First CAR T-cell Tx for Mantle Cell Lymphoma Fills Unmet Need

The US Meals and Drug Administration (FDA) granted accelerated approval on July 24, 2020, for the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (Tecartus) for the therapy of adults with relapsed or refractory mantle cell lymphoma (MCL). Medscape reached out to lymphoma specialist Ann S. LaCasce, MD, MMSc, to discuss what brexucabtagene autoleucel, the principle FDA-authorized CAR T-cell therapy for MCL, can also mean for the therapy of patients. LaCasce is an affiliate professor of treatment at Harvard Scientific School, Boston, Massachusetts, and director of the Dana-Farber/Mass Traditional Brigham Fellowship in hematology/oncology. This interview has been edited for dimension and clarity.

Medscape: What’s the critical takeaway from the ZUMA-2 trial, which ended in the approval of the CAR T-cell therapy brexucabtagene autoleucel?

Dr Lacasce: Brexucabtagene autoleucel is an exhilarating option for our patients with relapsed or refractory MCL. For of us that development after Bruton tyrosine kinase (BTK) inhibitors, our alternate choices till this time secure been restricted. The response rates and length of response up to now, albeit with rapid prepare-up, are very encouraging and must lead to long-time frame illness preserve watch over in a subset of patients.

Brexucabtagene autoleucel carries a black box warning for potentially fatal cytokine starting up syndrome (CRS) and neurologic toxicities. Can you elaborate on these aspect results and how they’re managed? When stop these negative results generally seem?

CRS and neurotoxicity are total and very a connected to what has been seen with axicabtagene ciloleucel in diffuse big B-cell lymphoma.

In ZUMA-2, the median time to onset of CRS was 2 days. Although extra than 90% of patients developed CRS, grade 3/4 befell in handiest 15% of patients. Supportive care and tociluzumab are the mainstays of therapy for CRS, with steroids feeble in increased-grade events. All events resolved within a median of 11 days.

Almost about neurotoxicity, this befell in 63% of patients, with grade 3/4 in 31% of patients. The median onset was 7 days, with a median length of 12 days. Neurotoxicity is managed with steroids. Patients also receive prophylactic antiseizure medications and shut recount.

Brexucabtagene autoleucel is authorized with a risk review and mitigation technique. What does this entail?

As with the CAR-T products authorized in aggressive lymphoma and acute lymphoblastic leukemia, all suppliers must whole risk review and mitigation technique coaching. This comprises scoring 100% on a prepare-up test to construct certain they’re intimately familiar with the administration of CRS and neurotoxicity, which may also be lifestyles threatening.

Where does brexucabtagene autoleucel slot within the therapy paradigm for MCL?

At this point, the therapy will most definitely be largely within the third line, after preliminary chemoimmunotherapy with or without autologous transplant followed by BTK inhibitor therapy.

A subset of patients are receiving up-front therapy with BTK and chemoimmunotherapy within the context of scientific trials. These patients will likely receive brexucabtagene within the 2nd line.

For patients with TP53 mutation/17p deletion, stem cell transplant and per chance chemoimmunotherapy stop now not provide enough illness preserve watch over. In some unspecified time in the future, these patients can also receive CAR-T earlier all over therapy, nevertheless scientific trials will must question this ability.

Can you commentary on about a of the good substances of this therapy, including the worth of incorporating it into scientific prepare?

As with any patients being belief to be for CAR-T therapy, one main field is timing and whether or now not patients will require bridging therapy, which, in our “real-world” skills with diffuse big B-cell lymphoma, has been connected with unhealthy outcomes.

These therapies are very pricey and require in truth supreme teams on the therapy amenities for apheresis and administration. To boot to, having effectively-skilled workers to preserve watch over toxicities is extreme. Charges will must be negotiated with insurance and therapy amenities.

Are varied CAR T-cell therapies being developed for MCL?

There are a fashion of latest strategies, including allogeneic or “off-the-shelf” CAR-T therapy, which constructs targeting a pair of cell surface proteins. Though tranquil early in fashion, this ability and skills will proceed to make stronger.

How can also ZUMA-2 have an effect on future scientific trials for MCL therapies?

The new unmet need will heart of attention on patients who relapse after CAR T-cell therapy. If the progression-free survival curves halt steady, fewer patients will need extra therapy. Having CAR-T readily available can also furthermore lower the employ of up-front stem cell transplant, as suppliers would know that an efficient technique exists for relapsed patients.

LaCasce has disclosed no connected financial relationships.

Kate O’Rourke is a freelance author in Portland, Maine. She has lined the sphere of oncology for over 10 years.

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