COMy 2023 | Moving away from alloSCT to cellular therapy in multiple myeloma: current and future outlooks
Hermann Einsele, MD, FRCP, University of Würzburg, Würzburg, Germany, comments on the current shift from allogeneic stem cell transplantation (alloSCT) to CAR-T cell and bispecific antibody (BsAb) therapy in patients with multiple myeloma. Prof. Einsele discusses the progression from alloSCT to cellular therapies and the associated improvements in patient outcomes, and further notes that though CAR-T cells result in more complete remissions than alloSCT, the data on CAR-T cells is not yet robust enough to compare progression-free survival (PFS) across the modalities. This interview took place at the 9th World Congress on Controversies in Multiple Myeloma (COMy) 2023, held in Paris, France.
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Transcript (edited for clarity)
That was a very challenging topic because allogeneic stem cell transplantation was very intensively used about 20/30 years ago when it was the only curative treatment that we had for patients with multiple myeloma and it was the first step towards immunotherapy. So a lot of people use it, but it has two, kind of, parts. It has on one part the graft-versus-myeloma effect. So you have a very high, very intensive anti-myeloma activity...
That was a very challenging topic because allogeneic stem cell transplantation was very intensively used about 20/30 years ago when it was the only curative treatment that we had for patients with multiple myeloma and it was the first step towards immunotherapy. So a lot of people use it, but it has two, kind of, parts. It has on one part the graft-versus-myeloma effect. So you have a very high, very intensive anti-myeloma activity. But on the other hand, it’s quite often associated with graft-versus-host disease, which is very much interfering with patients’ quality of life. And so there was a lot of issues about how can we separate the positive graft-versus-myeloma effect from the negative graft-versus-host effect. And I think this problem is still not really solved, but it kind of induces a lot of activities around cellular therapy because we realized that myeloma is a disease which can be immunologically controlled. So the idea was what can we do to improve the patient’s own immune system towards the tumor? And there were two strategies. One is CAR-T cells, the other one is bispecific antibodies by which we increase the frequency of tumor reactive T-cells considerably. And in my talk I compared the outcome of allogeneic stem cell transplantation with CAR-T cell therapy. And what we learned is that with CAR-T cell therapy we can induce much higher responses, much more complete remissions when compared to allogeneic stem cell transplantation. But we don’t really can compare yet is progression-free survival because the follow-up for patients after after CAR-T cell therapy is just not sufficient. But we can also learn from allogeneic stem cell transplantation because we show that the earlier we apply it, the more effective it can be. And that’s the same now for CAR-T cell therapy that we move CAR-T cell therapy to earlier lines of therapy and we potentially combine it with other drugs that improve the persistence of CAR-T cells. So I think there are two modalities. The newer one is clearly CAR-T cells. It’s more effective. It’s probably also quite less toxic because we have a very low mortality now, low early morbidity of CAR-T cell therapy. So I think the tendency is clearly that we move away from allogeneic stem cell transplantation but towards CAR-T cell therapy and bispecific antibodies.
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