Key Takeaways
1. Improved MRD Negativity: Cilta-cel significantly increased MRD negativity rates compared to standard-of-care treatments.
2. Sustained Responses and Survival Benefits: Patients achieving deep MRD negativity with cilta-cel had longer-lasting responses and improved overall survival.
3. Potential Biological Factors: The study identified potential biological factors, such as lower inflammatory phenotype and better CAR-T manufacturing, that may contribute to the improved outcomes seen with cilta-cel.
Rakesh Popat: The purpose of this analysis was to look at the levels of minimal residual disease (MRD) for patients who received cilta-cel, which is a BCMA-targeted CAR T-cell, compared to the standard of care treatments that were available in the CARTITUDE-4 study. This was for patients who'd had relapsed myeloma between 1-to-3 prior lines and were then len-refractory. The key point is that overall, the MRD negativity rates at 10-5 was significantly higher compared to standard of care. What I thought was really interesting was that, if you look at the 10-6 level, which shows an even more in-depth analysis, that pretty much all the patients who achieved MRD negativity at 10-5 achieved MRD negativity at 10-6 cilta-cel. But that was not the case with the standard of care, where these patients were not achieving that same degree of depth of response. What we're also finding is a strong correlation with sustained MRD negativity complete response (CR). These are patients who are MRD negative and in CR at a time point of 12 months or more. There's a strong correlation with both progression free survival (PFS) and overall survival (OS). We see more patients who are able to achieve that with cilta-cel, and we also see that these patients were doing better in terms of survival.
Pharmacy Times: Given the significant improvement in MRD negativity rates with cilta-cel, how do you envision this impacting the treatment landscape for patients with lenalidomide (len)-refractory multiple myeloma?
Popat: So essentially, what this data is showing is that if a patient with len-refractory myeloma and early relapse receives cilta-cel, then they will be having a very deep response, which correlates to a strong PFS and OS. Essentially, what we're saying is that this is now a valid treatment option for patients as early as second relapse onwards and can be an alternative compared to the standard treatments that may otherwise be available. This should be a treatment that patients should be counseled for and to be considered at this stage.
Pharmacy Times: Could you briefly elaborate on some of the potential biological factors contributing to these results? How are these different or similar to other studies?
Popat: What was really interesting about this study was that we were able to correlate the levels of MRD negativity and sustained MRD negativity with a couple of biological end points. Essentially, what we find is that those patients who had a lower inflammatory phenotype, those patients who had a better CAR-T manufacturing phenotype, so these are patients with more effector memory cells, those patients who had a bigger CAR-T-expansion and those patients who had a lower soluble BCMA had a better outcome. What this is suggesting is that you can try and discern what are the best patients to receive CAR T-cell therapy looking at these biological phenotypes.
Pharmacy Times: Are there any ongoing or planned studies to further explore cilta-cel’s potential in different patient populations or treatment settings?
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Popat: Yes. So absolutely, there are a number of different studies currently running, looking at cilta-cel. I want to highlight 2 studies in the front-line; CARTITUDE-5, which was looking at patients who are not transplant eligible that were randomized to receive VRD and len maintenance compared to VRD and cilta-cel, and then the CARTITUDE-5 study for newly-diagnosed transplant-eligible patients, which is a head-to-head comparison against dara-VRD compared to dara-VRD, followed by cilta-cel. These are clearly looking at 2 big populations in the frontline setting, which is a natural place to move after the second line setting.
Pharmacy Times: How can pharmacists educate themselves and counsel patients on the benefits of cilta-cel, especially for len-refractory patients?
Popat: I think it's very important that pharmacists are aware of the headline data with CARTITUDE-5, which demonstrates the improvement in PFS, but also an improvement in OS when receiving cilta-cel. I think pharmacists also, as well as the strong efficacy data, which ties up with the MRD data I'm presenting, need to understand the toxicity profile with cilta-cel. Namely, they need to understand the CRS phenotype, the ICANS data that is available, but also some of the other non-ICANS neurotoxicity, and the secondary malignancy rate. It's about trying to marry up that risk profile with a benefit profile when counseling that patient.
Pharmacy Times: Is there anything else that you would like to add?
Popat: A key thing, I think, is about the deliverability of these novel therapies to patients and to make sure that they understand the toxicity profile. Day in, day out in my clinics, when I talk to patients about novel therapies, they are often concerned about the toxicity profile, and thereby foregoing what could be an extremely effective treatment in place of a less effective treatment. My take home message is that I want people to be able to deliver the information that we're hearing, the exciting information that we're hearing at ASH, but also to be able to deliver that in a patient-friendly way, understanding the toxicity profile, to make sure that they are really accessing the treatment that they should, too.
