EBMT 2021 | Cellular therapy: changing clinical practice for treatment of myeloma

Cell therapy is clearly impacting in the management of patients with multiple myeloma. Today, through the inclusion of patients in clinical trials and tomorrow because this cell therapy will be available. And we know that BCMA CAR T-cells will be the first BCMA-targeted therapy, targeted cell therapy approved for patients with multiple myeloma.

Today, we have to restrict the use of BCMA-targeted therapy, and according of the potential label we have to select this therapy for relapse and refractory myeloma patients who are already exposed to the proteasome inhibitors in immunomodulatory drugs and anti-CD38 monoclonal antibodies. Personally, I consider that once the patients with myeloma have been already exposed to these three drug classes [inaudible], they can’t be received, they can be candidates to receive BCMA-targeted therapy, and it is not necessary the patients to receive all proteasome inhibitors, all IMiDs, and all anti-CD38 monoclonal antibodies.

The challenging situation in the near future will be how to select bispecific monoclonal antibodies versus BCMA CAR T-cells. I think that the challenging situation is a good situation. Definitely, we have to incorporate patient and disease-based factors in order to make it the right choice. And in principle, the chronological age is not going to be a factor driving the choice for both approaches. So, therapy patients have to present a good performance status, with a good organ function, with a good bone marrow reserve, but maybe we can consider a frail population or myeloma patients, more frail, will be more candidates to receive bispecific monoclonal antibodies because definitely this strategy, this approach of therapy, is off-the-shelf and it basically does not require hospitalization except for the administration of the first dose.

But I think that one important driver, in order to make the right choice, would be the aggressiveness of the disease. And if the patient is in front of us with a very aggressive disease, with unnamed component duplicating every week, this patient should be a candidate in principle for bispecific monoclonal antibodies, because today the vein-to-vein in the CAR T-cell approach is of approximately eight weeks. If we decide to offer this option for these patient with a very aggressive relapse, maybe the patient could not arrive to receive the CAR-T. But again, this is when these options of therapy are going to be available at a late advanced stage of the disease. The next step is definitely to move them to earlier lines of therapy. And we have a right now the possibility of including our patients in Phase I, II, or even Phase III clinical studies in relapsed and refractory myeloma patients after one to three prior lines of therapy, and even some patients in the upfront setting.

There are some clinical studies evaluating the role of CAR T-cells in high-risk group of patients after the first line of therapy. Even the results of these clinical studies are positive. I think that we will be in a right position in order to offer all these third therapies earlier on to our patients with multiple myeloma in principle and first in patients with high-risk features. And of course, the second step is to offer these approaches to a standard-risk patients. I think that we will be able to offer very long progression-free survival, and definitely very long overall survival to our patients with multiple myeloma. And why not, maybe we can consider that our dream about the cure of multiple myeloma will be a reality with these novel cell therapy approaches.