With New Developments in CAR T Therapies, Progress is Being Made for Patients With Multiple Myeloma

From the first approved CAR T therapy for multiple myeloma, to the recently-approved ciltacabtagene autoleucel, significant steps have been taken.

In an interview with Pharmacy Times, Yi Lin, MD, PhD, discussed new developments with CAR T therapies for the treatment of multiple myeloma. From idecabagene vicleucel (Abecma), the first approved CAR T therapy for multiple myeloma, to the recently-approved ciltacabtagene autoleucel (Cilta-Cel), Lin said significant steps have been taken.

Q: Abecma was the first CAR T therapy approved for multiple myeloma, and Cilta-Cel is the latest. Can you discuss how Abecma works and how it differs from Cilta-Cel?

Yi Lin, MD, PhD: So, idecabagene vicleucel, or Ida-Cell, or the name is Abecma, has now been available in standard of care practice for a little over 1 year. This particular CAR construct, CAR T therapy, is also an autologous product made from patients’ own T cells, and it's also prescribed as a one-time treatment. So really, that's I think the most exciting thing about CAR T right now, is it’s a one-time treatment with no maintenance follow up. They are given as essentially a fixed dose, not weight-based, 300 to 460 million CAR T cells per dose. And that's totally dependent on how many of those cells can be manufactured on the patient's own T cells.

In the registration study that led to its approval—again, this is also a very late, relapsed/refractory patient population—the median line of prior therapy was also 6. And again, it was one time dosing. [We saw a] very impressive response—73% of those patients responded, 33% of those patients had deep response. And on that study, we've had longer follow up. So, we are seeing that the median progression-free survival is over 8 months, 8.8 months to be exact, for the entire treated population. But if you look at patients who were able to get that higher dose in the range, or patients were able to achieve deep response, the median progression-free survival is much longer, closer to a year. So, I think in the current landscape of myeloma treatment, this is a very impressive treatment option that's available for our patients.

Q: What is pharmacists’ role in CAR T therapies?

Yi Lin, MD, PhD: Pharmacists are an integral member of our CAR T teams. They play a critical role. From the very first appointment, where we are evaluating patients and considering their eligibility, planning to go towards that collection of the patient's own cells, pharmacists are very much involved in looking at what was the patient's most recent exposure to the prior salvage treatment, [and] the washout period, because this directly impacts the health of the cell that's collected and the likelihood for successful manufacturing. They are, of course, involved in terms of any bridging management that is needed, trying to optimize the care and preserve organ functions from the drugs that are given to improve the chance that the patients can make it to CAR T dosing. Most of our patients will need a line placement for the cell infusion and there may be need to manage anticoagulation around that time. And then, of course, once we actually get to the CAR T treatment, that is always given with the lympho-depletion chemotherapy drug. And in our myeloma patient population, they don't always have normal kidney functions, for example. So, pharmacists work very closely with our team to look at the appropriate dosing adjustments for the lympho-depletion chemotherapy. Part of the REMS requirements by the FDA, the risk evaluation mitigation system requires that for all patients, prior to getting those with CAR T, that we have reserved for them the first line treatment for cytokine release syndrome, which is tocilizumab IL-6 receptor blockade, so it's ready to go when we need it and there's no delay. And so pharmacists are the essentially the keeper to ensure that we have adequate supplies, and it's ready to go for patients, as well as if there's a need to escalate the management, all the different drugs that are used, including in the acute monitoring periods, really looking very carefully over all the other medication that may be needed for symptom management to also make sure that they are not masking anything we need to monitor, from the standpoint of infection, cytokine release syndrome, and neurologic symptoms. And then moving on, during that time and moving beyond that for even longer-term follow up, antimicrobial prophylaxis and some of the other medication management considerations when you're working with a living drug.

Q: Is there anything you would like to add?

Yi Lin, MD, PhD: Absolutely. So, I think right now what we're basically telling everybody is that the CAR T is a very individualized treatment that is made from patients’ own cells. There's a lot of logistics in getting the patient through to treatment, and so we definitely encourage everybody who's taking care of these patients to be thinking early about their referral, and if the patient might be a candidate for CAR T, and any considerations in their management to improve the odds to get the patients to treatments. And, as I mentioned at the beginning of the interview, there's a lot of investigations going on for next generation CAR T and innovative CAR T. And so, I think as we learn about these CAR Ts, for example, those that may be more rapidly manufactured or allogeneic platform, we may start to learn what are some of the unique side effects or considerations for management? And I think that's very relevant for the pharmacist practice to understand as these things evolve. How does their management change with the new treatment modalities?