How Teclistamab Is Rewriting Second-Line Myeloma Care: Roberto Mina, MD

As MajesTEC-9 data (NCT05572515) continue to reshape the treatment landscape for relapsed/refractory multiple myeloma (R/R MM), questions are turning to how, and how early, teclistamab should be deployed in clinical practice. In the second part of his 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 MajesTEC-9, explores the clinical implications of the trial's landmark findings. Mina discusses what a 71% reduction in progression risk means for patients who have exhausted frontline options, how MajesTEC-9 positions teclistamab for earlier use, and how clinicians should weigh monotherapy vs combination approaches in the second-line setting, drawing on data from both MajesTEC-9 and the combination-focused MajesTEC-3 trial (NCT05083169).

Revisit part 1 of this interview.

This transcript has been lightly edited for clarity.

AJMC: Given the 71% reduction in the risk of disease progression or death seen with these latest results from MajesTEC-9, how clinically meaningful are these findings for patients who have already progressed on standard-of-care therapies?

Mina: The results that we have seen so far with MajesTEC-9 underline the importance of [teclistamab’s] early use and early access to it general, I would say. This is complemented by also other studies, such as MajesTEC-3, where teclistamab was proven superior to the standard of care in combination with daratumumab, so CD38 antibody but also CAR [chimeric antigen receptor] T-cell therapy. In general, all of these studies, and MajesTEC-9 reinforces this message, suggest that earlier use should be a new standard of care, as it has been proven extensively across all these studies. A benefit in terms of progression-free survival [PFS], but also in terms of overall survival [OS] over standard of care, meaning that when we use these immunotherapeutic platforms, and teclistamab is one of these agents, they perform better in terms of PFS, in terms of OS. So, I think that the first message is that the earlier the use, the better with such agents.

AJMC: How do the MajesTEC-9 data, which included patients treated after 1 to 3 prior lines, inform teclistamab’s potential role earlier in the disease course?

Mina: The results of the MajesTEC-9 study are extremely important because [they] will allow us to use teclistamab in an earlier line, as opposed to the current approval. We now know, based on the MajesTEC-1 study [NCT04557098], that teclistamab is highly effective in patients with R/R MM heavily pretreated. But we would like to use this agent early on, also because we know that now with the combination of several agents already in the first line, patients become very quickly exposed and refractory to most of the agents that are, let's say, considered standard of care. MajesTEC-9 allows us to bring forward and use teclistamab earlier in the course of the treatment of patients. It allows us to intercept that patient population, which is very relevant in the clinical practice, because it's that patient population that is relapsing and becoming refractory to lenalidomide and a CD38 early on, as early as the first line of treatment. This particular study will allow us to treat patients with a highly effective regimen, with a different mechanism of action and a different target early on.

AJMC: Based on the available data, what factors should clinicians consider when deciding between teclistamab monotherapy and combination approaches in the second-line setting?

Mina: We now have 2 studies that have demonstrated the efficacy of teclistamab, either as a monotherapy, MajesTEC-9, or in combination, MajesTEC-3, with a CD38 antibody with daratumumab. Both studies have demonstrated efficacy in terms of PFS and OS, as opposed to the standard of care, as early as the second line of treatment. The first message is that these studies have established teclistamab as a new standard of care, either as a monotherapy or in combination. The studies have differences, and we must acknowledge that: differences in terms of patient population, particularly exposure to previous agents, such as exposure to daratumumab, its refractoriness, and exposure to lenalidomide as well. We will see, when the data from MajesTEC-9 will be fully available, potential other differences. I think these studies are right now complementary, and we need further data to really understand who is the ideal patient for the combination [and] who is the ideal patient for the monotherapy. But I think that generally speaking, the good news is that we have a very robust platform, which is that of teclistamab, that of a BCMA [B-cell maturation antigen]–targeting bispecific antibody as early as a second-line treatment.

I would like just to remark that with these positive results, we clinicians who cure myeloma and take care of myeloma patients will really have the opportunity to have, with both MajesTEC-9 and MajesTEC-3, the possibility and the opportunity of using a drug that is not only highly effective but has a very well-established safety profile that has been confirmed throughout the studies and is also readily accessible to patients. This allows, basically, clinicians and patients to choose and to tailor treatment according to not just the disease characteristics, which are certainly very important, but also according to patients’ preference and access. We now have a plethora of drugs that are highly effective, and this really enriches the portfolio of myeloma treatment. This is only good news.