ASH 2021 | Understanding how patients relapse from CAR T-cell therapy
Yi Lin, MD, PhD, Mayo Clinic, Rochester, MN, describes mechanisms of relapse from chimeric antigen receptor (CAR) T-cell therapy. Bone marrow and blood samples were taken from patients before and after receiving CAR T-cell therapy and the differences in the cells of patients who relapsed early and patients who relapsed later were analyzed. Differences in myeloma cells, the number of cytotoxic CD8 T-cells cell, as well as the number of difference clonal subclusters were observed. The findings may reveal whether immunotherapy is a suitable option for certain patients post-CAR-T-cell therapy. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
I’d be happy to share the results of our studies in patients who had received various BCMA CAR-Ts for multiple myeloma. We now have the first CAR-T approved for standard of care practice. And so it’s really important now as we’ll use it more and more to understand when patients do relapse from this CAR-T, what are the mechanisms of relapse? So we can more rationally hopefully select the subsequent therapy and develop future therapies that will deepen the response...
I’d be happy to share the results of our studies in patients who had received various BCMA CAR-Ts for multiple myeloma. We now have the first CAR-T approved for standard of care practice. And so it’s really important now as we’ll use it more and more to understand when patients do relapse from this CAR-T, what are the mechanisms of relapse? So we can more rationally hopefully select the subsequent therapy and develop future therapies that will deepen the response.
So what we did was to look at both the myeloma cells and the immune cells in the bone marrow and the blood of 15 patients before they received CAR-T and also at the time of relapse. A group of them relapsed early within the first year and a subset of these patients relapsed much later over a year and a half. So we wanted to see if there are predictors at the time of CAR-T infusion or prior to CAR-T infusion that can identify patients who might have a longer response versus those who don’t.
And we did find that the myeloma cells had different characteristics between those who had early versus late response and that the T-cell profiles of the patient, particularly whether they had more CD8 cells with cytotoxic potentials were different in those patient populations. And then perhaps not surprisingly, at the time of relapse, those patients who relapsed early versus late had very different clonal subclusters of myeloma cells. So now we’re just trying to delve deeper into those characteristics to see if we can understand the type of myeloma cell that could be resistant to CAR T-cell therapy, and also the T-cell profiles or the T-cell compositions are quite different in patients relapse early versus late. And that may give us a clue in terms of is there more roles for subsequent immunotherapy directed approach at the time of relapse and CAR-T?
So we hope that… I also see there are other colleagues who look into these types of studies using multiomic deep sequencing studies. So I think we’re really moving forward as a field to try to improve CAR-T treatment in multiple myeloma.
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