At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Robert M Rifkin, MD, US Oncology Research, Rocky Mountain Cancer Centers, Denver, Colorado, discusses a study on the outpatient administration of step-up doses of BCMA-targeting bispecific antibody teclistamab, including whether the use of prophylactic tocilizumab can reduce the incidence and severity of cytokine release syndrome (CRS).

Transcript:

Hello, my name is Dr. Robert Rifkin. I'm a medical oncologist at Rocky Mountain Cancer Centers in Denver, Colorado. It's my honor to review the poster that we're presenting here at this 2023 ASH. It's a trial in progress poster, which is a little bit unusual, but what we hope is that by doing the study outlined in the poster will cause a big practice changing event in the area of administration of bispecific antibodies. In this particular study that we're now just barely starting, we're trying to minimize cytokine release syndrome (CRS) and other nervous system complications from bispecific antibodies. The approach here will be a little bit different in that we're going to give teclistamab, according to the FDA label, but the thing that we hope will practice change is to administer prophylactically tocilizumab to decrease the incidence of CRS and [immune effector cell-associated neurotoxicity syndrome] (ICANS). In addition to that, we'll also have some steroids in the pre-med, which should further decrease that. 

The last part, which I think is very important with this particular molecule is in myeloma patients [who] have received multiple lines of therapy, all of them have an increase[d] infection risk, and this is well documented for teclistamab. The other component of the study that will make us a little bit unique [is] the administration of intravenous immunoglobulin [therapy] (IVIg) according to each center[‘s] standard of care. A lot of these heavily pretreated myeloma patients will have [immunoglobulin G] (IgG) levels of less than 400, where we know there's a significant increase in the risk of infection. That'll also be an important part of this study. Not only do we hope to mitigate, decrease the risk of CRS, and keep people out of the hospital, but we also want to aggressively treat and try to prevent the infections that are a well-known complication of late-stage myeloma patients, and certainly those receiving bispecific antibodies, especially teclistamab. The study is underway now, [and] we do have some predetermined brief holds after we've accrued 5 in 10 patients for a safety review. In addition, we'll be doing extensive [pharmacokinetic/pharmacodynamic] (PKPD) [modeling] to make sure that giving prophylactic tocilizumab doesn't in any way decrease the efficacy of teclistamab. It's a little bit unique in that area, but then once those first 10 patients are done, we'll open at a considerable number of centers and hope to reach a target of 50 patients very quickly.

Source:

Rifkin RM, Sharman JP, Fowler J, et al. A Phase 2 Study to Evaluate Outpatient Administration of Teclistamab, a BCMA-Targeting Bispecific Antibody, in Patients with Multiple Myeloma. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 3374