Sequencing CAR T and Bispecifics for Multiple Myeloma: Tyler Sandahl, PharmD

Tyler Sandahl, PharmD, a clinical pharmacist at Mayo Clinic, explains that sequencing novel multiple myeloma therapies with CAR T-cell therapy is generally prioritized first for eligible patients, while bispecific antibodies are reserved for later lines or for patients unable to tolerate CAR T.

Tyler Sandahl, PharmD, a clinical pharmacist at Mayo Clinic, explains that FDA approval criteria are currently the primary drivers in sequencing novel therapies for multiple myeloma, even when providers might prefer to use an agent earlier. In this interview with The American Journal of Managed Care® (AJMC®), Sandahl notes that institutional practices vary, with some centers using CAR T for all eligible second-line patients, while others reserve it for those with higher-risk disease.

When it comes to sequencing between CAR T and bispecifics, the current approach is to prioritize CAR T-cell therapy first for eligible patients, saving bispecifics for later. However, patient fitness and comorbidities play a crucial role. For patients who are not suitable candidates for CAR T-cell therapy due to frailty or other health issues, bispecific antibodies become a viable option. While both therapies have similar toxicity profiles, bispecifics generally present less severe toxicities, making them a more feasible option for patients who may not tolerate CAR T. She hopes for clearer sequencing guidelines and even a cure within the next 5 to 10 years to better manage the rapid influx of new treatments and improve patient outcomes.

This transcript was lightly edited for clarity.

Transcript

AJMC: With the increasing array of novel therapies for multiple myeloma, including CAR T-cells and bispecific antibodies, how do you approach the complex decision-making around sequencing these agents? What factors are most critical in guiding your recommendations?

Sandahl: A lot of that right now ends up being dictated by the FDA approval criteria. Even if providers want to use a bispecific in an earlier line of therapy, which we've certainly had patients come up where they would like to do that, your hands are tied by where it falls in the guidelines and where the FDA indication lies, because right now for the bispecifics, it's after 4 prior lines of therapy. They have to have been exposed to an IMiD [immunomodulatory drugs] proteasome inhibitor and an anti-CD38 monoclonal antibody. If you give it to them outside of that setting, you risk it not being paid by their insurance.

Whereas, now CAR T is approved in the second line, and so it depends on who your providers are and what institution you're at, whether they're using CAR T for everyone in the second line, or if they're just giving it to patients with higher-risk disease.

I think right now, in terms of sequencing with CAR T and bispecifics for patients who are considered eligible for CAR T, we've been trying to get them to CAR T first and then reserving those bispecifics for later on. There are a lot of patients who really aren't fit enough to go to CAR T, so if they're not candidates for CAR T cell therapy due to frailty or other comorbidities, that's when we consider getting them on a bispecific because of the toxicities.

They have similar toxicity profiles, but they don't tend to be as severe with the bispecifics, and so patients who wouldn't necessarily be considered a candidate for CAR T might be more fit to do bispecific therapy and still have good outcomes.

AJMC: Given the rapid pace of research in multiple myeloma, particularly in the CAR T and bispecific antibody space, how do you envision these future developments impacting practices and the care of patients with multiple myeloma over the next 5 to 10 years?

Sandahl: I would love to see more clear guidance on sequencing because I feel like every time we get comfortable with something or there's a new therapy, and we think, “Okay, you start with your quadruplet (quad) therapy and then they go to transplant, then do this” but now we consider “What if they start with a quad and then go to CAR T but there are studies looking at bispecifics in the upfront setting”.

When you look at the waterfall of information, every time you get comfortable with something, a new study comes out, and we have to kind of shift our practice. I haven't been working in the myeloma space all that long. I think I started in 2018, and it's gone from doublets to triplets, and then all of a sudden, daratumumab (Darzalex) frontline was the big thing, and now that's old news. I feel like every year there's something new that comes out, something shifts, and keeping up with the information and the new drug approvals in itself is a challenge.

I think in the next 5 years, ideally it would be great to have a better grasp on this as upfront second line, how a patient should progress through therapy, and then leave the relapse refractory setting for us to tease out later, keep introducing new drug classes, and targets.

I think it'd be great to have a cure for myeloma. Is that something we'll see in the next 5 to 10 years? I don't know, but to see even longer overall survival, progression-free survival, on each subsequent line of therapy, because we're really honing in on that. Improving survival overall is crucial, but also finding strategies to decrease these toxicities that we can see with things as well.