CAR-T Cell Therapy for Relapsed, Refractory Mantle Cell Lymphoma Fills Unmet Need

Treatment with CAR-T cell therapy Breyanzi (lisocabtagene maraleucel; liso-cel) now opens up options for patients with relapsed or refractory mantle cell lymphoma (MCL), following the Food and Drug Administration’s (FDA) approval in late May.

Of note, patients with relapsed or refractory MCL who have certain mutations, such as TP53 mutations, typically have poorer prognostic factors, Dr. Gwen Nichols, chief medical officer at The Leukemia & Lymphoma Society, said during an interview with CURE®. Having poorer prognostic factors means patients have a lower chance of responding well to treatment, as defined by the National Cancer Institute.

However, data from the trial that supported the approval of Breyanzi showed that patients with poorer prognostic factors demonstrated responses to the drug, Nichols said.

Traditional Treatments for Relapsed or Refractory MCL

For patients with relapsed or refractory MCL, traditional treatment was a Bruton tyrosine kinase (BTK) inhibitor, Nichols explained. A BTK inhibitor is a drug that blocks the BTK protein, which is found on certain cancer cells and prevents these cancer cells from growing, according to the National Cancer Institute.

“This [approval of Breyanzi] is for patients who have already had a BTK inhibitor, which is the most common first or second treatment of mantle cell lymphoma and can be very effective,” Nichols said. “So, when people relapse after they've been on a BTK inhibitor, the doctors don't have a long list of great treatments they know will work. So this is really very promising from that point of view — that this is not a brand new population.”

In the TRANSCEND NHL 001 clinical trial, patients with relapsed or refractory MCL must have received at least two prior lines of treatment, which included a BTK inhibitor. Researchers on the trial found that 85.3% of patients responded to Breyanzi and 67.6% of patients experienced a complete response (showing no signs or symptoms of cancer), according to Bristol Myers Squibb, the manufacturer of Breyanzi.

“The total patient number was 68 patients, so it's not hundreds and hundreds, nor will it ever be in this disease,” Nichols said. “But that being said, they included patients that had TP53 mutations, which has a poor prognostic factor, so that is also very helpful because it wasn't like all the patients [had] really good prognoses.

“Now these patients who had bad prognostic factors responded, so while the numbers are small, I think the population was representative of the struggles people have after they've relapsed with mantle cell lymphoma.”

Unmet Needs Breyanzi Addresses and Unmet Needs that Persist in MCL

A large unmet need in relapsed or refractory MCL is the time patients will stay in remission, Nichols noted.

“Each time [patients] get another subsequent therapy, it is likely that [their] response time — the time that [they’ll] stay in remission — will be shorter than whatever their first remission was,” she said.

For instance, Nichols explained, if a patient who was treated with a BTK inhibitor stayed in remission for two years and then received a chemotherapy regimen, their remission will likely last for less than two years. After each line of therapy, she emphasized that the treatments won’t work as effectively.

But with CAR-T cell therapy, Nichols said that “using the immune system may change that paradigm,” which helps address this unmet need in relapsed and refractory MCL.

“[In the trial, patients’] the median time for responses to last was [approximately] 13 months, so it was more than a year,” she said. “If [patients did not respond well to] prior therapies, that’s a very good length of time.”

Nevertheless, “we still have work to do,” Nichols said, notably because not every patient shows a complete response to treatment.

“[Breyanzi] is a great therapy, we need to find out [if] there [are] people who respond particularly well,” she said. “Would it be better to use this therapy for those patients earlier? Would they get a longer response if we did that? Or can [doctors] give this therapy again a few years later and [patients will] still respond? These are still unknowns.”

Managing Costs While Receiving Breyanzi

As patients receive Breyanzi for their relapsed or refractory MCL, the expenses of treatment or traveling may become a challenge, Nichols said.

Starting the process of receiving CAR-T cell therapy involves collecting T-cells (immune cells) from the patient to produce the therapy. This process takes several trips to the respective treatment center, Nichols mentioned, which can become expensive if patients live far away from the center.

“[For] someone who lives hundreds of miles away, that means staying overnight, it often means having someone with [the patient] when [they’re] doing this,” she explained. “It can be a big undertaking because … [patients] have to get therapy to stimulate [their] T cells, [they’ll] have to come in and have [their] T cells collected, modified, get the T cells infused and to be observed for a few days. So, it's quite a lot of back and forth, if you don't live close to where the treatment is being given.”

To ease this travel burden, Nichols recommended patients take advantage of available resources from both The Leukemia & Lymphoma Society and Bristol Myers Squibb. Programs, such as the patient travel assistance program from The Leukemia & Lymphoma Society.

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