Noopur Raje, MD
The deep and durable responses observed with the anti-BCMA chimeric antigen receptor (CAR) T-cell therapy bb2121 suggest that the novel treatment could be a significant addition to the armamentarium, according to Noopur Raje, MD.
Raje, who is lead author of the phase I CRB-401 study of bb2121, said the encouraging data have led to the ongoing phase II trial, which is still accruing patients (NCT03361748). A similar patient population will be tested in this portion of the study.
“Given that we are seeing stringent responses in patients who are minimal residual disease (MRD) negative—which we never would have expected to see in a patient population that was as refractory as it was—it’s really encouraging,” said Raje.
Data from the CRB-401 trial showed bb2121 was associated with a 95.5% overall response rate. Moreover, it induced a progression-free survival (PFS) of 11.8 months, with a median duration of response of 10.8 months.
While CAR T-cell therapy has shown promise, there is still a need for treatment that caters to narrower patient populations. Recent data suggest that selinexor, an emerging novel agent, could address this issue. Based on results from the phase IIb STORM trial, a rolling submission of an FDA new drug application was completed for selinexor in August 2018.
In an interview with OncLive
, Raje, director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, discussed the latest treatment advances in multiple myeloma.
OncLive: Do you have any update for the ongoing phase II study with bb2121?
: We have seen the phase I data, which were recently presented. These data obviously looked very promising, which is what prompted the phase II study. We haven't seen any data yet from the phase II study, but I know that it's rapidly accruing. The trial started accruing only at the beginning of this year, and we're almost halfway through completely accruing for this trial. The hope is that we will meet our goal before the end of the year. As far as efficacy, we'll just have to wait and see.
What impact could bb2121 have on the treatment landscape?
It [would be] a really important addition to the armamentarium we already have. Given that we're seeing stringent responses in patients who are MRD negative—which we would have never expected to see in a patient population that was as refractory as it was in the phase I trial—it's really encouraging. The fact that we're seeing a PFS of close to 1 year in this heavily pretreated penta-refractory patient population with more than 7 prior lines of treatment—it's not what we imagined. For us to also have seen not that much toxicity was actually really reassuring. We're seeing patients who were MRD negative with a PFS of more than 17 months. These data are really incredible. We're all very excited.
The hope was that CAR T cells would cure multiple myeloma. But, now we have to be a little bit realistic. The problem with our expectations is that we've taken patients who really had no other options for treatment. Therefore, in my mind, these are still encouraging results. What impact will this have on the future of treatment? It's still a proof-of-principle study, which has shown responses—durable responses—with very little toxicity. The next step would be to move it to an earlier phase of treatment so that you can actually translate these responses into long-term disease control.
There have been some interesting data with triplet and quadruplet combinations. When does this play a role?
As of right now, it doesn't affect our practice because it's being used in the relapsed/refractory space. The triplet combinations are obviously better than doublets; that has been proven. In most places in myeloma, we're using triplets. I've always been an advocate of that. We're now starting quadruplets in the upfront setting, which is going to be very important. Along with these quadruplets, we are using MRD testing as an endpoint to either escalate or de-escalate treatment. By doing so with advances in technology and therapy, we may actually be curing a subset of patients with these treatments we have available already.