Mark Wildgust, PhD, vice president, Global Medical Affairs, Oncology, Janssen, speaks on progression-free survival, complete response, and overall survival benefits observed with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 and other studies presented at the 63rd Annual American Society of Hematology Meeting and Exposition.
Findings presented at the 63rd Annual American Society of Hematology Meeting and Exposition (ASH 2021) on ciltacabtagene autoleucel (cilta-cel) showcase its potential as a transformational therapeutic option in multiple myeloma, with patient outcomes significantly improved vs standard-of-care or physician’s choice of therapy, said Mark Wildgust, PhD, vice president, Global Medical Affairs, Oncology, Janssen.
There are several studies being presented at ASH involving cilta-cel, including a meta-analysis of cilta-cel vs physician’s choice of therapy. What are the most significant findings on cilta-cel for relapsed/refractory patients with triple-class exposed multiple myeloma?
So, here at ASH, we're presenting the updated data from the cilta-cel phase 1b/2 study, where we now have up to 2 years worth of follow-up for the patients. But what we really see is that with longer follow-up, we still haven't reached the median progression-free survival [PFS] at 2 years. Actually at 2 years, the PFS is around 60%.
The question that you asked was really about, what does the data look like in terms of these meta-analyses that we have done and we're presenting, as well as the comparison vs the LocoMMotion study as well. From a clinical perspective, for myself, it's somewhat clear that the data that we're seeing from cilta-cel are transformational.
We're seeing a response rate of 98%; we're seeing a stringent CR [complete response] rate of 83% now at 2 years worth of follow-up. You don't even see that type of response rate or even stringent CR rate even with quad therapy, followed by transplant, followed by consolidation. But I think that it's a reasonable question, well, what does this look like vs standard-of-care?
When you think about standard-of-care for somebody who is refractory to their last line of therapy, is triple refractory, the outcomes for those patients are poor. So, from an equipoise perspective, you can't really do a randomized study of cilta-cel vs standard-of-care. One way we can address that is to take a look at real-world datasets, and that's exactly what we did.
We looked at data from Flatiron, from Mammoth. We looked at it from a number of other sources, even including our own data from daratumumab studies in terms of what they got later. What we see is a consistent benefit in terms of using cilta-cel instead of that kind of physician's choice in those late lines of therapy.
So, I think that gives us more confidence and confirmation that what we're seeing in the cilta-cel study, for the clinicians and scientists out there, it's somewhat apparent, it's transformational. I think that comparative data vs real-world data really just confirms that and kind of crosses a T and dots an I in many ways.
The use of CARTITUDE-1 data in comparison with LocoMMotion data represented a creative way to evaluate therapies that could offer guidance on the ability of cilta-cel to meet unmet needs in multiple myeloma. Can you speak on this abstract?
The data that we looked at, looking at cilta-cel vs the LocoMMotion study, I think is another piece of really trying to understand how does the cilta-cel data and the phase 1b/2 study look like vs standard-of-care. And I talked about just a few moments ago, the meta-analysis that we did.
Probably one of the most robust ways of looking at that is to really look at a prospective observational cohort, where you really are collecting in real time the data for what patients are getting. So, in that LocoMMotion study, it was enrolled in 9 countries in Europe and enrolled in the United States as well. The first thing that you look at when you look at the standards-of-care in that late lines of therapy, there were 91 different regimens used, which really shows you that there is no standard-of-care and that there's a real lack of treatment options, because really, physicians are trying anything they can, because we've run out of treatment.
What we saw when we looked at that LocoMMotion data, we saw between a 30% and 40% response rate, we saw a PFS of about 3 months, and an overall survival of between 9 and 12 months. So, the outcomes for that prospective observational cohort were poor.
In the presentation here at ASH, we're actually comparing now, in a propensity-matched way, really comparing side by side cilta-cel data vs that LocoMMotion data. You can kind of almost step up the quality of that type of work by looking at that prospective observational cohort. It was designed in a way where we could actually match the parameters and match the patients from LocoMMotion to the phase 1b/2 study, so we can really take patients that are like for like and make that type of comparison, again without randomizing patients where I think there will be concern from an equipoise perspective.
What we see is a hazard ratio of about 0.15 for PFS in favor of cilta-cel and a hazard ratio of 0.2 in terms of overall survival. So, you're seeing an 80% reduction in the risk of death with cilta-cel, and I think this is another data set that really confirms that I think what a lot of clinicians feel: that cilta-cel is really providing a transformational kind of step forward in terms of outcomes for patients.
What are some future considerations regarding cilta-cel after these findings presented at ASH?
I think with cilta-cel, one of the aspects that we're really starting to see now is that in those patients who are achieving a sustained minimal residual disease [MRD], or sustained kind of remission—and you'll see when Tom Martin, MD, presents those data—that the sustained MRD for 6 months or for 12 months really does suggest that those patients have really transformational outcomes in terms of PFS.
Median PFS of more than 2 years in this patient population is remarkable. Bear in mind, in LocoMMotion, it was 3 months and overall survival was 9 months. Here, you've got 60% of patients still progression free, 60% of them at 2 years. And then you start to then look at those individuals who had sustained MRD negativity. At 2 years, for those patients who had sustained MRD negativity for 6 months, you have a PFS of 92%, and those who had sustained MRD negativity for 12 months had 100% PFS.
So, I think the data are really starting to suggest that in those patients taking cilta-cel—those patients getting to that deep response, which we see are more than 80% getting stringent CRs—that the durability of response is really something perhaps that we have not seen before.
While the data look fantastic in the relapse setting, I think the most exciting piece now was when we go earlier in the lines of therapy. We’re excited with that with just opening up the CARTITUDE-5 study, which is our first study in the treatment-naive setting.