowers, MD, division head in the Division of Cancer Medicine at MD Anderson Cancer Center, and chair and professor of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center.

The FDA recently approved lisocabtagene maraleucel (Breyanzi) for the treatment of adults with relapsed and refractory (R/R) mantle cell lymphoma after 2 lines of systemic therapy, including a Bruton tyrosine kinase inhibitor.¹ The approval came just weeks after the chimeric antigen receptor (CAR) T-cell therapy received accelerated approval to treat R/R follicular lymphoma after 2 or more lines of systemic therapy.²

This transcript has been edited for clarity.

The American Journal of Managed Care^® (AJMC^®): One of the big questions in mantle cell lymphoma—because there's less data compared to some of the other subtypes—is, now that we have this option, how do clinicians decide in terms of sequencing, since we also will potentially have bispecific antibodies out there?

Flowers: Mantle cell lymphoma is a disease that is typically not curable with standard approaches to therapy. This is a patient population that really needs a multitude of options for their care, to be able to provide options for sustaining long-term disease control over prolonged periods of time. Having this new approval in mantle cell really creates a new option with cellular therapy for this patient population that we've seen can produce remissions, and then provide sustained remissions for patients. It adds considerably to the armamentarium that clinicians will have to be able to care for patients and to keep them disease free for long periods of time.

AJMC: When lisocabtagene maraleucel was first developed, one of the advantages cited was that the different manufacturing process would produce fewer adverse effects and less toxicity. How has that borne out over time? Is that what you've seen in practice?

Flowers: Well, I think the challenge with comparing CAR T-cell therapies head-to-head is there never has been a head-to-head trial to say, “With the same patient populations, how would patients do with one product vs the other?” But I think in practice, one of the things that we've seen is that the unique and serious adverse events with cellular therapies—like cytokine release syndrome or neurologic toxicities—in patients who have been treated with the lisocabtagene maraleucel product, that those appear to be manageable for the majority of patients, and they're ones that are tolerable, and we can get patients through in the acute period after they receive therapy. Then after that, there's not ongoing treatment required with a cellular therapy like CAR T cells.

AJMC: One of the other features that was cited in the release is that a number of the patients in the TRANSCEND NHL 001 study (NCT02631044) were treated in in an outpatient setting or community setting.³ Could discuss what this means in terms of the accessibility of this therapy?

Flowers: That's really an important component for making this type of therapy accessible for many more patients. I think there are a number of factors. One, is the availability and the centers where this is being provided. The second, is the ability to give it as an outpatient, rather than as an inpatient and requiring hospitalization. I think that component of access makes this also an important new advance to see that patients were treated in community-based practices, where they can receive cellular therapies. Now, those community-based practices need to have a degree of specialization to be able to give cell therapy, but it's important that that can be done in practices as an outpatient. Then a third key component to access is obviously affordability of therapy and making sure that this is something that through insurance-based coverage is affordable to patients so that they can have access to it.

AJMC: One of the other things that was mentioned is capacity. I know with some CAR T-cell therapies there have been concerns about manufacturing capacity. Some centers have more patients eligible than they have slots to give, and the commitment has been made that that's not going to be the case and we're getting better access in terms of the manufacturing capacity. What's been your experience with lisocabtagene maraleucel? Have you been able to get all the therapy that you need for the patients who meet the criteria?

Flowers: With these 2 new approvals, those are things that will all be borne out in clinical practice over time. So, those are things that we will need to see in the future, to make sure that all the patients who need cellular therapies really have access to them, and can benefit from it.

AJMC: In terms of the effectiveness that you saw the from the data, what can patients expect? Mantle cell lymphoma is not considered curable, and it's considered that they will probably still need therapy in the future. But in terms of deciding what to go to next, in terms of the sequencing question, is CAR T-cell therapy—and lisocabtagene maraleucel in particular—a good long-term option, generally, for patients with this particular subtype?

Flowers: Cellular therapies really have been a tremendous advance for all patients with lymphoma for where they've been approved. Mantle cell lymphoma is a very complex disease, because it's an incurable disease, but also because there are a variety of treatment options and treatment strategies. Some of the older strategies, historically, have been to give high-dose and intensive therapy, and then to follow that by an autologous transplant, and then to hope that patients have a very long remission from that first therapy, and then don't need another therapy for many years or maybe even decades. So, that's been one historical approach that's been pursued. We now have randomized data to suggest that that may not be necessary in the modern era.

Some other approaches, including approaches that had been led by my colleague, Michael Wong, [MD, of MD Anderson Cancer Center], have been to give less intensive therapy with targeted therapies as an upfront therapy, and then to follow that up with more prolonged maintenance therapy. So, that's another option for patients. But inevitably, patients relapse from therapies regardless of what we do for the majority of them. For patients who have relapse of their disease after therapy, CAR T cell now offers another form of a single therapy with a high response rate, and we will need to see over time how durable those responses are. But I think we've seen from other settings with CAR T-cell therapy that that can be meaningful and quite durable responses that really create great new options for patients.

References

1. Caffrey M. FDA approves liso-cel to treat R/R mantle cell lymphoma. AJMC^®. May 30, 2024. Accessed June 6, 2024. https://www.ajmc.com/view/fda-approves-liso-cel-to-treat-r-r-mantle-cell-lymphoma

2. Steinzor P. FDA grants accelerated approval for liso-cel for R/R follicular lymphoma. AJMC. May 16, 2021. Accessed May 30, 2024. https://www.ajmc.com/view/fda-grants-accelerated-approval-for-liso-cel-for-r-r-follicular-lymphoma

3. US Food and Drug Administration approves Bristol Myers Squibb's Breyanzi as a new CAR T cell therapy for relapsed or refractory mantle cell lymphoma. News release. Bristol Myers Squibb. May 30, 2024. Accessed May 30, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-as-a-New-CAR-T-Cell-Therapy-for-Relapsed-or-Refractory-Mantle-Cell-Lymphoma/default.aspx