Dr Binod Dhakal: The Importance of Patient Monitoring With Cilta-Cel Treatment

In part 2 of our interview with Binod Dhakal, MD, he addresses how the findings from the CARTITUDE-4 study help to advance the clinical understanding of ciltacabtagene autoleucel (cilta-cel [Carvykti]; Janssen/Johnson & Johnson and Legend Biotech) and the importance of vigilance and education on the treatment’s adverse effects.

Dhakal is associate professor, Division of Hematology and Oncology, Medical College of Wisconsin, and lead investigator of the CARTITUDE-4 study of cilta-cel for patients with relapsed/refractory multiple myeloma (RRMM) who have received at least 1 prior line of therapy.

The chimeric antigen receptor (CAR) T-cell therapy was approved by the FDA as a second-line treatment for RRMM on April 5. Watch part 1 of our interview with Dhakal here.

Transcript

How do key findings from the CARTITUDE-4 trial contribute to our understanding of cilta-cel’s efficacy and safety?

As I said prior, the key finding from CARTITUDE-4 is that cilta-cel, or Carvykti, significantly prolonged progression-free survival, which is the primary end point, compared with the standard of care. At a median follow-up of about 16 months in the study, the median PFS, or progression-free survival, was not reached in the cilta-cel arm in the study compared to about 11 months in the standard-of-care arm. The standard-of-care arm performed exactly [as] expected.

Now this is important because the data show the superiority of cilta-cel over effective standard-of-care therapies that are often used in real-world practice in patients especially with lenolidamide-refractory multiple myeloma. It is also important because this is the first study to look at a CAR T [chimeric antigen receptor T-cell] therapy in multiple myeloma patients after the first relapse and compared to the standard of care.

In addition to the efficacy that we saw, what we also observed, as I mentioned before, is a lower incidence of CAR T–related adverse events like CRS [cytokine release syndrome], ICANS [immune effector cell–associated neurotoxicity syndrome], and neurocognitive treatment-emergent adverse events when compared to patients in late relapses, especially when tested in the CARTITUDE-1 patient.

It all suggests that it is not only effective, but it is safe when used in other lines of treatment. So I think these key findings are very important and can be an important tool when we deliver this treatment option in patients in that space, with 1 to 3 prior lines of therapy.

What are clinicians’ top concerns when addressing potentially life-threatening adverse effects from cilta-cel?

Usually I can group them all into the adverse events, also called CAR T–related adverse events. They can happen right after administration of the CAR T or can happen later as well, so it's very important that the patients, the caregivers, and the providers who are offering this treatment are fully aware of these adverse events, that the risk is there. They should be fully educated around when it is likely to happen, how long the patients should be monitored, and what are the subtle signs of this delayed neurotoxicity that could happen so that they are aware and really can get the intervention early. Because we saw that if you have early intervention, this really doesn’t have a long-lasting morbid effect on the patient.

This would be discussed in detail when I see a patient in the clinic and when I offer the therapy like CAR T therapy, not only cilta-cel but for any CAR T therapy for that matter. I usually go through all the side effects that would happen with this therapy with the patient and the caregiver and the importance of monitoring and following that. It's very important we discuss that in detail because the caregiver education is also very important. They are the ones who could identify some of these toxicities when taking care of the patients, and as you know, for some period of time after the treatment they need to be monitored very closely and they need to be seen.

So at that period of time, the education of the caregiver is very important. But at the same time, we also look at into the context of how significant those toxicities can be and how they could impact the life of the patients. As I mentioned before, the rates and grades of these toxicities are much lower in CARTITUDE-4 than CARTITUDE-1. So that suggests one important aspect of the treatment: If you give this treatment in patients with low disease burden, which are majority of patients in the early lines, then the likelihood of having these side effects is much lower—so I think that is of key importance. And when you look at the whole aspect of the risk/benefit profile, I think treatment with Carvykti favors the risk/benefit profile. It’s still effective and good treatment for those patients for that treatment line.

As we move forward with CAR T in early lines, I think there will be more patients who probably are going to get the CAR T at a lower disease burden and in real life as well. And then I think we are going to have lesser grades and rates of the toxicities. At the same time with the ongoing research, we'll be able to find out how to improve these toxicities, how to prevent, and how to treat them more effectively so that these toxicities don’t become a real problem down the road.