Weighing Bispecific Antibodies Against CAR T Cells in Multiple Myeloma

As BCMA-directed T-cell–redirecting therapies expand in multiple myeloma, patients and clinicians increasingly face a choice between a bispecific antibody, requiring more chronic, ongoing treatment, and CAR T-cell therapy, a single infusion with more front-loaded intensity.

Hans Lee, MD, director of Myeloma Research at Sarah Cannon Research Institute in Nashville, Tennessee, spoke with CancerNetwork^® about how he weighs that trade-off with patients and what has changed in managing bispecific-related toxicity.

Transcript:

CancerNetwork: How do you weigh the trade-off between a bispecific antibody’s more chronic, ongoing treatment burden vs CAR T-cell therapy’s single-infusion, front-loaded intensity when a patient is choosing between those classes of drugs?

This is a conversation I have with patients every day. The thought is that patients should get some form of BCMA T-cell–redirecting therapy as early as possible in the relapsed/refractory setting, either a BCMA bispecific antibody or BCMA CAR T-cell therapy, whichever is available to the patient. There are trade-offs: a single infusion of CAR T-cell therapy [requires] a lot more upfront activation energy needed to get a patient to CAR T, including apheresis, manufacturing, infusion, and monitoring, especially in the short term after infusion. I would also say that while CAR T-cell therapy is considered one-and-done, there is still a lot of supportive care needed afterward. It is important to be realistic with patients in that discussion, including infection monitoring, intravenous immunoglobulin [IVIG] after CAR T-cell therapy, cytopenias that can occur, and other issues. It is important to recognize that there are still additional steps involved in the post-CAR T setting that are mainly supportive care.

With bispecific antibodies, since they are off-the-shelf, they can be administered right away, so the activation energy to get a patient started is much less than with CAR T-cell therapy. There still needs to be a plan and a process in the local practice setting for monitoring early potential adverse events, mainly cytokine release syndrome [CRS] and, rarely, immune effector cell-associated neurotoxicity syndrome [ICANS]. The incidence and severity of CRS is lower with bispecific antibodies compared with CAR T-cell therapy. That’s one nice thing. We are also learning a lot more about how to mitigate these early adverse events, such as giving prophylactic tocilizumab [Actemra] prior to the first step-up dose, which has decreased the incidence of CRS from 50% to 70% down to less than 10% to 15%, enabling outpatient step-up dosing.

In the long term, infection monitoring is critical with bispecific antibodies, and giving monthly IVIG is important. We are also learning that treatment until progression is probably not the path forward; we are looking at fixed-duration treatment approaches, giving perhaps a year or 2 of bispecific antibody-based therapy. [Because] these therapies can elicit deep and durable responses quickly, it is probably not necessary for patients to stay on therapy forever, as has been the historical paradigm in myeloma.