In an interview with Pharmacy Times®, Rakesh Popat, MBBS, PhD, associate professor at University College Hospital in London, United Kingdon elaborates on the data he is presenting at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition that showcases the increase in minimum residual disease (MRD) negativity in patients with lenalidomide (Revlimid; Bristol Myers Squibb)-refractory multiple myeloma (MM) after being treated with ciltacabtagene autoleucel (cilta-cel).
Popat explains how pharmacists should be aware not only of the topline data surrounding MRD negativity, but be prepared to deliver the information regarding the safety profile and benefits of cilta-cel in a patient-friendly way. Additionally, he emphasizes the importance of the patient being able to access cilta-cel treatment if they present as a candidate for disease improvement.
Pharmacy Times: What are key points of this analysis of MRD negativity that pharmacists and treatment providers should know about?
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?
The 66th ASH Annual Meeting and Exposition takes place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can follow our continuing coverage here.
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.
