EBMT 2022 | The impact of the approval of cilta-cel in multiple myeloma

CAR-T represents a true revolution in hematology, but I’m convinced they will also be used in solid tumors. And when we look over the last five years, we started with autologous CAR-Ts in pediatric and young adults, acute lymphoblastic leukemia being approved first. Then we have the anti-CD19 autologous CAR-T approved in lymphomas, and initially it was DLBCL, but later on, we had mantle cell lymphoma, follicular lymphomas, and other entities. And more recently, actually, we had CAR-T approved in multiple myeloma, in relapsed/refractory multiple myeloma. The first product and construct was the ide-cel product, which was approved by the FDA in 2021 based on the KarMMa trial. But very recently, actually, early March 2022, we’ve seen the approval by the FDA of another construct, a different construct, namely cilta-cel. And both ide-cel and cilta-cel are targeting BCMA as an antigen, the B-cell maturation antigen, which is really a very attractive candidate when it comes to multiple myeloma.

What’s really interesting is about the results achieved with cilta-cel, and this is based on the CARTITUDE-1 trial, 97 patients if I remember well, highly advanced relapsed/refractory patients who received a median of six lines of prior therapies, including a significant proportion of patient who are triple-class exposed, triple-class refractory, penta-drug exposed, penta-drug refractory. And despite being in such an advanced status, actually the response rate is quite impressive, up to 98%, including more than 80% stringent CR. And such high level of response rate is going to translate despite a relatively short follow-up into a clear advantage in terms of progression-free survival, because we are roughly a little bit less than two years of median PFS in the whole population. And this has not yet reached the median PFS in the patient to achieve the stringent CR.

So I think the arrival, the approval, of this new CAR-T construct cilta-cel in multiple myeloma is going to add and to bring a lot of added value to the other available options, the different drugs, the different antibodies, but also the other CAR-T construct, ide-cel, which is already approved and will allow, I think, the myeloma community to further improve the outcome of these relapse refractory patient. But in my opinion, it will not take long before these CAR-Ts are going to be used in earlier lines of treatment, similar to what we have seen actually in lymphomas. And we already know that there are trials comparing traditional combinations in myeloma versus CAR-T or even challenging autologous transplant with CAR-T. So this is a really very exciting era for all of us involved in the myeloma field.