Liso-Cel Shows Encouraging Clinical Activity, Safety in Relapsed/Refractory MCL

Lisocabtagene maraleucel (Breyanzi; liso-cel) demonstrated promising clinical activity and was associated with a low incidence of grade 3 or higher cytokine release syndrome (CRS) or neurological effects (NEs) in patients with relapsed/refractory mantle cell lymphoma (MCL), according to data from the phase 1 TRANSCEND-NHL-001 trial (NCT02631044) presented during the 2020 ASH Annual Meeting & Exposition.¹ 

“MCL is a difficult-to treat-disease—particularly for certain categories of patients, such as those who are refractory to BTK inhibitors; those who have very high-risk histology, like those with p53 mutations; or those who are pleomorphic or have blastoid morphology,” M. Lia Palomba, MD, said.

Among the 32 patients included in the study, lisocabtagene maraleucel elicited an overall response rate of 84% (n = 27), with 59% (n = 19) experiencing a complete response. In terms of safety, 18 patients (56%) experienced serious treatment-emergent adverse effects (TEAEs) and 27 patients (84%) reported grade 3 or higher TEAEs. The most common TEAEs included neutropenia (41%), anemia (34%), and thrombocytopenia (31%). Additionally, 16 patients experienced CRS, while 9 patients had NEs.

In an interview with OncLive^®, Palomba, a medical oncologist at Memorial Sloan Kettering Cancer Center, discussed the data from the TRANSCEND-NHL-001 trial and projected how lisocabtagene maraleucel could fit into the treatment paradigm for patients with MCL. 

OncLive^®: How does liso-cel compare with other products like brexucabtagene autoleucel (Tecartus; formerly KTE-X19)?

Palomba: It is not fair to compare them because, obviously, the follow-up in this particular study is much shorter. The only thing that appears to be a real difference between the studies is the toxicity. This particular product seems, in general, to have a lower toxicity than the 2 approved products for diffuse large B-cell lymphoma or KTE-X19 for MCL. That is the only thing we can say right now. We can’t compare efficacy in any way.

What efficacy data were observed with liso-cel in the TRANSCEND-NHL-001 study?

We saw an overall response rate of 84%, and a complete response rate of 59% in patients [with MCL]. We have a few patients who have reached the end of study who are in complete remission. The study completed at 2 years, so that was very successful.

Additionally, we have seen responses in central nervous system [CNS] involvement. Of the patients [for whom] I presented [data for] at ASH 2020, only 1 had CNS involvement and had a response. After the data cut off, a few more patients with CNS involvement were enrolled, and we have seen responses there. That is extremely encouraging, because those patients are the most difficult to treat and usually have a very short survival.

Could you expand on the safety observed with the agent?

About half of the patients [enrolled in the study] had [occurrence] of CRS of any grade, but only 1 patient experienced a grade 3 effect. In terms of neurotoxicity, about 34% of the patients had any-grade neurotoxicity, with only 4 patients developing a grade 3 or higher case.

Additionally, [we’re seeing these toxicities quite early]; they occur on [approximately] day 8. However, [these effects] do seem to be resolve very quickly: on average, 4 days after onset for CRS and approximately 8 days for neurological effects. Also, the rate of infections was quite low. That was unexpected, considering the fact that the patients were usually heavily pretreated and had received BTK inhibitors, for instance. We didn't see increased rates of fungal infections. We saw a grade 5 fungal infection, but it was only 1 case.

The product has shown to be very effective, with a low incidence of CRS and neurotoxicity. That might have to do with the costimulatory domain, which, in this case, is 4-1BB. Also, this product is given at a 1:1 ratio of CD4-positive and CD8-positive T cells, and that might have a little bit of an influence on the toxicity profile.

What are next steps for this research?

The next step is to wait for the data to mature. We have to prove that these responses are durable, so waiting 1 year or 2 to see whether we can prove that, would be wonderful. So far, we have proven that CAR T-cell therapy is a valid option for patients with MCL, and we also know from the data that patients who didn't require a breach in therapy did a little bit better. As such, having less disease on board or having controlled disease prior to receiving the product is important. Maybe it is necessary to bring this therapy earlier in the sequence of therapy for these patients.

Thinking further down the line, how do you foresee choosing between brexucabtagene autoleucel and lisocabtagene maraleucel? What factors will likely be considered?

Obviously, if one [product] is better than the other, it becomes clear which should be used. I can't say whether one will be better than the other, but in terms of toxicity, there is a definite difference. If we can select patients based on their comorbidities, or extent of disease at the time of referral, all those [factors will play a part in] how we select a product for a certain patient.

Reference

1. Palomba ML, Gordon LI, Siddiqi T, et al. Safety and preliminary efficacy in patients with relapsed/refractory mantle cell lymphoma receiving lisocabtagene maraleucel in Transcend NHL 001. Blood. 2020;136(supp 1):10-11. doi:10.1182/blood-2020-136158