麻豆传媒

An enriched chimeric antigen receptor (CAR) T-cell therapy called bb21217 improved responses and prolonged duration of response compared with non-enriched CAR T cells in patients with relapsed/refractory multiple myeloma, according to results of a phase I study presented at December's American Society of Hematology (ASH) virtual meeting.

In this exclusive 麻豆传媒 video, lead author , of Moffitt Cancer Center in Tampa, Florida, discusses the data from .

Following is a transcript of her remarks:

This was a phase I study using a compound that is called bb21217. This is a CAR-T directed against BCMA, or B-cell maturation antigen, a protein that is expressed preferentially in the myeloma cells. bb21217 uses the same CAR-T as bb2121, which is like the parent compound, except that these cells are cultured with a PI3 kinase inhibitor 07 -- that's where the name bb21217 comes from. And this PI3 kinase inhibitor, when you culture the cells, they are enriched for T cells that express a memory-like phenotype. And what this means is that these cells are not very differentiated, and the hypothesis is that if you do that, you can make these CAR T cells persist and function for longer. So, the preclinical data show that if you take cells from myeloma donors and you culture those cells with PI3 kinase inhibitor, that you enrich for the cells expressing memory-like T-cell phenotype.

And so this study was done. It was a phase I study with dose escalations 3 by 3, and then at the expansion the recommended phase II dose was 450. And what we presented was 69 patients who had been infused by the cutoff of the data. The median follow-up was about 6 months, so it's a study that is still early. And actually the median follow-up for the group that was recommended phase II was only 4 months, and some of the patients only have been infused one month prior to the cutoff.

So when looking at the safety, the toxicities are very manageable. By far the most common toxicities are cytopenias having low counts, which the majority of the patients recover quickly, but some patients did have prolonged cytopenias like we have seen with other CARs. We also see cytokine release syndrome, but again, the majority are actually grade 1 and 2, and the same with neurotoxicity. We have seen three deaths associated with adverse events. One patient died from an infection, fungal pneumonia, in the absence of myeloma progression. And then there were two patients who died secondary to cytokine release syndrome.

In terms of response, at the cutoff of these data, there were 59 patients who were evaluated for a response. And the response rate is 68%, with 29% of the patients achieving a complete remission. And of those patients who achieve a response, either a partial response or a complete remission, the majority were actually minimal residual disease negative.

There were some preclinical translational studies done to look and see if indeed we were enriching for this T-cell phenotype in the cells that we collected from the patients compared to the drug product. And that was confirmed, that enrichment was confirmed, and also peak expansion. So, in other words, when you give the cells to the patient, you know how the cells expand and also how long those cells persist. In other CAR-T studies, for example, using bb2121, the persistence of the cells at 12 months was about 20%. In our study, it was about 57%, and even at 24 months in those patients who were tested, we saw persistence.

We need more time to evaluate these patients, because obviously some of the patients, they just got infused. But it's very encouraging to see that proof of principle ... when we were seeing that enrichment for memory-like T cells, and hopefully we are going to see that that's going to translate to better responses and duration of responses.

Talking about duration of responses, we also see a median duration of response among all-comers of 17 months, which is encouraging as well, given median duration of response reported with bb2121 being about 11 months. The data are still early. We need more time to confirm these results, but it's definitely very encouraging.

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