IMW 2021 | Replacing ASCT: CAR-T or bispecific antibodies?
Parameswaran Hari, MD, MRCP, MS, of the Froedtert Hospital Cancer Center, Milwaukee, WI, discusses whether chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibodies (BsAbs) could be a replacement for autologous stem cell transplantation (ASCT) for the treatment of multiple myeloma, and shares insights into the drawbacks of each of these therapies. Whilst both techniques can produce significant responses in patients with myeloma, even in those with relapsed/refractory myeloma, patients often relapse after receiving CAR-T therapy, which is administered in one dose. In contrast, BsAbs are repeatedly administered to maintain a response, and present less toxicity than CAR-T therapy. Dr Hari suggests that as both techniques have their drawbacks it must be questioned whether these methods of treatment will fully replace ASCT, or if they can be advantageous when used alongside ASCT in the treatment of myeloma. This interview took place during the 18th International Myeloma Workshop (IMW 2021) congress.
Transcript (edited for clarity)
I’m speaking to you on the background of the International Myeloma Workshop in Vienna in September, 2021. I will be participating in a debate here on which immune approach in myeloma is most likely going to replace autologous stem cell transplant.
So, there are two major immune approaches in multiple myeloma that are emerging as blockbuster treatments for patients. These are, one, CAR-T cells against BCMA, and the other approach is bispecific antibodies, which are generally a BCMA-CD3 bispecific antibody in the category of teclistamab or TNB-383B, et cetera...
I’m speaking to you on the background of the International Myeloma Workshop in Vienna in September, 2021. I will be participating in a debate here on which immune approach in myeloma is most likely going to replace autologous stem cell transplant.
So, there are two major immune approaches in multiple myeloma that are emerging as blockbuster treatments for patients. These are, one, CAR-T cells against BCMA, and the other approach is bispecific antibodies, which are generally a BCMA-CD3 bispecific antibody in the category of teclistamab or TNB-383B, et cetera. Both of these are capable of producing a large number of responses, even in relapse/refractory myeloma patients, and sustaining those responses over time.
However, there are fundamental differences between the two approaches. CAR T-cells are tedious. They are generally a one-and-done approach, where one treatment similar to a transplant is done, and further maintenance strategies have not, at least at this time, emerged. And following that, the majority of patients get to a MRD-negative remission, and those patients tend to keep those remissions going for anywhere from 1 to 2 years, or even beyond, in some cases, especially for the exceptional responders. We don’t know the mechanisms of relapse very clearly after CAR T-cells.
The bispecific antibodies on the other hand are even similar to any other monoclonal antibody treatment, such as daratumumab or Sarclisa or isatuximab. These treatments are repeatedly given at an interval ranging from every three weeks to every week. And their side effect profile, at least for the initial part, is similar to CAR-T, but at the lesser grade of severity, but the repeat treatment can go on for many years, as long as the patient is responding.
Both of these approaches have their own risks and benefits, and also, we need to ask the question, do they replace autologous stem cell transplant? Do they compliment autologous stem cell transplant? Could they be used to consolidate the benefit of autologous transplant? And how will myeloma initial therapy change in the future? Because all of these immune approaches right now are being tested in relapse patients, and the treatment of patients who have never relapsed or at the upfront treatment, how we use auto-transplant generally, that setting immunotherapy is still in its early, early stages.
So, overall, I think it’s going to be an exciting debate and I request anyone who’s in Vienna or following online to log into it. Myself and Dr Hermann Einsele will be debating each other about which approach serves patients the best in the future.
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