Making Bispecific Therapies Work in Community Settings

In his previous interview, Ajai Chari, MD, University of California San Francisco, discussed the primary operational challenges health care systems face when they aim to implement chimeric antigen receptor (CAR) T-cell therapies into their practice. As CAR T-cell therapy has proved a valuable treatment option for patients with multiple myeloma, so too has the advent of bispecific therapies.

However, as Chari points out here, bispecific therapies come with their own set of challenges, which include the need for comprehensive training to ensure providers are equipped to manage potential adverse events, adequately monitor their patients, and ensure these interventions remain accessible.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Can you speak to the biggest operational challenges for bringing bispecific therapies to the clinic, and how health care systems can better streamline their adoption?

This is the opposite of CAR T because it really belongs in the community. I've always said that no one with relapse/refractory myeloma who's eligible for bispecifics should be denied a bispecific. When the drugs were first approved, who got it at my institutions? People who couldn't get it in a study: heart failure, dialysis, CNS [central nervous system] myeloma. There was no patient that I wouldn't feel comfortable giving a bispecific to because it has a rapid onset of activity: 1 month. The remissions or PFS [progression-free survival] lasts up to a year. And the side effects are manageable, because you just stop the drug.

I've often made the analogy that CAR Ts are like a Rolls-Royce or Bentley, and bispecifics are Toyota Corollas. Toyota Corollas make the world go round, and that's what's number 1 most-sold car in the world. The Bentleys are great if you can get it. But let's face it, in the US, only 20% of auto[logous] transplant patients eligible for auto transplant get it, and CAR Ts even more restricted and more expensive, so the vast majority of patients aren't going to get a CAR T.

But the vast majority of patients can get a bispecific. And what people need to remember is that we now have, I think at last count, 9 bispecifics approved in oncology and hematology. This is the wave of the future, and community doctors either need to get on board or they'll get left behind. More importantly, their patients will get left behind because bispecifics today are like the monoclonals of 30 years ago. Initially, when rituximab [Rituxan] and daratumumab [Darzalex] came around, everybody was concerned about infusion and related reactions and long appointment times, and we got over that. Now, no one bats an eye. We're going to get there, but we’re in a very steep learning curve that we need to do this.

I think the operational challenges here are, first and foremost, training in myeloma—that bispecifics have a REMS program—a risk evaluation mitigation strategy. The providers need to be trained [and] the facilities need to be trained. Step-up doses need to be done to avoid the side effects called CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity syndrome]. That can either be done in academia and then the patients go back to the community, or it can be done by community entirely.

But it is a steep learning curve if you've never dealt with these kinds of side effects, and the label has that patients need to be monitored for up to 48 hours. How are you going to do that in a community setting? Are you going to do it as all-admission, in which case, who's covering these patients? Are you going to do it as a hybrid, where you give the drug in outpatient, you admit them for the monitoring? Or you do it all outpatient? And so those are all things that we're trying to work out.

For bispecifics to truly have the impact that they can, they need to be given in the community because the frail, elderly patients aren't coming to academia to get the products, and they will have a huge impact on patient outcomes if it can be done in the community.