We did a pooled analysis of all the MagnetisMM studies; so, there are four studies that enrolled relapsed/refractory multiple myeloma patients. What this pooled analysis was about was trying to look at who the BCMA-refractory patients or BCMA-exposed patients are previously. They could have received a BCMA CAR T, BCMA antibody-drug conjugate in the past. Now, re-exposure to a BCMA-targeted bispecific antibody, would that have any impact or would that result in response? This is the question that was asked.
The second part of the question was how safe is it? Are they at increased risk of infections? What were the rates of CRS, what were the rates of ICANS? All these questions were addressed in this specific trial.
The study design involved a pooled analysis of four different trials: the MagnetisMM-1 trial, the MagnetisMM-9 trial. Different trials had different designs but one common unifying feature is the relapsed/refractory multiple myeloma patients that were enrolled on these trials that have received a BCMA-targeted therapy and they also have received a prior BCMA-targeted therapy.
So we identified close to 89 patients that fit this criteria across all these four different trials. When you look at these 89 patients, a major fraction, around 59 patients, received ADC alone. It’s a BCMA-targeted antibody-drug conjugate. Close to 40 of them had received a prior CAR T which was BCMA-directed therapy. So the median age is younger for those patients who received a CAR T, which is expected because these are the young, fit patients. What is very unique about the characteristics of these patients were these are heavily refractory patient populations. So those patients that received a prior ADC had eight prior lines of therapy; those patients that received a prior CAR T had seven prior lines of therapy. So this is a heavily refracted patient population.
If you start breaking down by how many lines of therapy they have seen, what is the refractoriness or refractory status? Around 55% in each of these arms were penta-refractory, that means they have seen two prior IMiDs, two prior PIs and one CD38 antibody. If you break it down further, around 39% of the patients were hexa-refractory, this is a new statement where these patients had seen, in addition to the five I described, these patients had seen a prior BCMA-targeted therapy as well. So this is a new group of patients, we don’t know what the standard of care for these patients is. How do these patients do, what is the natural history going to be? We don’t know any of those. So that is where this trial really helps us to see what the benchmarks are, what can we expect in terms of responses for these patient populations?
We were able to see response rates, an overall response rate, of close to 46% of the patients. So patients who had a prior CAR T had a 52% response rate. Patients who had a prior ADC, their response is slightly lesser. In terms of the duration of the responses, these duration of responses among the patients that were responding, they continued to derive much, much long-term responses beyond the one year mark, 1½ year mark.
If you look at the PFS, the PFS for this entire cohort is 5.5 months. So there are drugs that were approved in myeloma that we use now which have a PFS of less than 3 months. So this is very helpful for us to understand that you can re-challenge these drugs in patients who had seen prior BCMA-targeted therapies. More importantly, the biggest question that comes to our minds is does it increase the risk of infection risk? Because that’s one common theme that we are seeing nowadays with all these BCMA-targeted therapies. So this pooled analysis did not show that there was an increased risk of infections; it did not show there was any increased risk of CRS compared to what is expected for the baseline. It did not show there is an increased risk of ICANS so it’s a win-win. Yes, you’ve found a benchmark in terms of the efficacy, you’ve found a benchmark in terms of the CRS, ICANS, infections. So this is a potential option for these BCMA refractory patients, the new hexa-refractory patient population.
What will be the clinical impact of these results?
The post-BCMA space is the new post-CD38 space. So we need new treatment options; fortunately we have targets, we have targets like the GPRC5D, we have CRH5. An additional option is this is an extra option for the patients to receive a BCMA-targeted therapy for those patients that were in the post-BCMA space.
