COSTEM 2021 | TCR-based cell therapies for hematological malignancies
Michael Bishop, MD, University of Chicago, Chicago, IL, talks on the potential use of T-cell receptor (TCR)-based therapy for the treatment of hematological malignancies. Prof. Bishop argues that due to the availability of a large number of extracellular targets that can be used to design chimeric antigen receptor (CAR) T-cells, the utility and necessity of TCR-based therapies for lymphomas and myeloma is currently limited. In Prof. Bishop’s opinion, TCR-based therapy is more interesting in the field of solid tumours where there is a limited number of cell surface targets. This interview took place at the 6th Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM), which took place virtually.
Transcript (edited for clarity)
We’ve known that now for several years going on probably 10 years, that CD19-directed CAR-T cells are highly effective in patients who have failed, or I shouldn’t say patients, patients who have disease that has either failed to respond or progressed after two or more lines of therapy. And matter of fact, many of these patients have been multiply treated with far more than two more lines of therapy and that, and still had significant responses...
We’ve known that now for several years going on probably 10 years, that CD19-directed CAR-T cells are highly effective in patients who have failed, or I shouldn’t say patients, patients who have disease that has either failed to respond or progressed after two or more lines of therapy. And matter of fact, many of these patients have been multiply treated with far more than two more lines of therapy and that, and still had significant responses. And the hypothesis is, well, if we use this earlier in the disease course, would this be more efficacious? And particularly targeting a specific patient population of patients who have primary refractory disease to frontline therapy or rapidly recur after frontline therapy. And this disease population results have been relatively dismal with long-term survival as defined by greater than five years is less than 25%.
Now, the only caveat to this is you’re selecting out for an extremely aggressive patient population. So, with the hypothesis, if you use early, it might be better, may not apply because this is such a bad patient population. So, there have been three major trials that have addressed this and these results we are expecting to be, the results of will be reported at the upcoming 2021 annual meeting of the American Society of Hematology meetings, which will take place in Atlanta in December. And the three trials are ZUMA-7, which uses the Kite CD28-directed CD19 CAR with a 4-1BB costimulatory domain. And then there is TRANSFORM, which uses the BMS product, which is also an anti-CD19 with a 4-1BB, but with a balance of CD4s and CD8s. Now, we have only seen press releases on these three trials and two of the trials have demonstrated superiority of CARs over standard of care, which would be conventional chemotherapy and, and if chemosensitive autologous stem cell transplantation.
And one of the trials did not show any difference in event-free survival. All three trials’ primary endpoint was event-free survival. So, we’re going to have to look very carefully and compare these three trials, what their specific patient populations by trial design, they look to be relatively similar in terms of eligibility, but the trial designs are there are subtle differences between the three trials. It does appear that just based upon the preliminary small amount of data that’s been revealed so far that CAR-T cells are superior in this clinical situation. But I really think that we need to do a deep dive and a comparison so we can understand the biology of the disease and actually, specifically, identify if there are specific patient populations within that high risk populations, which benefit more or benefit less.
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