Teclistamab's Growing Case for Earlier Use in Myeloma: Roberto Mina, MD

Teclistamab, a B-cell maturation antigen (BCMA)–targeting bispecific antibody, has demonstrated compelling efficacy in relapsed/refractory multiple myeloma (R/R MM), with data suggesting its potential extends beyond later-line monotherapy. In an interview with The American Journal of Managed Care^®(AJMC^®), Roberto Mina, MD, associate professor at the Winship Cancer Institute of Emory University and principal investigator of the MajesTEC-9 trial (NCT05572515), discussed the mechanism of action underlying teclistamab's activity, the design and rationale of MajesTEC-9, and the trial's topline efficacy results.

He also highlighted the significance of MajesTEC-9’s patient population—heavily pretreated individuals refractory to CD38 antibodies and lenalidomide—and explained why the trial's findings could reshape treatment decisions as early as first relapse.

This transcript has been lightly edited for clarity.

AJMC: What aspects of teclistamab’s mechanism of action may help explain its activity in R/R MM, both as monotherapy and in combination regimens?

Mina: Teclistamab is a bispecific antibody that brings, basically, the T cells of the patient in close proximity to the malignant cells. In this case, particularly malignant plasma cells. It binds to BCMA, which is a key antigen expressed by malignant plasma cells, and it has been demonstrated, as bispecific antibodies in general and also in other diseases, to be a highly effective platform. The efficacy of teclistamab has been demonstrated in the MajesTEC-1 study [NCT04557098], which is the pivotal study that led to the current approval of teclistamab as a monotherapy for patients with R/R MM in later lines, patients with 4 or more prior therapies. But we also have some data about the use of teclistamab in other settings, in earlier lines for relapsed/refractory [disease], even in newly diagnosed settings that have shown really high efficacy.

But I would also say, and I would like to underline also, its safety profile. The safety profile is a key component of teclistamab, and also the logistics around the administration of bispecific antibodies that are not only highly effective [and] safe, but also easy to administer and complement other immunotherapies that are maybe more complex to administer, such as CAR [chimeric antigen receptor] T-cell therapy.

AJMC: Can you briefly outline the design of the MajesTEC-9 trial, including the patient population and the key primary and secondary end points?

Mina: MajesTEC-9 is a phase 3 randomized study that is comparing teclistamab as a monotherapy, administered until progression, to a standard-of-care treatment that could be, at physician's discretion, either a doublet with carfilzomib or a triplet with bortezomib, pomalidomide, and dexamethasone. Both are approved standard-of-care regimens for the treatment of R/R MM worldwide.

The study randomized patients in a 1:1 fashion to receive either teclistamab or the standard of care. Patient had to be patients with relapsed/refractory myeloma, 1 to 3 prior lines of therapy, and all patients had to be exposed to daratumumab or another CD38 antibody and lenalidomide, an immunomodulatory drug. In fact, the majority of these patients were actually refractory to either or both agents. End points are progression-free survival [PFS]; this is the primary end point. Secondary end points are overall survival (OS), complete remission rate, and patient-reported outcomes.

Why is MajesTEC-9 so important? One reason is the population of patients enrolled. Because, as mentioned, patients had to be exposed to a CD38 antibody and lenalidomide, and we know now that these 2 agents are pivotal in the treatment of newly diagnosed myeloma patients. They have extended significantly the PFS and OS of these patients. But we know at the time of the relapse, most of these patients will be, and their disease will be, resistant to either or both drugs. This makes the treatment choice of a salvage regimen as early as a second line, or first relapse, quite challenging, and so MajesTEC-9 and teclistamab really tackles this issue.

AJMC: What are the key efficacy findings from MajesTEC-9 reported to date?

Mina: We know that MajesTEC-9 met its primary end point. MajesTEC-9 was able to show a significant improvement in terms of PFS, with an HR of 0.29, meaning a 71% reduction in the risk of progression or death. Along with the PFS advantage, there is also an OS advantage, which means that patients who were randomized and treated with teclistamab, as opposed to the standard of care, had a 40% reduction in the risk of dying compared with the standard of care. Not only was teclistamab shown to be more effective in delaying the progression, but also in reducing the risk of death that we have seen compared with the standard of care.